Behaviour As Predictor of Dementia

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Most people with dementia undergo behavioral changes during the course of the disease. They may become anxious or repeat the same question or activity over and over. The unpredictability of these changes can be stressful for caregivers. As the disease progresses, your loved one's behavior may seem inappropriate, childlike or impulsive. Anticipating behavioral changes and understanding the causes can help you deal with them more effectively.

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Behaviour As Predictor of Dementia

  1. 1. Dr. Ennapadam.S. Krishnamoorthy MD., DCN, PhD (Lond), FRCP (Lond, Glas, Edin), MAMS (India) TS Srinivasan Chair in Clinical Neuroscience & Founder Director TRIMED I NEUROKRISH www.trimedtherapy.com I www.neurokrish.com Behavioral changes that predict early dementia
  2. 2. Neurobiology of Aging  Prefrontal, entorhinal, and temporal cortices are the most severely affected, whereas primary visual and somatosensory cortices might be more resistant to the influence of aging  All these affected areas are polymodal and association cortices of the limbic system which is involved in cognitive processes that include attention, working memory, and the control of behavior
  3. 3. Multimodal Neurobiological Mechanisms in the Aging Brain  Age-related changes in regional cerebral blood flow and glucose metabolism, including insular decline, have been demonstrated- role in processing sensory information  Imaging studies have documented a substantial decline in D1 and D2 receptors and dopamine transporters- associated with changes in motor as well as cognitive/ behavioral functions  Hippocampal volumes are strong predictors of memory performance in normal aging- Left hippocampal measurements especially delayed retention of verbal material are predictive of memory performance and as has been recently demonstrated, depression  Alterations in the white matter might represent the predominant neuroanatomic change in normal aging
  4. 4. ORBITOFRONTAL SYNDROME DISINHIBITION INAPPROPRIATE AFFECT IMPAIRED JUDGEMENT DISTRACTIBILITY
  5. 5. DORSOLATERAL SYNDROME EXECUTIVE FUNCTION DEFECTS PERSEVERATION STIMULUS-BOUND BEHAVIOUR DIMINISHED VERBAL FLUENCY
  6. 6. MEDIAL FRONTAL SYNDROME • APATHY • MUTISM • TRANSCORTICAL APHASIA • LOWER EXTREMITY PARESIS • INCONTINENCE
  7. 7. The limbic system & its connections
  8. 8. Geschwind’s Temporal Lobe Personality A behavioural syndrome described in temporal lobe epilepsy characterised by  intensified and labile emotionality  viscosity (orderliness, excessive attention to detail and persistence)  Hypo-sexuality  Hyper-religiosity  Hyper-graphia
  9. 9. GESCHWIND & KLUVER-BUCY HYPERCONNECTION  EMOTIONAL INTENSITY  VISCOSITY  HYPOSEXUALITY DISCONNECTION  PLACIDITY  HYPERMETAMOR- PHOSIS  HYPERSEXUALITY
  10. 10. Disinhibition Syndrome related terms: “emotional incontinence” “pathological emotionalism” “pseudobulbar affect” postulated cause  disconnection of frontal lobe control from limbic (emotional) brain regions
  11. 11. IEED- involuntary emotional expression disorder
  12. 12. Behavioral and Psychological Disturbances  Behavioral and psychological symptoms of dementia (BPSD) include non-cognitive symptoms and behaviors that commonly occur in patients with dementia. Lawlor B. Br J Psychiatry. 2002  They include psychotic symptoms, mood symptoms, aberrant motor behaviors, and inappropriate behaviors.  BPSD occurs due to both anatomical and biochemical changes within the brain. Psychological factors such as premorbid neuroticism and low frustration tolerance appear to predispose individuals to develop BPSD. McIlroy S, Craig D. Curr Alzheimer Res. 2004
  13. 13. Mild Behavioral Dysfunction
  14. 14. The advantages of early detection  Early detection of BPSD: - enables the clinician to identify and treat problem behaviors earlier - reducing patient suffering and prevent caregiver burnout - protect the patient’s social support structure - anticipate dementia?  There are several behavioral markers for earlier detection of Dementia and these are not limited to Alzheimer’s Disease  Behavioral markers have also been shown to be accurate in predicting the conversion from MCI to AD
  15. 15.  Patients diagnosed with mild cognitive impairment (MCI) present with a higher rate of NPS than healthy people  Moreover, in the MCI population, the risk of developing dementia is high when NPS are present  Patients with a diagnosis of mild behavioral impairment (MBI), even those with normal cognition, show a notably increased risk of progression to degenerative dementia
