Manejo de Depresión en Demencia y Enfermedad de Alzheimer

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  • It was believed that in elderly people with so-called depressive pseudodementia, cognition and function could be entirely restored to normal if depression was treated. However, this concept has been progressively abandoned since cognitive dysfunction may not be totally reversed by antidepressant
    treatment and more than 40% of people with pseudodementia eventually develop dementia (Alexopoulos GS, Meyers BS, Young RC, Mattis S, Kakuma T. The course of geriatric depression with ‘‘reversible dementia’’: a controlled study. Am J Psychiatry 1993; 150: 1693–9. Kral VA, Emery OB. Long-term follow-up of depressive pseudodementia of the aged. Can J Psychiatry 1989; 34: 445–6.). Our results support a link between affective disorders and the later development of dementia, especially in men and in people with recurrent depressive disorder (Kessing LV, Andersen PK. Does the risk of developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder? J Neurol Neurosurg Psychiatry 2004; 75: 1662–6. Brommelhoff JA, Gatz M, Johansson B, McArdle JJ, Fratiglioni L, Pedersen NL. Depression as a risk factor or prodromal feature for dementia? Findings in a population-based sample of swedish twins. Psychol Aging 2009; 24: 373–84.).Therefore cognitive dysfunction in such patients should not be disregarded as a minor phenomenon. Clinical monitoring of cognition may be warranted, for at least
    a subset of patients.
  • Late-life depression (LLD ) is also often more chronic and difficult to treat to remission than mid-life depression, an observation that has been attributed in part to medical co-morbidity and cognitive dysfunction (Blazer, 2003). For these reasons and others, LLD is associated with significant mortality (including due to suicide), health care usage, physical disability, and functional decline (Beekman et al., 2002; Bruce et al., 2004; Steffens et al., 2006).
  • Greater severity of depressive symptoms at baseline was associated with a higher risk of developing dementia and Alzheimer’s disease. Moreover, a large case register-based cohort study in Denmark showed that the number of depressive episodes leading to admission increased the risk of being readmitted with a diagnosis of dementia. However, the difference was only significant when individuals with one depressive episode were compared with people who had more than four episodes (HR = 6.16, CI 95% 1.39–27.22).41 Similarly, in a community cohort with a long follow-up period (median 23.6 years), Dotson
    et al reported a dose–response relationship between the number of what they called ‘episodes of elevated depressive symptoms’ and the risk of developing dementia. Nonetheless, one study found that participant-reported duration of depression was not predictive of Alzheimer’s disease (OR = 1.01, 95% CI 0.88–1.15) or dementia (OR = 1.04, 95% CI 0.97–1.11). In this study, however, it was not clear what was measured with this self-report (for example either total duration of depressive episodes, or duration of present or last episode).
  • We found that late-life depression increases the risk of incident all-cause dementia and, more specifically, of both vascular dementia and Alzheimer’s disease. After including only those studies that reported risk measures adjusted for multiple confounders, the strength of the association between late-life
    depression and the risk of all-cause dementia, Alzheimer’s disease and vascular dementia was reduced, but still statistically significant. Additionally, we demonstrated, for the first time, that the risk of vascular dementia is significantly higher than the risk of Alzheimer’s disease in older adults with late-life depression in population-based prospective cohort studies.
    Findings from other studies
    Our results are in line with a recent report that showed an increased risk of all-cause dementia, vascular dementia and Alzheimer’s disease in participants with mid- and late-life depression in a retrospective analysis of 13 535 elder participants followed on the Kaiser Permanente Medical Care Program of
    Northern California. We found a less strong association between late-life depression and Alzheimer’s disease compared with Ownby and colleagues
    for cohort prospective studies (Ownby study: OR = 1.90, 95% CI 1.55–2.33 v. present study: OR = 1.65, 95% CI 1.42–1.92), although this difference is not statistically significant (X2 = 1.81, d.f.= 1, P= 0.17). Methodological differences between the two studies may help to explain such differences. First, the present meta-analysis focuses on the risk of dementia among individuals with late-life depression in contrast to the Ownby meta-analysis, which included studies of mid- and late-life depression. We included a larger number of population-based prospective cohort studies (23 v. 8 studies), yielding a homogeneous pool of studies and a much larger sample of older adults. In addition, the combination of retrospective, case–control and prospective studies
    and the inclusion of mid- and late-life depression cases in Ownby’s study led to high heterogeneity in the analysis, possibly inflating the association between depression and Alzheimer’s disease. Finally, we evaluated the risk of all-cause dementia and, more specifically, of vascular dementia in addition to and
    separately from Alzheimer’s disease. Thus, the current results go beyond and extend the findings from this previous meta-analysis, being specific to older adults and permitting broader generalisation to the population of older adults with major depression.
    Vascular dementia
    This is the first meta-analysis to show that late-life depression increases the risk of vascular dementia and that the risk of vascular dementia is greater than the risk of Alzheimer’s disease in these individuals. In general, late-life depression is associated with poorer general health and, in particular, has a strong association with higher burden of cardiovascular and cerebrovascular disease. Thus, our finding of an increased risk of vascular dementia in individuals with late-life depression provides additional evidence of a negative interaction between vascular pathology and late-life depression. Moreover, vascular disease
    co-occurs with Alzheimer’s disease at a very high rate and may moderate when clinical Alzheimer’s disease symptoms appear, raising the possibility that in the original studies some cases of diagnosed Alzheimer’s disease are indeed cases of mixed dementia (Alzheimer’s disease + vascular dementia), stressing the importance of vascular pathology and poor outcomes in late-life depression. Nonetheless, the finding of increased risk of vascular dementia, and of significantly higher risk as compared with Alzheimer’s disease, should be viewed with caution, as it is based on only five studies. Also, most studies did not directly compare the risk of Alzheimer’s disease + vascular dementia in participants with late-life depression, except Lenoir et al, who found that the
    risk for vascular dementia was significantly higher than for Alzheimer’s disease (P = 0.002).
  • The current literature strongly suggests that from diagnostic (Diniz et al., 2013) and neuropathological (Sweet et al., 2004) perspectives, LLD is most commonly associated with increased risk for clinical Alzheimer’s disease (AD). However, there is also evidence that non-AD neuropathological changes (such as Lewy bodies, vascular disease, and hippocampal atrophy related to hypercortisolemia) occur in individuals with LLD at greater rates than in non-depressed individuals (Schneider et al., 2007; Sweet et al., 2004).
    This figure depicts mechanisms by which depression may contribute both directly to AD pathology and indirectly, by reducing brain reserve, to the earlier appearance of clinical dementia symptoms. The figure does not, however, present a comprehensive model of all neurobiological mechanisms involved (including AD pathogenesis and various clinical outcomes), and does not depict all interrelationships among constituent parts. For example, it does not depict the possibility that in some individuals, depression may interact directly with AD causal risk factors to cause clinical manifestations of AD; in this scenario, depression may only be a risk factor in the presence of another established risk factor (Geda et al., 2006).
    The model in this figure depicts three interacting pathways, based on well-established findings that LLD is associated with hypothalamic-pituitary-adrenal (HPA) -axis dysfunction leading to elevated adrenal glucocorticoid production, as well as chronic inflammation (Butters et al., 2008). There are two
    potentially independent pathways—each involving HPAaxis dysfunction—through which depression may lead to increased risk for, or incidence of, AD. In the first, HPA-axis dysfunction may directly contribute to AD pathology, based on evidence from rodent studies (Dong & Csernansky, 2009; Rothman & Mattson, 2010). In the second, HPA-axis dysfunction in the form of hypercortisolemia may, over repeated episodes, lead to apoptosis of hippocampal cortisol receptors, resulting in hippocampal atrophy. The third pathway in the model involves depression-related chronic inflammation leading to ischemia, especially in frontostriatal pathways. The combination of hippocampal atrophy, generalized ischemia, and frontostriatal dysfunction likely lowers brain reserve, which in the context of underlying AD neuropathology hastens the clinical presentation of dementia. In this model, it is the depression-related increase in AD pathology, together with the reduction in brain reserve caused by depression associated neurotoxocity, which reduces time to expression of clinical dementia (thereby accounting for the frequently reported increased risk of cognitive decline and dementia among individuals with a history of depression).
    A detailed discussion of the literature summarizing the above-mentioned pathways is beyond the scope of this brief review. For recent work on the relationship between stress, HPA-axis dysfunction, and AD pathology in rodents, the interested reader is referred to reviews by Dong and Csernansky (2009) and Rothman & Mattson (2010). For detailed discussions of the relationship between hippocampal volume and depression, the reader is referred to publications by Videbech & Ravnkilde (2004), Janssen and colleagues (2007), and Sheline, Gado, and Kraemer (2003). Lastly, for a review of important work on the relationship between frontostriatal lesions and depression, the reader is referred to studies by Herrmann, Le Masurier, and Ebmeier (2008) and
    Krishnan and colleagues (2006).
  • Aquí, los síntomas depresivos pueden ser síntomas precoces del trastorno, lo que se ha dado en llamar ocasionalmente síntomas prodrómicos o, incluso en la terminología clásica, heraldos de la demencia.
  • The notion that depression may be a prodrome for dementia has been put forward in a number of publications. For example, depression increases the probability of conversion from mild cognitive impairment to dementia (Panza F, Frisardi V, Capurso C, D’Introno A, Colacicco AM, Imbimbo BP, et al.
    Late-life depression, mild cognitive impairment, and dementia: possible continuum? Am J Geriatr Psychiatry 2010; 18: 98–116.). This has been recently
    supported by research with peripheral biomarkers. Elderly patients with depression but without cardiovascular disorders exhibit a similar profile to that reported in patients with Alzheimer’s disease a decreased plasma concentration of amyloid (Ab) peptide Ab42 with a corresponding increase in the Ab40/Ab42 ratio.
    However, several of the studies included in our review show that the risk of developing dementia is not limited to late-life depression. In fact, a previous meta-analysis found that the interval between diagnosis of depression and Alzheimer’s disease was positively correlated with an increased risk of
    developing Alzheimer’s disease. Furthermore, many of the prospective studies presented in our review controlled for cognitive scores at baseline and in several of them depression was still found to be significantly associated with a higher risk of developing dementia. It has also been argued that depression is linked with a higher risk of developing dementia because it is a frequent reaction to the emotional losses associated with cognitive decline. In this regard, Wilson et al re-analysed the data of a cohort used to study depressive symptoms and the risk of developing mild cognitive impairment or Alzheimer’s disease and could not find an increase in depressive symptoms during the preclinical phase of Alzheimer’s disease. This suggests that the association between depressive symptoms and the latter development of Alzheimer’s disease is not due to reactive issues.
    No unequivocal evidence connects late-onset depression with Alzheimer’s disease-like pathology. Therefore, although Alzheimer’s disease pathology can start to build up very early in life, it seems far-fetched to claim that early-life depression is already a manifestation of these neuropathological changes.
    Furthermore, even in the presence of increased Alzheimer’s disease pathological changes in elderly patients with depression, other explanations besides the prodrome theory are valid. For example Rapp et al found that people with Alzheimer’s disease and a history of depression showed higher plaque and tangle formation within the hippocampus, as compared with those with Alzheimer’s disease without a lifetime history of depression. Thus, it can be argued that depression may build on Alzheimer’s disease pathology, inducing higher lesion burden. Given these contradictory results, it seems that the risk of developing dementia associated with depressive disorders is not exclusively explained by the prodrome hypothesis.
  • Clinical and epidemiologic research has focused on the identification of risk factors that may be modified in predementia syndromes, at a preclinical and early clinical stage of dementing disorders, with specific attention to the role of depression. The Panza´s goal was to provide an overview of these studies and more specifically to describe the prevalence and incidence of depression in individuals with mild cognitive impairment (MCI), the possible impact of depressive symptoms on incident MCI, or its progression to dementia and the possible mechanisms behind the observed associations. Prevalence and incidence of depressive symptoms or syndromes in MCI vary as a result of different diagnostic criteria and different sampling and assessment procedures. The prevalence of depression in individuals with MCI was higher in hospital-based studies (median: 44.3%, range: 9%-83%) than in population-based studies (median: 15.7%, range: 3%-63%), reflecting different referral patterns and selection criteria. Incidence of depressive symptoms varied from 11.7 to 26.6/100 person-years in hospital-based and population-based studies. For depressed normal subjects and depressed patients with MCI, the findings on increased risk of incident MCI or its progression to dementia were conflicting. These contrasting findings suggested that the length of the follow-up period, the study design, the sample population, and methodological differences may be central for detecting an association between baseline depression and subsequent development of MCI or its progression to dementia. Assuming that MCI may be the earliest identifiable clinical stage of dementia, depressive symptoms may be an early manifestation rather than a risk factor for dementia and Alzheimer disease, arguing that the underlying neuropathological condition that causes MCI or dementia also causes depressive symptoms. In this scenario, at least in certain subsets of elderly patients, late-life depression, MCI, and dementia could represent a possible clinical continuum.
  • Several evidences suggest that LOD is a distinctive phenomenological entity as opposed to EOD. LOD has been associated with lower rate of family history of
    depression and higher prevalence of dementia suggesting a poorer impact of genes and a higher correlation with cognitive decline (Devanand et al.
    2004; Alexopoulos 2003). In this regard, older adults with depression present with several signs and symptoms indicative of functional and cognitive
    impairment, often attributed to initial dementia. Executive function, memory, attention and processing speed seem to be the most compromised cognitive
    domains (Elderkin-Thomson et al. 2010, Rosenberg et al. 2010; Gangulli et al. 2006; Hermann et al. 2007; Rapp et al. 2005). Cognitive deficits have been
    associated with depression independently of age of onset (Bhalla et al. 2006). However, cognitive impairment is significantly greater in LOD than in EOD
    (Hermann et al. 2007; Naismith et al. 2003; Thomas et al. 2009). In addition, several studies have demonstrated that initially cognitive impairment in LOD is
    independent of dementia conditions (Bhalla et al. 2006; Gangulli et al. 2006). On the other hand LOD increases risk of mild cognitive impairment and dementia (Panza et al. 2010; Dotson et al. 2010; Saczynski et al. 2010; Barnes et al. 2006; Wilson et al. 2002). Further, Rapp et al. 2010 have demonstrated that cognitive decline in patients with dementia was further accelerated by the presence of depression. Taken together these data provide evidence for some pathophysiolocal event linking LOD, cognitive decline and dementia. Some authors suggest a common neuropathological platform based on vascular dysfunctions linking these two major geriatric pathologies (Gironi et al. 2010; de Toledo et al. 2010; Santos et al. 2009).
    Age at onset of depression (early- and late-onset depression specifiers) has also been used to explore whether depressive illness is a real aetiological risk factor for dementia, an early clinical manifestation (prodrome) or a psychological reaction to the disease process. Most of the studies evaluated only late-onset depression or late-life depression. Some also looked at early- and late-onset depression or late-life depression at the same time. However, contradictory findings undermine a straightforward conclusion, with data supporting an increased risk only for late-onset depression, early-onset depression alone or both. In the latter study, the authors went further and presented risk estimates depending on the interval (in years) between onset of depression
    and Alzheimer’s disease onset. Although the risk of developing dementia was greater for people who had a first episode of depression a few years before the onset of cognitive impairment, the risk was also significantly increased for individuals with much earlier onset of depression (25 years before the onset of
    dementia).

    Contrary to late-life depression, the association between early life depression and dementia risk is more difficult to study. It poses greater methodological challenges such as recall bias, retrospective definition of cases or the necessity for a longer follow-up period. In a recent review, Byers & Yaffe concluded
    that early-life depression is a consistent risk factor for dementia but that the results regarding late-life depression were conflicting.
    Our review does not completely support this perspective. For instance, the results from studies that evaluated both early- and late-life depression as risk factors for dementia are not consistent. This may be explained by methodological differences, especially divergences with regard to the definition of age at onset of late-onset depression. We cannot exclude the possibility that both early- and late-onset depression are related to an increased risk of developing dementia.
  • Estas lesiones denominadas leucoaraiosis reflejan cambios vasculares sobre todo de arterias cerebrales pequeñas; y el reconocimiento es estados depresivos puede ser el nexo entre depresión y demencia.
    Objective: White matter abnormalities may interfere with limbic cortical balance and lead to chronic depressive syndromes. The authors used diffusion tensor imaging to test the hypothesis that depressed elders who fail to achieve remission have microstructural white matter abnormalities in cortico-striato-limbic networks implicated in geriatric depression.
    Method: The subjects were nondemented individuals with nonpsychotic major depression. After a 2-week placebo period, those subjects who had a Hamilton Depression Rating Scale (HAM-D) score of 18 or greater received escitalopram, 10 mg daily, for 12 weeks. Remission was defined as a HAM-D score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed at a 1.5 Tesla scanner, and voxel-based analysis of fractional anisotropy was conducted using age as the covariate.
    Results: Subjects who failed to achieve remission (N=23) had lower fractional anisotropy in multiple frontal limbic brain areas, including the rostral and dorsal anterior cingulate, dorsolateral prefrontal cortex, genu of the corpus callosum, white matter adjacent to the hippocampus, multiple posterior cingulate cortex regions, and insular white matter, relative to those who achieved remission (N=25). In addition, lower fractional anisotropy was detected in the neostriatum and midbrain as well as select temporal and parietal regions.
    Conclusions: Lower fractional anisotropy in distributed cerebral networks is associated with poor antidepressant response of geriatric depression and may
    represent a neuroanatomical substrate that predisposes to this disorder.
  • Background and Purpose—There have been conflicting results involving the clinical significance of white matter changes
    in patients with Alzheimer’s disease (AD). We studied the association between the volume of white matter
    hyperintensities (WMHs) on T2-weighted images and cognitive, neurological, and neuropsychiatric symptoms.
    Methods—The subjects were 76 AD patients who had WMHs but no obvious cerebrovascular diseases. We quantified the
    volume of WMHs by using fast-fluid–attenuated inversion recovery images and whole brain atrophy by using 3D
    spoiled gradient-echo images. Effects of WMHs and brain atrophy on dementia severity, cognitive function,
    neuropsychiatric disturbances, and neurological findings were examined.
    Results—Whole brain atrophy was significantly associated with dementia severity and cognitive disturbances, as well as
    with grasp reflex and some kinds of neuropsychiatric disturbances. After we controlled for the effects of brain atrophy,
    duration of symptoms, and demographic factors, we found that WMH volume was not associated with global cognitive
    disturbances or dementia severity but was significantly associated with urinary incontinence, grasp reflex, and aberrant
    motor behaviors. Brain atrophy and WMH volume were not significantly correlated either before or after controlling for
    age, sex, education, and duration of symptoms. WMH volume was associated with hypertension, but brain atrophy was
    not positively correlated with any vascular risk factors.
    Conclusions—Our results support the hypothesis that WMHs in AD patients are superimposed phenomena of vascular
    origin. WMHs contribute to specific neurological and neuropsychiatric manifestations but not to global cognitive
    impairment, which is more closely associated with brain atrophy. (Stroke. 2000;31:2182-2188.)
  • Odds ratio > 1 indica asociacion, que las variables evaluadas estan asociadas con depresion.
    Encuentran una relacion entre LSB frontal, temporal y depresion pero no con infartos lacunares o LSB occipito-parietales. Claramente, la relacion no parece ser mediada por discapacidad fisica, calidad de vida o cognicion, lo cual sugiere un efecto directo de LSB sobre depresion.

    En un analisis separado de estos pacientes Krishnan et al (Krishnan MS. I J Geriatr Psychiatry 2006;21:983-989) demostró que las LSB profundas mas que periventriculares fueron asociadas con sintomas depresivos.