  16. 16. Depression as a predictor of MCI conversion to AD. Collins, 2013 c- ia al on ia r- ot al m- or re ng dementia during follow-up was 2.6 times greater if depression was present in MCI subjects at baseline.6 Another longitudi- nal study showed an increased presence of depression, from baseline status, in patients who developed cognitive impair- ment and dementia versus the control population with stable cognition and healthy patients,32 concluding that depressive symptoms are associated with cognitive decline. However, the importance of depression as a risk factor for developing dementia could not be demonstrated in other studies. 5,33 Butters et al34 propose that depression alters an indi- vidual’s risk of cognitive dysfunction, shortening the latent period between the development of AD neuropathology and the onset of clinical dementia, thus increasing the incidence and prevalence of AD among older adults with depression. Apathy (lack of motivation, diminished goal-directed submit your manuscript | www.dovepress.com Dovepress 1446 NPSin MCI Various empirical studies have been developed to investigate NPS in MCI. Table 2 summarizes data from the last 3 years. Depression is the most studied symptom in MCI and dementia.The most frequent depressive symptoms observed in these patients are irritability, impairment of attention and concentration, paranoid and obsessive thoughts, lack of insight, psychomotor retardation, and weight loss. The prevalence of depressive symptoms may be as high as 45%.31 In a large prospective study, the possibility of converting to to an an D v fo o th 1
  17. 17. Sleep as a predictor?  REM Behavior Disorder (RBD) can be early marker for development of neurodegenerative diseases.  RBD is characterized by the acting out of dreams that are vivid, intense, and violent. Dream-enacting behaviors include talking, yelling, punching, kicking, sitting, jumping from bed, arm flailing, and grabbing.  More than half of those with RBD will eventually exhibit signs and symptoms of a neurodegenerative neurological disorder gradually over months or years. Vyas U, BJMP 2012
  18. 18. Apathy as a predictor  Apathy (lack of motivation, diminished goal directed behavior, decreased emotional engagement) is seen is as many as one-third of all patients with MCI. Apostolova LG & Cummings JL. Dement. Geriatr Cogn Disord 2008; 25(2):115-126  Persons with mild cognitive impairment were more likely to convert to AD a year later if they also had apathy. Robert, Clin Neurol Neurosurg. 2006  One European study showed a 7 fold risk of conversion from Amnestic MCI to AD when Apathy was a core symptom. Palmer K. J Alzheimers Dis 2010;20(1); 175-183
  19. 19. Anxiety as a predictor  Anxiety, defined as excessive apprehension and a feeling of foreboding is the third most common BPS  Demey found that 37% of all patients with MCI had anxiety when compared with 5% of the control group (Vertex 2007; 18(74): 252-57)  People with MCI & anxiety were found in a 3 year study to have a higher risk predictor of progression to AD (Palmer K. Neurology 2007; 68(19): 1596-1602
  20. 20. Other BPS in MCI  Irritability has been reported to be as common as 20% of all patients with MCI in a large community based study (Geda et al. Arch Gen Psych 2008; 65(10): 1193-98  Other symptoms like agitation, delusions & psychotic symptoms may be markers of rapid cognitive decline and represent major risk of developing dementia
  21. 21. Behavioral correlates of FTD  Executive dysfunction with prominent behavioral symptoms  Early:  Set aside personal and professional responsibilities  Lose empathy for others  Unaware of goings on in their environment  Cannot perceive complex social emotions: shame, guilt, pride, embarassment  Late  Disinhibition  Apathy  Dramatic changes in personal care: personal hygiene & dressing  Hyper-orality, Hyper-metamorphosis, altered eating behavior, hypersexuality (Kluver-Bucy syndrome)  Affective disorder, visual and auditory agnosia, anosognosia
  22. 22. Hypersexual Behavior  Hypersexual behavior may be a particular feature of behavioral variant frontotemporal dementia (bvFTD), which affects ventromedial frontal and adjacent anterior temporal regions specialized in interpersonal behavior.  On comparing the behavior with AD, it has been found that it is uniquely associated bvFTD. Mendez & Shapira. Arch Sex Behav. 2013