  • Objective: Several studies suggest that depression is a risk factor for development of dementia in the elderly. In a study of older depressed individuals, the authors examined both neuroimaging and genetic factors in development of dementia. The authors hypothesized that change in subcortical gray matter and white matter hyperintensity volumes would be associated with development of dementia, as would presence of an apolipoprotein E (APOE) epsilon 4 allele. Methods: The sample consisted of 161 older depressed subjects without dementia who had magnetic resonance imaging scans at baseline and at two years. Blood samples were also taken to determine APOE genotype. All participants were treated with antidepressants using a guideline based treatment algorithm. Their cognitive status was evaluated annually. A consensus panel of experts evaluated each case to determine cognitive status and assign a diagnosis.
    Results: Twenty subjects became demented over the follow-up period (5.4 years on average). Change in white matter hyperintensity volume was significantly associated with development of dementia, especially among non-Alzheimer dementias. There was a trend for change in subcortical gray matter hyperintensity volume to be associated with incident dementia. APOE genotype was not associated with onset of dementia. Conclusion: Worsening cerebrovascular disease in older depressed adults is associated with cognitive decline and dementia, particularly of the non-Alzheimer disease type. The
    association of change in white matter lesion volume and incident dementia among depressed elders extends the vascular depression hypothesis of geriatric depression to include cognitive outcomes of depression in the elderly. (Am J Geriatr Psychiatry 2007; 15: 839–849)

    We also examined low versus high values for change in WMH volumes and development of dementia using the Log-Rank test. As shown in Figure
    1, the Kaplan-Meier curves also demonstrate the significant relationship between WMH volume change and incident dementia.
  • Dementia and depression are different clinical conditions, but share common features, and can be indistinguishable in the initial disease stages. We aimed to establish whether the Peruvian version of the Addenbrooke’s Cognitive Examination (ACE-Peru) can distinguish between the cognitive profile in patients with incipient dementia and that in patients with depression. Methods: This was a cross-sectional study to assess the performance on the ACE-Peru of 193 elderly subjects (102 with dementia, 21 with depression, and 70 healthy controls). Depending on the diagnosis, there were two groups of cognitive impairment (CI) – the primary neurodegenerative (PN-CI) subtype and the secondary to depression (SD-CI) subtype – as well as a non-CI group. The area under the curve (AUC) of the receiver operating characteristic curve was determined to compare the diagnostic performance, using the diagnosis of CI as the gold standard. Results: In our sample of elderly subjects aged 59–82 years with at least 7 years of education, the ACE-Peru showed a significantly better performance than the MMSE (AUC = 0.997 vs. AUC = 0.887; p < 0.05) for the discrimination between PN-CI and SD-CI. Conclusions: The ACE-Peru is able to distinguish between the cognitive profile in patients with incipient dementia and that in patients with depression.

    The ACE showed a high precision in discriminating between PN-CI and SD-CI (AUC = 0.997; 95% confidence interval 0.99–1.00) and in discriminating between SD-CI and non-CI (AUC = 0.948; 95% confidence interval 0.90–0.99). Although the ACE had a significantly better performance than the MMSE in discriminating between PN-CI and SD-CI ( fig. 1 ), there were no similar performances in discriminating between SD-CI and non-CI ( fig. 2 ).

    Dementia is defined as the presence of CI of two or more cognitive domains [memory and other cognitive domain(s)] . Depression is defined as the absence of positive affectivity and low mood . Although dementia and depression are different clinical entities, they share common features: (1) impairment of attention and working memory, (2) changes in sleep patterns, and (3) reduction of social and work-related functionality. These problems have led to mistakes in medical practice. Thus, a study has found that at least 26 of every 100 patients were misdiagnosed as having dementia, 15 of whom were patients with non recognized depression . Similarly, it is possible that some patients with depression could be misdiagnosed as having dementia, resulting in a sub diagnosis of depression. This situation has not been previously studied. Although the cutoff value of 85 sacrifices sensitivity to maximize specificity, we believe it is appropriate because of the need to prioritize the ability of the ACE to rule out a depressive disease (suggesting a dementia disease) in every elderly patient with CI. The importance of this tool in primary health care is potentially valuable for the early detection of demented patients and their timely referral to specialized centers. Finally, the identification of patients with CI truly secondary to depressive disease is highly important for the prognosis, because appropriate treatment of depression in SD-CI patients can improve the quality of life and can even achieve a full resolution of the CI.
    The ACE-Peru is able to distinguish between the cognitive profile in patients with incipient dementia and that in those with depression, but not between the cognitive profile in patients with depression and cognitively healthy subjects. We recommended the use of 85 as a cutoff value for differentiating between these two medical conditions in elderly patients with CI. It was not possible to use the best possible instruments for the measurement processes, limiting the evaluation only to data previously obtained for other purposes. Thus, the diagnosis of depression was not reached by means of the criteria listed by the International Classification of Diseases Version 10 (ICD-10) or by the DSM-IV-TR. However, we used a depression indicator (BDI), which was validated in the elderly population and which is particularly useful in subjects with CI such as in our study population. Finally, previous studies did not assess the utility of the ACE in patients with PD for our study objectives. We propose a new use for this screening test: a comprehensive and simple tool in order to discriminate between dementia and depression in elderly patients with CI, with an easy and quick application, which might be used in primary health care. We
    recommend assessing this application at the community level in prospective population based studies.
  • El gran reto del diagnostico clinico es distinguir individuos con depresion en el contexto de demencia inicial de individuos quienes estan reportando quejas cognitivas como parte de su episodio depresivo, pues muchas de sus principales caracteristicas se superponen. De hecho, la constelacion de sintomas de concentracion disminuida, disminucion de la velocidad del procesamiento de la informacion, irritabilidad, perdida del sueno, fatiga y anhedonia que ocurre en depresion pueden parecer similares a la constelacion de perdida de memoria, agitacion, disturbio del ciclo sueno-vigilia y apatia que frecuentemente ocurren en demencia. A pesar de la similitud entre depresion y demencia, una correcta y cuidadosa historia clinica puede distinguir las dos condiciones.
  • El compromiso cognitivo puede observarse tanto en depresión como en EA, pero el patrón típico del compromiso difiere en ambas condiciones. Los pacientes con depresión típicamente exhiben deficiencias en la memoria cuando se usan test que emplean tareas de recuerdo libre de la información previamente aprendida (sin claves), mientras que las tareas que requieren el reconocimiento o con claves de ítems recientemente aprendidos son generalmente normales (Ilsley 1995, Fossati 2002). Por el contrario, durante estadios tempranos de EA, los pacientes con EA exhiben compromiso tanto del recuerdo asi como del reconocimiento de ítems previamente aprendidos (Backman, 2005).
  • Cognitive deficits that often co-occur with LLD include impairments of episodic memory, speed of information processing, executive functioning, and visuospatial ability (Baudic, Tzortzis, Barba, & Traykov, 2004; Butters et al., 2004; Elderkin-Thompson et al., 2003; Lockwood, Alexopoulos, & van Gorp, 2002; Nebes et al., 2000; Rapp et al., 2005; Sheline et al., 2006). Of these domains, information processing speed and executive functioning appear particularly vulnerable, and several studies have reported that cognitive impairment associated with LLD appears to be predominantly mediated by slowed information processing and/or working memory deficits. Nebes and colleagues (2000) found that depressed older adults performed significantly worse on measures of both processing speed and working memory, and while performance on these measures improved in patients whose LLD remitted, the extent of
    improvement was no greater than that seen in comparison subjects who underwent repeat assessment. In a similar vein, Butters and colleagues (2004) reported that relative to non depressed comparison subjects, LLD patients performed poorer in all cognitive domains, with information processing
    speed and visuospatial and executive abilities being the most broadly and frequently impaired. More recently, Sheline and colleagues (2006) found that age, depression severity, education, race, and vascular risk factors all made significant and independent contributions to cognitive impairment in LLD, and that changes in information processing speed mediated the influence of predictor variables on other cognitive domains. In addition, patients with LLD who exhibit executive dysfunction may be at higher risk for poor outcomes, as deficits in executive functioning have been associated with poor or delayed antidepressant treatment response (Alexopoulos et al., 2005) as well as higher relapse and recurrence rates in some studies (Alexopoulos et al., 2000),
    although not in others (Butters et al., 2004).
  • Algunos cambios en el humor:
    Incremento: desinhibición, impulsividad, pobre autorregulación, conducta social inapropiada.
    Disminución: afecto, iniciativa, falta de interés en actividades sociales
  • Los SPCD aparecen en todos los estadios de la EA, algunas veces, 2 años antes del diagnostico. El pico de frecuencia de los trastornos se muestran en el momento de aparición en la evolución de la enfermedad. Por ejemplo, el aislamiento social ocurre 33 meses antes del diagnostico y constituye el síntoma psicológico reconocible mas temprano. Ideación suicida, depresión, paranoia y trastornos del ritmo del sueño aparecen también tempranamente en el curso de la enfermedad; mientras que agitación, alucinaciones y agresividad suelen aparecer en promedio 1-2 años después del diagnostico.
  • MAASBED: Maastricht Study of behavior in dementia,
    REAL-FR: Reseaux Alzheimer Francais,
    EADC: European Alzheimer Disease consortium.
    Robert, P. H. et al. (2005). Grouping for behavioral and psychological symptoms in dementia: clinical and biological aspects. Consensus paper of the European Alzheimer Disease Consortium. European Psychiatry, 20, 490–496.
  • It shows the evolution of behavioral changes, in terms of Neuropsychiatric Inventory (NPI) symptoms, as found in the Cache County Study (five-year period prevalence; Steinberg, M. et al.; Cache County Investigators. (2008). Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. International Journal of Geriatric Psychiatry, 23, 170–177.). Latent class and factor analytic studies suggest the existence of several overlapping behavioral syndromes or factors (Frisoni et al., 1999; Lyketsos et al., 2001; Moran et al., 2004). Frisoni et al. (1999) grouped these into three syndromes: “psychotic” (agitation, hallucinations, delusions, irritability), “mood” (anxiety, depression), and “frontal” (disinhibition, euphoria). Lyketsos et al. (2001) identified three groupings: “no neuropsychiatric symptoms”, “affective” and “psychotic” symptoms.
    The most frequently occurring of the NPS are apathy, depression, and anxiety (Robert et al., 2005; Steinberg et al., 2008)
  • The MRC CFAS has been fully described elsewhere. It is a multicentre longitudinal population-based study of ageing, with a focus on cognitive and physical decline. Random samples of people aged 65 years and over were contacted at each of five centres representative of rural and urban areas in England and
    Wales (Cambridgeshire, Gwynedd, Newcastle upon Tyne, Nottingham and Oxford) with an 82% response rate. A total of 13, 004 participants were followed.
  • The prevalence of each symptom is significantly higher in the population with dementia except for sleep problems, which are very common in both groups, and anxiety, which was around 40% more common in the population with dementia (P=0.07). A more detailed analysis of responses relating to sleep problems revealed that people with dementia self-report fewer sleeping problems, although their carers report significantly more. Apathy is the most prevalent non-cognitive symptom of dementia, present in 50.3% of those with dementia compared with 12.1% of the population without dementia.
  • La apatía y los síntomas depresivos (estos últimos no siempre conformando un síndrome depresivo mayor completo) constituyen dos entidades de presentación muy frecuente en cualquier tipo de demencia. La ausencia de motivación e interés por el entorno, y por nuevos estímulos, constituye el núcleo sintomático principal de la apatía y suele estar presente también, en mayor o menor medida, en los síndromes depresivos. El solapamiento del síndrome
    amotivacional común a la apatía y a la depresión en los enfermos con demencia, dificulta habitualmente la labor de diagnóstico diferencial de esta condición por parte del clínico.
    Existen dos momentos en el curso evolutivo de un síndrome de demencia en los que resulta particularmente útil la correcta diferenciación de apatía y depresión. El primero está relacionado con las fases iniciales de los procesos de deterioro cognitivo en las que son especialmente frecuentes los cambios en la personalidad del paciente como único síntoma. En este caso, una progresiva actitud de desconexión del ambiente, aparentemente sin justificación
    alguna, desconocida para el comportamiento habitual previo del sujeto, debería poner sobre aviso para la detección precoz de un proceso que puede producir demencia. El otro momento de interés para la correcta diferenciación de ambas condiciones tiene que ver con el abordaje elegido para tratarlas. Aunque en el manejo terapéutico de los diferentes síntomas psicológicos y conductuales de la demencia existen frecuentes estrategias comunes,
    la apatía y la depresión pueden responder de forma diferenciada a pautas farmacológicas y no farmacológicas distintas. Desde el punto de vista clínico, en los casos en los que la apatía está presente de forma importante, ésta tiende a limitar o matizar la contundencia de otros síntomas más disruptivos
    que hayan podido darse previamente. En este sentido, podría decirse que la apatía contribuiría a mejorar la expresión de otros síntomas psiquiátricos o conductuales en los síndromes de demencias. Esta evolución puede apreciarse, principalmente, en algunos casos de demencia frontotemporal a lo largo
    de su progresión en el tiempo, con un predominio inicial de conductas de carácter más psicopático que acaba en actitudes predominantemente
    apáticas.

    Apathy is defined as diminished activity due to lack of motivation (Starkstein, Ingram, Garau, & Mizrahi, 2005a). Among patients with AD, apathy is manifested as diminished drive to perform their daily chores, low interest about family activities, and emotional indifference to positive or negative
    events. AD patients with apathy put little effort into their usual chores and need help from a caregiver to structure their routines. Depression is frequently
    associated with apathy in AD, an expected finding given that loss of interest and motivation is a cardinal symptom of both apathy and depression. For
    instance, key symptoms of apathy such as loss of interest and psychomotor retardation are specific DSM-IV diagnostic criteria for depression, and about two thirds of AD patients with apathy also have depression. In a recent study Starkstein and co-workers examined the association between apathy and depression in the context of a longitudinal study that included 247 patients with AD (Starkstein, Jorge, Mizrahi, & Robinson, 2006). In a cross sectional
    analysis about one quarter of patients without depression had apathy, demonstrating that depression is not necessary for apathy in AD. On the other hand, about half of the patients with depression had apathy, demonstrating that depression is not sufficient for apathy in AD. After a mean follow-up
    period of 18 months there was a significant increase on apathy scores over time, but syndromal depression at baseline (i.e. major or minor depression) was
    not significantly associated with more severe apathy at follow-up. On the other hand, the presence of apathy at baseline was a significant predictor of
    increasing depression during follow-up, suggesting that apathy may be an early marker or a prodromal stage of depression in AD.
  • One of the main limitations to a valid diagnosis of depression in dementia is the overlap between symptoms of depression and symptoms of cognitive and functional decline. For instance, insomnia, psychomotor retardation, loss of energy, loss of libido, and poor appetite are common among patients with dementia, but are also clinical criteria for a DSM-IV diagnosis of major depression. Several studies examined the specificity of symptoms of depression in AD. Chemerinski and co-workers (2001) assessed a series of 233 patients with AD, 47 patients with depression without dementia, and 20 age-comparable healthy individuals for the frequency of depressive symptoms. The main finding was that the presence of sad mood was associated with significantly higher scores on the HAM-D items rating guilt, suicide, insomnia, loss of interest, retardation, agitation, worry, anxiety, loss of energy, loss of libido, and hypochondriasis, but not loss of appetite. This finding demonstrates that both physical and psychological symptoms of depression are frequent among AD patients with sad mood. Another important finding of this study was that AD patients without sad mood had no more symptoms of depression than did age-comparable healthy individuals, demonstrating that physical and psychological symptoms of depression should not be necessarily construed as mere epiphenomena of a chronic neurological disease, but may be specific to depression in AD. Furthermore, only 2% of the AD patients met the DSM-IV criteria for major depression without having sad mood or loss of interest, confirming that symptoms of depression are uncommon among AD patients without
    sad mood. Lyketsos and co-workers (2001) suggested an empirically based taxonomy of psychiatric disorders in AD. They suggested that the ‘individual symptom approach’ may ignore the high comorbidity of psychiatric symptoms and syndromes in AD and should not be used. The authors examine a large
    series of AD patients living in the community, and using latent class analysis they identified a group (27% of the participants) who exhibited affective symptoms of depression, anxiety, irritability and apathy. Based on these findings, they proposed specific diagnostic criteria for AD-associated
    affective disorder.
  • En el diagnóstico diferencial entre los cuadros afectivos del anciano y la demencia, resulta ya clásica la consideración de la pseudodemencia depresiva o, más propiamente, el síndrome de demencia de la depresión, que se define, esencialmente, como un deterioro intelectual en un paciente con trastorno psiquiátrico primario. Los síntomas se asemejan, al menos en parte, a los de la demencia orgánica, la afectación intelectual es reversible y se da en ausencia
    de un proceso neuropatológico primario causante del deterioro cognitivo. Aunque la depresión es su causa más frecuente, puede darse en numerosos cuadros psiquiátricos. Se estima que entre un 18-57% de ancianos deprimidos tienen un síndrome de demencia y que alrededor de 8-15% de demencias
    diagnosticadas son en realidad depresiones. En seguimientos a 8 años hasta un 89% acaban evolucionando hacia una demencia. La presencia de pseudodemencia implica depresión con peor pronóstico. De igual forma, en los cuadros maníacos, especialmente en los pacientes de más edad, puede darse la denominada pseudodemencia maníaca, que suele asociarse con frecuencia a un infradiagnóstico del trastorno afectivo de base al quedar sumergido en la impresión clínica del síndrome de demencia sin que éste haya sido confirmado mediante un adecuado proceso de evaluación diagnóstica. Recientes investigaciones han demostrado que, al igual que sucede con la depresión unipolar, especialmente en pacientes ancianos con afectación cognoscitiva, también en el trastorno bipolar de inicio tardío ha podido documentarse una reducción del volumen del núcleo caudado, mayor que en sujetos controles, mediante RMN sin que parezca guardar relación con el tiempo de duración o la edad de inicio de la enfermedad. Asimismo, se evidencia una mayor reducción del volumen cerebral total de los pacientes con inicio tardío de la enfermedad bipolar en relación con los que la iniciaron más precozmente.
    El trastorno bipolar y la demencia se han estudiado como entidades clínicas diferentes. En contraste con la depresión unipolar, los trastornos del espectro bipolar no han sido tenidos en cuenta con la misma frecuencia en el diagnóstico diferencial de la demencia. Recientes estudios proponen una aproximación entre los cuadros de inestabilidad del estado de ánimo de inicio en la edad tardía y la demencia a través de aspectos clínicos y neurobiológicos
    comunes entre ambas entidades, como el propuesto trastorno bipolar tipo VI o diátesis bipolar de la demencia. Aunque hasta ahora se atribuía a la demencia una baja tasa de suicidio, se sabe actualmente que las fases incipientes de una demencia pueden exponer a un mayor riesgo de conductas autolíticas. Estudios epidemiológicos recientes sugieren que la disfunción cognitiva leve o la demencia leve son frecuentes en los intentos suicidas, que la asociación de dos entidades frecuentes en la edad avanzada (depresión y disfunción cognitiva) incrementa el riesgo de suicidio y, finalmente, que la afectación de la capacidad cognitiva reduce la posibilidad de afrontar conflictos y aumenta las denominadas respuestas catastróficas en las que el paciente, atrapado en un conflicto que no comprende, o ante el que no es capaz de ver una salida, responde con una conducta autolesiva de carácter impulsivo en la mayor parte de ocasiones y, más raramente, con algún grado de premeditación o planificación. Esta condición parece especialmente relevante en situaciones de comunicación al paciente del diagnóstico de demencia.
  • En el diagnóstico y, sobre todo, en el seguimiento evolutivo de los pacientes ancianos deprimidos pueden resultar de ayuda las escalas de valoración de síntomas depresivos validadas para pacientes de más de 65 años. En nuestro medio, la más utilizada es la escala de depresión geriátrica de Yesavage (GDS) de 30 ítems, con versiones breves de 15 ítems. Existen, incluso, versiones muy reducidas (5 ó 4 ítems), útiles para el screening o despistaje sistemático de síntomas depresivos en ancianos. En entornos asistenciales con escasez de tiempo para la exploración psicopatológica detenida, pueden resultar útiles estrategias de cribado sistemático que puedan identificar sujetos ancianos en riesgo de sufrir depresión y que merecerían un examen más detallado.
    Cuando el nivel cognoscitivo está comprometido, la validez de estas escalas está muy reducida, por lo que resulta preferible utilizar instrumentos validados en estas condiciones. Algunas de ellas se han desarrollado con el objetivo específico de la identificación de síntomas depresivos en la demencia, como la Dementia Mood Assessment Scale o, de uso más común en los últimos años, la subescala de depresión/disforia del inventario neuropsiquiátrico (NPI) de Cummings. Esta última, tras una pregunta de selección seguida de ocho preguntas de confirmación, establece una identificación clínica del síndrome,
    aunque con tendencia al sobrediagnóstico si se utiliza en estudios clínicos o epidemiológicos. Se han publicado validaciones para el uso en pacientes con demencia de la escala de Yesavage de 30 y de 15 ítems y, recientemente, en castellano las versiones de 15 y 5 ítems. La más utilizada y validada en castellano es la escala de Cornell para valoración de síntomas depresivos en la demencia y suele recomendarse su aplicación cuando la puntuación del Mini Mental Estate Examination (MMSE) sea igual o inferior a 18 puntos. Dada la dificultad en la valoración clínica de los síntomas depresivos en los pacientes con demencia, la familiarización con este tipo de instrumentos puede resultar de ayuda para el diagnóstico de la depresión y en su seguimiento terapéutico.
  • The NIMH workgroup proposed standardized diagnostic criteria for depression in AD (Olin et al., 2002a, 2002b) . These are similar to the DSM-IV criteria for major depression, but with the inclusion of irritability and social isolation replacing loss of libido, and with loss of pleasure in response to social contact replacing loss of interest. The NIMH criteria require three symptoms for the diagnosis of depression instead of the five required by the DSM-IV criteria for a major depressive episode, and symptoms are not required to be present nearly every day.
  • Few studies have examined the validity of the NIMH criteria. Starkstein and co-workers found that 41% of depressed AD patients in the stage of severe dementia had no sad mood (i.e. depression was diagnosed based on the presence of loss of interest/anhedonia) suggesting that the NIMH
    criteria may have low specificity for depression in the late stages of dementia. A recent study by Vilalta- Franch et al. (2006) compared the frequencies of
    depression resulting from using 4 different diagnostic schemes for depression in a sample of 491 patients with AD. Frequencies of major or severe depression were 5% for the International Classification of Diseases, 10th Revision (ICD-10) criteria, 10% for the Cambridge Examination for Mental Disorder of the Elderly (CAMDEX) diagnostic criteria, 13% for the DSM-IV criteria for major depression, and 27% for the NIMH work group criteria. The authors
    stressed that the requirements of loss of confidence/ self-esteem and irritability accounted for a large variance of the discrepancies. In a recent study Starkstein and co-workers (2005c) examined the temporal stability of symptoms of depression in a series of 65 AD patients with depression at baseline that were re-assessed for depression an average of 17 months later. At follow-up about half of the sample had no depression and showed a significant improvement in the symptoms of sadness, guilt, suicidal ideation, disruption in sleep, loss of interest, loss of energy, thoughts of death, social withdrawal, psychomotor changes, changes in appetite/weight, and symptoms of anxiety. On the other hand, no significant between-group changes were found on scores of irritability or apathy. The finding that symptoms of anxiety co-varied over time with the presence of depression suggests that anxiety is attributable
    to depression rather than to dementia. On the other hand, the lack of changes on scores of irritability among patients with remission of depression suggests
    that irritability should not be construed as a criterion for depression in AD. One limitation to assess mood changes in dementia is that patients with AD may under-report depressive symptoms due to poor awareness of their behavioural and emotional changes.
    Chemerinski and colleagues (2001) examined discrepancies between patients’ and caregivers’ reports of depressive symptoms, and found that AD patients
    under-rated the severity of their depressive symptoms as compared to reports provided by their respective caregivers. Another confounder is that
    depression in caregivers may influence depression ratings of patients. However, while some studies found a significant influence of caregivers’ depression
    on patients’ own ratings of depression (Teri & Truax, 1994) other studies showed no significant impact (Loewenstein et al., 2001). In a recent 12-week study on the efficacy of sertraline among AD patients with depression, Rosenberg and coworkers (2005) found that both caregiver depression and burden decreased during the three months of the study, although these changes were not associated with improvement in patient mood as rated by the caregivers.
    Taken together, these findings suggest that both physical and psychological symptoms of depression are frequent in AD. However, in the absence of
    sad mood, symptoms of depression are no more prevalent in AD than in age-comparable individuals without dementia, suggesting that physical and
    psychological symptoms of depression are not epiphenomena of a chronic neurological disease, but constitute specific symptoms of a mood disorder.
  • La evaluación de depresión en un paciente con EA es un reto. El compromiso del lenguaje y la memoria en EA puede hacer difícil al paciente para comprender o recordar las preguntas, o reportar exactamente sus síntomas. Esta puede ser una razón por la que algunos estudios han encontrado altas tasas de depresión cuando los cuidadores mas que los pacientes han sido interrogados acerca de los síntomas. Por ejemplo en su estudio de depresión en pacientes con EA, Chemerinski y colaboradores encontraron que los cuidadores reportan puntuaciones mas elevadas que las reportadas por los mismos pacientes, sugiriendo que los pacientes pueden no tener real conciencia de la severidad de sus síntomas depresivos. No obstante, los mismos cuidadores que están también deprimidos pueden ser mas susceptibles de atribuir síntomas depresivos de los pacientes con EA (Chemerinski, 2002, Lyketsos, 2004).

    Depression rating scales are useful to rate the severity of depressive disorders and may also be used as screening instruments to determine the likelihood
    of the presence or absence of mood disorders in dementia. The Hamilton Depression Rating Scale (HAM-D) is a 17-item interviewer-rated scale that
    measures psychological and autonomic symptoms of depression (Hamilton, 1960). This instrument assesses the individual’s mood, self-esteem, suicidal
    ideation and interest in daily life activity and work productivity. Other HAM-D items, such as those rating sleep problems, psychomotor retardation,
    poor concentration, loss of energy, and hypochondriasis may be difficult to assess in patients with AD. The Geriatric Depression Scale (GDS) is a short
    screening instrument for depression in the elderly that focuses on psychosocial aspects of depression, avoiding symptoms that may overlap with medical
    disorders or aging (Yesavage et al., 1982). One limitation of the GDS is that it is a self-report instrument, and some of the questions may be difficult for patients with moderate or severe dementia to answer reliably. The Cornell Scale for Depression in Dementia (CSDD) was developed to specifically assess depressive symptoms in dementia and is based on information provided by a caregiver and the patient (Alexopoulos, Abrams, Young, & Shamoian, 1988). If the examiner considers that some of the symptoms are secondary to the cognitive deficits, those symptoms should not be considered for the final score.
  • La escala de depresión de Cornell sirve para detectar signos depresivos en lugar de los síntomas (conducta depresiva) observados durante la última semana:
    • Consta de 19 ítems con tres grados de intensidad (ausente, leve/inconstante, severo)
    • Entrevista en dos etapas: cuidador y paciente
    • Reentrevista al cuidador si hay discrepancias
    • Puntuación según juicio clínico (no punto de corte)

    Fármacos que pueden producir depresión:
    Betabloqueantes pueden causar depresión, los tres efectos adversos que se manifiestan más comúnmente como consecuencia de su uso son la fatiga, la disfunción sexual y la depresión.
    Anticonvulsivos
    Benzodiazepinas
    Uso crónico de corticoides
    Metilfenidato y Modafinilo
    Estatinas
    Inhibidores de la bomba de protones
    Anticolinérgicos de uso intestinal
  • Randomized controlled trials using selective serotonergic re-uptake inhibitors (SSRIs) demonstrated a significant efficacy over placebo for citalopram and
    sertraline, but not for fluoxetine (Lyketsos & Lee, 2004) (Petracca, Chemerinski, & Starkstein, 2001). Whereas SSRIs are better tolerated than tricyclics,
    they may induce agitation, anxiety, tremor and sleep problems. Autonomic changes such as dry mouth, sweating, loss of weight and diarrhoea may
    also occur. Concurrent administration of opiates or monoamine oxidase inhibitors increases the risk of serotonin syndrome and the concomitant use of
    these medications should be avoided. Tricyclics are rarely used to treat depression in AD given their relatively frequent side-effects among elderly individuals, important contra-indications and high lethality index. A randomized controlled trial using the tricyclic clomipramine demonstrated a
    greater efficacy of the active compound over placebo (Petracca, Teson, Chemerinski, Leiguarda, & Starkstein, 1996). On the other hand, other studies found no significant differences between the tricyclics maprotiline or imipramine over placebo (Lyketsos & Lee, 2004). Side-effects are frequently reported in elderly individuals on tricyclics. The most dangerous adverse event is a delay in cardiac conduction and a potential heart block. Orthostatic hypotension is a frequent problem with tricyclics, and other anticholinergic side-effects include dry mouth, reduced tear flow, impaired visual accommodation,
    constipation, urinary retention and cognitive changes characterized by confusion or overt delirium. Sedation and weight gain are other frequent problems. Contraindications to the use of tricyclics are myocardial infarction within the past 6 months, first- or second-degree heart block or life threatening arrhythmias, history of prostatic hypertrophy, difficult to treat seizures and glaucoma. A randomized controlled trial using the reversible monoamine oxidase inhibitor (MAOI) moclobemide demonstrated a significant efficacy of this medication over placebo (Roth, Mountjoy, & Amrein, 1996). Side effects for moclobemide were mild and mostly included restlessness, dizziness, nausea and constipation.
  • Background: Antipsychotics are frequently used to treat psychosis, aggression and agitation in patients with Alzheimer’s disease (AD), but safety warnings abound. Escitalopram was investigated since citalopram has demonstrated some effectiveness in AD. We compared escitalopram and risperidone for psychotic symptoms and agitation associated with AD. Methods: Inpatients with AD, who had been hospitalized because of behavioral symptoms, were recruited to a six-week randomized, double-blind, controlled trial. Participants (n = 40) were randomized to once daily risperidone 1 mg or escitalopram 10 mg. Results: The NPI total score improved in both groups. Onset was earlier in the risperidone-treated group, but improvement did not significantly differ between groups by study end. Completion rates differed for escitalopram (75%) and risperidone (55%), mainly due to adverse events. There were no adverse events in the escitalopram group, while in the risperidone group two patients suffered severe extrapyramidal symptoms and four patients suffered acute physical illness necessitating transfer to general hospital. Conclusion: Escitalopram and risperidone did not differ in efficacy in reducing psychotic symptoms and agitation in patients with AD. Completion rates were higher for escitalopram-treated patients. Replication in larger trials with ambulatory patients is needed.
  • IMPORTANCE Agitation is common, persistent, and associated with adverse consequences for patients with Alzheimer disease. Pharmacological treatment options, including antipsychotics are not satisfactory. OBJECTIVE The primary objective was to evaluate the efficacy of citalopram for agitation in patients with Alzheimer disease. Key secondary objectives examined effects of citalopram on function, caregiver distress, safety, cognitive safety, and tolerability.
    DESIGN, SETTING, AND PARTICIPANTS The Citalopram for Agitation in Alzheimer Disease Study (CitAD) was a randomized, placebo-controlled, double-blind, parallel group trial that enrolled 186 patients with probable Alzheimer disease and clinically significant agitation from 8 academic centers in the United States and Canada from August 2009 to January 2013. INTERVENTIONS Participants (n = 186) were randomized to receive a psychosocial intervention plus either citalopram(n = 94) or placebo (n = 92) for 9weeks. Dosage began at 10mgper day with planned titration to 30mgper day over 3weeks based on response and tolerability. MAIN OUTCOMES AND MEASURES Primary outcome measures were based on scores from the 18-point Neurobehavioral Rating Scale agitation subscale (NBRS-A) and the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC). Other outcomes were based on scores from the Cohen-Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory (NPI), ability to complete activities of daily living (ADLs), caregiver distress, cognitive safety (based on scores from the 30-point Mini Mental State Examination [MMSE]), and adverse events.
    RESULTS Participants who received citalopram showed significant improvement compared with those who received placebo on both primary outcome measures. The NBRS-A estimated treatment difference at week 9 (citalopram minus placebo) was −0.93 (95%CI, −1.80 to −0.06), P = .04. Results from the mADCS-CGIC showed 40% of citalopram participants having moderate or marked improvement from baseline compared with 26%of placebo recipients, with estimated treatment effect (odds ratio [OR] of being at or better than a given CGIC category) of 2.13 (95%CI, 1.23-3.69), P = .01. Participants who received citalopram showed significant improvement on the CMAI, total NPI, and caregiver distress scores but not on the NPI agitation subscale, ADLs, or in less use of rescue lorazepam. Worsening of cognition (−1.05 points; 95%CI, −1.97 to −0.13; P = .03) and QT interval prolongation (18.1 ms; 95%CI, 6.1-30.1; P = .01) were seen in the citalopram group. CONCLUSIONS AND RELEVANCE Among patients with probable Alzheimer disease and agitation who were receiving psychosocial intervention, the addition of citalopram compared with placebo significantly reduced agitation and caregiver distress; however, cognitive and cardiac adverse effects of citalopram may limit its practical application at the dosage of 30mgper day.
  • Manejo de Depresión en Demencia y Enfermedad de Alzheimer

    1. 1. MANEJO DE DEPRESIÓN EN DEMENCIA Y ENFERMEDAD DE ALZHEIMER TALLER DE ACTUALIZACIÓN EN MANEJO DE ENFERMEDADES NEURODEGENERATIVAS 24 Mayo 2014, Paracas-Perú Nilton Custodio Instituto Peruano de Neurociencias ncustodio@ipn.pe
    2. 2. • Expositor contratado: – Laboratorio Novartis-Perú. – Janssen-Cilag-Región Sudamérica. – Laboratorio Farmindustria-Perú. – Boehringer-Ingelheim-Región Sudamérica. – Laboratorio Lilly-Perú. – Laboratorios Tecnofarma-Perú. – Laboratorios Roemmers-Perú. • Investigador contratado: – Laboratorio Novartis-Suiza – Laboratorio Pfizer-USA – Merck-Sharp-Dohme-USA – Medivation-USA • Investigador independiente: – Unidad de Investigación – Clínica Internacional. – Unidad de diagnostico de deterioro cognitivo y prevención de demencia – IPN Declaración de conflictos de intereses
    3. 3. Agenda • Depresión como factor de riesgo de demencia. • Depresión como síntoma inicial de demencia. • Los síntomas cognitivos de la depresión. • Depresión en demencia diagnosticada previamente. • Evaluación clínica del paciente con depresión y demencia. • Manejo del paciente con depresión y demencia.
    4. 4. Agenda • Depresión como factor de riesgo de demencia. • Depresión como síntoma inicial de demencia. • Los síntomas cognitivos de la depresión. • Depresión en demencia diagnosticada previamente. • Evaluación clínica del paciente con depresión y demencia. • Manejo del paciente con depresión y demencia.
    5. 5. Factor edad e inicio de síntomas depresivos • Depresión de la tercera edad-DTE (≥ 60 años): Incluye a depresión de inicio tardío (DIT) e involucra además a los individuos con síntomas recurrentes desde la edad adulta (DIP). • Prevalencia DTE: 1-4 % en comunidad, 10-12% en hospitalizados. • DTE caracterizada por menor probabilidad de tristeza; muestran más agitación o síntomas somáticos: insomnio, fatiga. • Prevalencia real DTE: 8-16 % en comunidad, 30% en hospitalizados.
    6. 6. Evaluación de cohortes de pacientes con depresión como factor de riesgo de demencia S E V E R I D A D Riesgo para 1 episodio depresivo Riesgo para ≥ 2 episodios depresivos Riesgo para historia de depresión y depresión en evaluación basal Duración de depresión no es factor de riesgo Da Silva J et al. BJP 2013:202:177-186
    7. 7. DTE es factor de riesgo más significativo para demencia vascular comparado con EA Diniz BS et al. BJP 2013:202:329-335
    8. 8. Potenciales vías relacionadas entre DTE y el inicio de los síntomas de demencia Depresión Disfunción eje H H A glucocorticoides Inflamación crónica: Enfermedad cerebrovascular Atrofia hipocampal Isquemia Frontoestriatal Reserva Cerebral PATOLOGÍA EA CLÍNICA EA OTROS FACTORES EA Koenig AM et al. JINS 2014:20:1-7
    9. 9. Agenda • Depresión como factor de riesgo de demencia. • Depresión como síntoma inicial de demencia. • Los síntomas cognitivos de la depresión. • Depresión en demencia diagnosticada previamente. • Evaluación clínica del paciente con depresión y demencia. • Manejo del paciente con depresión y demencia.
    10. 10. Depresión en los estadios iniciales de demencia, Deterioro Cognitivo Leve (DCL) • Depresión en individuos con DCL: 26%1. • DCL amnésico en deprimidos vs no deprimidos: 50%2 vs 3-6%1. • En estudios de seguimiento no hay incremento de síntomas depresivos durante fases pre-clínicas de EA4. • DCL persiste, aún después que los sintomas depresivos han remitido3. • Compromiso persistente de memoria en el contexto de depresión puede ser un indicador de cambios estructurales4. 1. Lopez OL. Arch Neurol 2003;60:1385-1389 2. Adler AG. Eur Psychiatry 2004;19:502-505 3. Reischies FM. Eur Arch Psychiatry Clin Neurosci 2000;50:186-193 4. Wilson RS. Neurology 2010;75:21-26 5. Butters MA. Am J Psychiatry 2000;157:1949-1954 Es una reacción al estrés emocional? Esta asociación no es debida a estrés emocional
    11. 11. Depresión incrementa la posibilidad de conversión de DCL a demencia de EA DCL DEMENCIADEPRESIÓN DCL DEMENCIA DEPRESIÓN DCL DEMENCIA DTE BIOMARCADORES
    12. 12. Resultados en evaluación de riesgo de demencia asociados a depresión de inicio precoz (DIP) y tardío (DIT) Da Silva J et al. BJP 2013:202:177-186 El compromiso cognitivo es significativamente mayor en DIT comparado con DIP Sugiere una plataforma neuropatológica común basado en disfunción vascular
    13. 13. DTE está asociada a cambios en sustancia blanca y pobre respuesta a tratamiento según IRM Alexopoulos GS et al. Am J Psychiatry 2008;165(2):238-244
    14. 14. Cambios similares se observan en individuos con demencia por EA Hirono N et al. Stroke 2000;31(9):2182-2188
    15. 15. La disrrupción de los circuitos fronto-estriatales por LSB perpetúan los síntomas depresivos? O’Brien JT et al. Am J Geriatr Psychiatry 2006;14:834-841
    16. 16. Asociación entre depresión con LSB frontal y LSB temporal; pero no con infartos lacunares Característica Valor p Wald x2 (df=1) Odds ratio (95% CI) Edad 0.4 0.8 0.99 (0.96-1.02) Stroke 0.4 0.7 0.87 (0.62-1.22) Calidad de vida <0.001 159.0 0.94 (0.93-0.95) MMSE <0.001 29.0 0.85 (0.8-0.9) HTA 0.5 0.4 0.81 (0.41-1.59) LSB frontal 0.4 0.8 1.1 (0.89-1.36) LSB temporal 0.024 5.1 1.3 (1.03-1.65) Lagunas GB 0.2 1.5 0.87 (0.68-1.1) LSB frontal-HTA 0.9 0.02 1.02 (0.79-1.31) LSB temporal-HTA 0.038 4.3 0.75 (0.57-0.99) Lagunas GB-HTA 0.2 1.5 1.18 (0.91-1.53) O’Brien JT et al. Am J Geriatr Psychiatry 2006;14:834-841
    17. 17. Estudio longitudinal de cambios de LSB en pacientes con DTE están asociados con demencia Steffens DC et al. Am J Geriatr Psychiatry 2007;15(10):839-849
    18. 18. DepresiónvsDemenciaDepresiónvsControles Herrera-Pérez E et al. Dement Geriatr Cogn Disord Extra 2013;3:333-341 En la práctica clínica el ACE puede discriminar entre depresión y demencia en estadios iniciales
    19. 19. Agenda • Depresión como factor de riesgo de demencia. • Depresión como síntoma inicial de demencia. • Los síntomas cognitivos de la depresión. • Depresión en demencia diagnosticada previamente. • Evaluación clínica del paciente con depresión y demencia. • Manejo del paciente con depresión y demencia.
    20. 20. Demencia inicial o síntomas cognitivos de depresión: Reto del diagnóstico clínico • Individuos con depresión en el contexto de demencia inicial. – perdida de memoria, agitación, disturbio del ciclo sueno- vigilia y apatía. • Individuos con quejas cognitivas como parte de su episodio depresivo. – concentración disminuida, disminución de la velocidad del procesamiento de la información, irritabilidad, perdida del sueño, fatiga y anhedonia.
    21. 21. Claras diferencias en estados establecidos de episodio depresivo mayor y enfermedad de Alzheimer Característica EDM EA Diagnóstico Criterios EDM Algunos criterios EDM Edad de inicio Antes o después de 60 Raro antes de los 60 Forma de inicio Típicamente agudo Insidioso Curso Fluctuante Declinación progresiva Quejas de memoria Usualmente presente Variable Afecto Deprimido Deprimido o eutímico Ciclo sueño-vigilia Usualmente alterado Variable Afasia/apraxia/agnosia Raramente alterado Conforme progresa Memoria Mejora con “claves” No mejora con “claves” Disfunción ejecutiva Típico Tardíamente Velocidad procesamiento Enlentecido Normal Potter GG, Steffens DC. The Neurologist 2007;13:105-117
    22. 22. Características distintivas de la historia clínica en depresión vs demencia • Edad de inicio: – EA infrecuente antes de los 60 años de edad. • Tasa de cambio: – En EA el inicio es insidioso y progresión gradual en años. • Queja de los síntomas: – En EA “la familia o los cuidadores se quejan” – En depresión “el paciente se queja”
    23. 23. Función cognitiva en DTE: Alteración en memoria episódica y de trabajo • Olvidos frecuentes de citas, recados, actividades domésticas. • Repetición de los temas de conversación. • Repetir la misma pregunta una y otra vez. • Desorientación en áreas familiares fuera de su domicilio. • Dificultad para aprender nueva información: – Rutas alternativas al supermercado, a casa de los hijos, al banco o al CAM. – Nuevas tareas domésticas, laborales y sociales. – Uso de nuevas aplicaciones en modernos electrodomésticos. – Rechazo a los artículos electrónicos y redes sociales.
    24. 24. Función cognitiva en DTE: Alteración en funciones ejecutivas y viso-espaciales Funciones Ejecutivas Funciones Viso-espaciales • Desorganización. • Pobre planificación. • Pésimo en las multi-tareas. • Perseveración. • Disminución en capacidad de abstracción. • Dificultad para precisar los desplazamientos (incluso dentro de casa). • Problemas para completar tareas que involucran uso de botones o manijas. • Dificultad para vestirse. • Problemas para encontrar objetos delante de su “panorama”. • Mala percepción de la información visual.
    25. 25. Función cognitiva en DTE: Alteración en atención y lenguaje Atención Lenguaje • Inicia tareas, pero no las termina. • “Sensación de ausencia”. • Dificultad para seguir la conversación. • Distraído. • Lentitud en la velocidad del proceso de pensamiento. • Dificultades para expresar lo que piensa (no encuentra palabras idóneas). • Con frecuencia, uso inadecuado de las palabras. • Problemas para escritura: ortografía. • Dificultad para comprender la conversación.
    26. 26. Perfil neurocognitivo de DTE LEVE NORMAL SEVERO Atención Humor Lenguaje Espacial Memoria AVDs Ejecutiva MODERADO Inicial: (2 a después de inicio)
    27. 27. Perfil neurocognitivo de DCL LEVE NORMAL SEVERO Atención Humor Lenguaje Espacial Memoria AVDs Ejecutiva MODERADO Inicial: (2 a después de inicio)
    28. 28. En la práctica clínica diaria, el “seguimiento” de un caso de “queja de memoria” es clave Evaluación basal • F, 68, diestra. • Magister en educación. • Antecedentes de enfermedad cardiovascular: HTA • Acude por quejas de memoria: • Insidiosa • progresiva • Declinación de memoria desde hace 2 años. • Mantiene habilidades sociales. • Vive sola, y es independiente para AVD instrumentales. • Sus familiares han notado los cambios.
    29. 29. • Sensación de progresión de quejas de memoria. • Aún mantiene habilidades sociales. • Hasta ahora, vive sola y es independiente para AVD básicas. • Algunos cambios en AVD instrumentales: – Problemas para conducir su vehículo (accidentes menores, y problemas en la orientación espacial) – Problemas para manejar sus medicamentos. En la práctica clínica diaria, el “seguimiento” de un caso de “queja de memoria” es clave Cambios en la segunda visita
    30. 30. LEVE NORMAL SEVERO Atención Humor Lenguaje Espacial Memoria AVDs Ejecutiva MODERADO Inicial: (2 a después de inicio) 1a Seg: (3 a despúes de inicio) 2 a Seg: (5 a después de inicio) Perfil neurocognitivo longitudinal de DCL
    31. 31. Perfil neurocognitivo longitudinal de demencia LEVE NORMAL SEVERO MODERADO Atención Humor Lenguaje Espacial Memoria AVDs Ejecutiva Inicial: (2 a después de inicio) 1a Seg: (3 a despúes de inicio) 2 a Seg: (5 a después de inicio)
    32. 32. En la práctica clínica diaria, el “seguimiento” de un caso de “queja de memoria” es clave Evaluación basal • M, 65, diestro, viudo. • Coronel de Sanidad EP. • Antecedentes de enfermedad cardiovascular: Dislipidemia, HTA. • Acude por quejas de memoria: • Insidiosa • progresiva • Declinación de memoria desde hace 2 años. • Pérdida de interés en el tenis y habilidades sociales. • Vive solo, y es independiente para AVD básicas. • Fallas en AVD instrumentales: Olvida dosis de medicación, inatención al manejar • Sus hijos han notado los cambios.
    33. 33. Perfil neurocognitivo longitudinal de depresión LEVE NORMAL SEVERO MODERADO Inicial: (2 años después de inicio) Tto x 1 a: (Remisión incomplete) Tto x 1 a: (Efectivo) Atención Humor Lenguaje Espacial Memoria AVDs Ejecutiva
    34. 34. Agenda • Depresión como factor de riesgo de demencia. • Depresión como síntoma inicial de demencia. • Los síntomas cognitivos de la depresión. • Depresión en demencia diagnosticada previamente. • Evaluación clínica del paciente con depresión y demencia. • Manejo del paciente con depresión y demencia.
    35. 35. Frecuencia de síntomas psicológicos y conductuales en la evolución de la demencia de EA Jost BC, Grossberg GT. J Am Geriatr Soc. 1996;44:1078-1081 Meses Antes/Después de Diagnóstico -40 -30 -20 -10 0 10 20 30 Frecuencia(%dePacientes) 100 80 60 40 20 0 Agitación Alteración Ritmo Diurno Irritabilidad Conducta motora aberrante Agresividad Alucinaciones Cambio Humor Socialmente Inaccesible Delusiones Sexualmente Inapropriado Acusatorio Ideación Suicida Paranoia Depresión AnsiedadAislamiento Social
    36. 36. Prevalencia de SPCDs de muestras de pacientes en comunidad evaluados con NPI en 3 estudios europeos MAASBED (N=199) MMSE 15-28 REAL-FR (N=255) MMSE 11-20 REAL-FR (N=244) MMSE-21-30 EADC (N=138) MMSE 4-28 Promedio N=836 Delusiones 34.7 24.7 10.2 19.4 22.0 Alucinaciones 13.1 7.8 5.7 7.9 8.5 Agitación 28.6 44.3 32.8 30.9 35.0 Depresión 57.3 42.7 36.9 45.3 44.9 Ansiedad 39.2 46.3 44.3 33.8 42.0 Euforia 7.0 9.8 4.5 5.0 6.8 Apatía 59.3 63.5 47.9 48.9 55.5 Desinhibición 12.6 13.3 10.2 14.4 12.4 Irritabilidad 39.7 25.0 28.3 31.7 30.6 Conducta motora aberrante 34.7 29.8 14.7 18.7 24.7 Sueño 18.1 12.9 13.5 12.9 14.3 Apetito 24.6 24.3 20.5 12.9 21.4 Robert PH, et al. European Psychiatry 2005;20:490-496
    37. 37. Steinberg M, et al. Int J Geriat Psychiatry 2008;23:170-177 Prevalencia a 5 años de SPCDs en EA: Cache County Study
    38. 38. Prevalencia de SPCDs en un estudio de población, Inglaterra: England y Wales Savva GM, et al. Br J Psychiatry 2009;194:212-219 MRC-CFAS 13,004 individuos > 65 años Cambridgeshire Gwynedd Newcastle upon Tyne Nottingham Oxford Demencia: 587 No demencia: 2,050 MMSE, AGECAT, GMS, CAMDEX Entrevista estructurada SPCDs
    39. 39. Prevalencia de SPCDs en la evaluación basal del Medical Research Council-Cognitive Function and Ageing Study Síntomas Participantes sin demencia (n=2050) Participantes con demencia (n=587) p Apatía 12.1 50.3 <0.001 Problema de Sueño 43.8 42.0 0.574 Irritabilidad 12.8 28.8 <0.001 Persecusión 8.1 25.4 <0.001 Depresión 8.6 20.5 <0.001 Falsas identificaciones 3.0 20.3 <0.001 Alucinaciones 3.7 15.1 <0.001 Conducta Motora Aberrante 0.3 12.8 <0.001 Ansiedad 6.3 8.9 0.068 Savva GM, et al. Br J Psychiatry 2009;194:212-219
    40. 40. Qué tanto se parecen apatía y depresión? Apatía Depresión Falta de Motivación Falta de iniciativa Indiferencia Desánimo Desesperanza Culpa y autocrítica Ideación suicida Síntomas vegetativos Falta de interés Falta de energía Falta de insight Lentitud psicomotora
    41. 41. Conforme progresa síndrome demencial, se superponen síntomas conductuales y trastornos del movimiento Depresión Trastornos del movimiento Psicosis Demencia
    42. 42. Una amplia gama de entidades nosológicas no pueden ser ignoradas por una buena anamnesis Depresión Trastornos del movimiento Psicosis Demencia Depresión con demencia (“pseudodemencia”) Demencia con depresión EP con depresión DEP, DCLewy, EA con movimientos involuntarios DEP, DCLewy, EA, DV con síntomas psicóticos Depresión Psicótica Esquizofrenia con depresión Esquizofrenia con deterioro cognitivo Esquizofrenia con trastornos del movimiento DEP, DCLewy, EP y deterioro cognitivo Enfermedades médicas & drogas Depresión Vascular DCL con depresión
    43. 43. Agenda • Depresión como factor de riesgo de demencia. • Depresión como síntoma inicial de demencia. • Los síntomas cognitivos de la depresión. • Depresión en demencia diagnosticada previamente. • Evaluación clínica del paciente con depresión y demencia. • Manejo del paciente con depresión y demencia.
    44. 44. J. T. Olin, et al. Am.J.Geriatr.Psych 2002;10(2):125-128. P. B. Rosenberg, et al. Int.J.Geriatr.Psychiatry 2005;20 (2):119-127. 1. Humor deprimido clínicamente significativo* 2. Afecto o placer positivo disminuido en respuesta a contacto social o actividades cotidianas 3. Aislamiento o retirada social 4. Disrupción en apetito 5. Disrupción en sueño 6. Cambios psicomotores** 7. Irritabilidad 8. Fatiga o pérdida de energía 9. Sentimientos de inutilidad, desesperanza o culpa 10.Pensamientos recurrentes de muerte o suicidio A. Al menos 3 de los siguientes: Criterios para el diagnóstico de depresión en el contexto de demencia de la EA Síntomas presentes al menos 2 semanas, que afectan al funcionamiento del paciente, y, al menos, uno de ellos es: 1. Humor depresivo o 2. Afecto o placer positivo disminuido.
    45. 45. J. T. Olin, et al. Am.J.Geriatr.Psych 2002;10(2):125-128. P. B. Rosenberg, et al. Int.J.Geriatr.Psychiatry 2005;20 (2):119-127. 1. Humor deprimido clínicamente significativo* 2. Afecto o placer positivo disminuido en respuesta a contacto social o actividades cotidianas 3. Aislamiento o retirada social 4. Disrupción en apetito 5. Disrupción en sueño 6. Cambios psicomotores** 7. Irritabilidad 8. Fatiga o pérdida de energía 9. Sentimientos de inutilidad, desesperanza o culpa 10.Pensamientos recurrentes de muerte o suicidio A. Al menos 3 de los siguientes: Criterios para el diagnóstico de depresión en el contexto de demencia de la EA No se incluirán síntomas relacionados claramente con otra enfermedad médica o que sean claramente síntomas no afectivos de la demencia (por ejemplo, pérdida de peso por dificultades en la ingesta).
    46. 46. J. T. Olin, et al. Am.J.Geriatr.Psych 2002;10(2):125-128. P. B. Rosenberg, et al. Int.J.Geriatr.Psychiatry 2005;20 (2):119-127. 1. Humor deprimido clínicamente significativo* 2. Afecto o placer positivo disminuido en respuesta a contacto social o actividades cotidianas 3. Aislamiento o retirada social 4. Disrupción en apetito 5. Disrupción en sueño 6. Cambios psicomotores** 7. Irritabilidad 8. Fatiga o pérdida de energía 9. Sentimientos de inutilidad, desesperanza o culpa 10.Pensamientos recurrentes de muerte o suicidio A. Al menos 3 de los siguientes: Criterios para el diagnóstico de depresión en el contexto de demencia de la EA B. Se reúnen todos los criterios para el diagnóstico de EA. C. Los síntomas causan disrupción clínicamente significativa en el funcionamiento D. Los síntomas no ocurren exclusivamente en el curso de un delirium E. Los síntomas no son debidos a los efectos fisiológicos de una sustancia F. Los síntomas no se deben a otros diagnósticos psiquiátricos mayores
    47. 47. • Evaluación breve para cribado de Depresión: – Inventario de Depresión de Beck-II. – Geriatric Depression Scale (Yesavage) de 15 ítems. – Escala de depresión de Cornell, cuando MMSE ≤ 18. – Sub-escala depresión/disforia del NPI. • Evaluación breve Neurocognitiva: – MMSE – ACE Evaluación clínica en sospecha de depresión en paciente con demencia
    48. 48. Cornell > 7 No deprimido. Reevaluar en 6 meses NO SI SI Fármacos? Suspender Cambiar de tratamiento Alcohol? NO SI Abstinencia Monitoreo NO Cornell > 7 SI Iniciar tratamiento No deprimido. Reevaluar en 6 meses NO Orientación diagnóstica y terapéutica de depresión en demencia según Escala de Cornell Documento de Consenso SEP-SEN 2012
    49. 49. Agenda • Depresión como factor de riesgo de demencia. • Depresión como síntoma inicial de demencia. • Los síntomas cognitivos de la depresión. • Depresión en demencia diagnosticada previamente. • Evaluación clínica del paciente con depresión y demencia. • Manejo del paciente con depresión y demencia.
    50. 50. Evidencia de eficacia de los antidepresivos (AD) en el tratamiento de depresión en demencia • Evidencia insuficiente sobre eficacia y seguridad de AD. • Escasos RCTs, de muestras pequeñas, y solo evaluaron algunos ISRS. • Los ATC tienen similar eficacia que ISRS, pero con mayor frecuencia de eventos adversos. • Modesta evidencia de eficacia antidepresiva para sertralina y citalopram. • Nuevas evidencias para citalopram en manejo de agitación y psicosis Bains J, Birks JS, Dening TR et al. Biblioteca Cochrane Plus 2008;2 Thompson et al. Canadian J Psychiatry 2007;52:248-255
    51. 51. Sertralina y Mirtazapina según variaciones en puntuación del Cornell Scale for Depression in Dementia (CSDD) Banerjee S, et al. Lancet 2011;378:403-411
    52. 52. Agente Dosis Comentario Fluoxetina Inicial: 10 mg/d Maximo: 20 mg/d Vida media prolongada. Efectos colaterales dependende tiempo. Paroxetina Inicial: 10 mg/d Maximo: 40 mg/d Efectos anticolinérgicos. Sertralina Inicial: 25 – 50 mg/d Maximo: 200 mg/d El mejor tolerado. Escasas interacciones. Citalopram Inicial: 10 mg/d Maximo: 40 mg/d Buena tolerancia. Náuseas y disturbios del sueño Escitalopram Inicial: 10 mg/d Maximo: 20 mg/d Buena tolerancia. Puede causar náuseas. Duloxetina Inicial: 20 mg BID Maximo: 30 -40 mg BID Sin evidencia aún en depresion-demencia. Documento de Consenso SEP-SEN 2012 Recomendaciones de dosis de inicio y mantenimiento de ADs en el tratamiento de depresión en demencia
    53. 53. Agente Dosis Comentario Nefazodona Inicial: 50 mg BID Maximo: 150-300 mg BID Mejora ansiedad. Hepatotoxicidad. Bupropion Inicial: 37.5 mg/d Incremento 37.5 c/3 d Maximo: 150 mg BID Evitar en pacientes con agitación o convulsiones. Mirtazapina Inicial: 7.5 mg/d Maximo: 30 mg/d Mejora sueño, apetito y aumento de peso. Venlafaxina Inicial: 37.5 mg BID Maximo: 225 mg/d Monitoreo de PA Documento de Consenso SEP-SEN 2012 Recomendaciones de dosis de inicio y mantenimiento de ADs en el tratamiento de depresión en demencia
    54. 54. El manejo del dolor juega un rol importante en el tratamiento de la agitación y la agresividad Husebo BS, et al. BMJ 2011;343:d4065
    55. 55. Escitalopram y risperidona con similar eficacia para reducir síntomas psicóticos y agitación en EA Barak Y et al, International Psychogeriatrics 2011;23(9):1515–1519
    56. 56. En EA, Citalopram reduce la agitación y carga del cuidador a expensas de efectos cardíacos y cognitivos Porsteinsson AP, et al. JAMA 2014;311(7):682-691
    57. 57. Manejo de depresión en demencia y enfermedad de Alzheimer: Conclusiones • Estrecha relación entre depresión y demencia: FR o pródromos? • DTE incrementa conversión de DCL a demencia de EA. • Hipótesis vascular podría explicar la relación depresión/demencia. • Diferenciar depresión de demencia en estadios iniciales es un “reto”. • “Seguimiento longitudinal” podría aclarar nuestras dudas. • En síntomas depresivos de demencia predominan síntomas somáticos. • Considere antidepresivos del tipo ISRS con escasos eventos adversos. • Algunos antidepresivos, también mejoran agitación y psicosis.
    58. 58. twitter.com/ipneurociencias instituto-peruano-de-neurociencias Facebook.com/ipneurociencias slideshare.net/ipneurociencias

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