  23. 23. Are there sensitive time periods for dementia caregivers? The occurrence of behavioral and psychological symptoms in the early stages of dementia K. A. Ornstein1,2, J. E. Gaugler3, D. P. Devanand4,5, N. Scarmeas5, C. W. Zhu1, and Y. Stern5 1Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA 2Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA 3School of Nursing, University of Minnesota, Minneapolis, Minnesota, USA 4Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York, New York, USA 5Taub Institute and the Department of Neurology, Columbia University Medical Center, New York, New York, USA Abstract Background—The behavioral and psychological symptoms associated with dementia (BPSD) Published in final edited form as: Int Psychogeriatr. 2013 September ; 25(9): 1453–1462. doi:10.1017/S1041610213000768. that occur during early stage dementia with subsequent caregiver depressive symptoms. Methods—Patients were followed from the early stages of dementia every six months for up to 12 years or until death (n = 160). Caregiver symptoms were assessed on average 4.5 years following patient’s early dementia behaviors. A generalized estimating equation (GEE) extension of the logistic regression model was used to determine the association between informal caregiver depressive symptoms and BPSD symptoms that occurred at the earliest stages dementia, including those persistent during the first year of dementia diagnosis. Results—BPSD were common in early dementia. None of the individual symptoms observed during the first year of early stage dementia significantly impacted subsequent caregiver depressive symptoms. Only patient agitation/aggression was associated with subsequent caregiver depressive symptoms (OR = 1.76; 95% CI = 1.04–2.97) after controlling for concurrent BPSD, although not in fully adjusted models. © International Psychogeriatric Association 2013 Correspondence should be addressed to: K. A. Ornstein, Brookdale Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Phone: 212-659-5555; Fax: 212-849-2566. katherine.ornstein@mssm.edu. Conflict of interest None. Conclusions—Persistent agitation/aggression early in dementia diagnosis may be associated with subsequent depressive symptoms in caregivers. Future longitudinal analyses of the dementia caregiving relationship should continue to examine the negative impact of persistent agitation/ aggression in the diagnosis of early stage dementia on caregivers. eywords in et al.
  24. 24. Table 2 Neuropsychiatric symptoms in mild cognitive impairment. Datareviewed from 2010 to 2012 Study Patients Objective Conclusions Somme et al87 132 To identify NPSthat predict the progression from a-MCI to dementiausingan easy-to-administer screeningtool for NPS Faster progression to dementiawas observed in patients with either night-time behavioral disturbance, apathy, or anxiety as well as in those with ahigher number of items affected Peters et al88 230 To examine the association of NPSseverity with risk of transition to all-cause dementia, AD and VaD The presence of at least one NPSwas arisk factor for all-cause dementia, as was the presence of NPS with mild severity. Night-time behaviors were arisk factor for all-cause dementiaand of AD, whereas hallucinations were arisk factor for VaD Shahnawaz et al89 767 To study the prevalence and characteristics of depressive symptoms in MCI Individuals with MCI symptoms, when compared especially with a-MCI, express more depressive symptoms than cognitively intact individuals. These fin d i ngs hi ghl ight the imp or tance of assessi ng and treatingdepressive symptoms in MCI Richard et al90 397 To investigate if apathy predicts the progression from MCI to AD Symptoms of apathy, but not of depressive affect, increase the risk of progression from MCI to AD. Apathy in the context of symptoms of depressive affect does not increase this risk. Symptoms of apathy and depression have differential effects on cognitive decline Lee et al91 243 To examine the neuroanatomical changes associated with depressive symptoms in MCI Depressive symptoms were associated with greater atrophy in AD-affected regions, increased cognitive decline, and higher rates of conversion to AD. Depression in individuals with MCI may be associated with underlyingneuropathological changes, including prodromal AD, and may be apotentially useful clinical marker in identifyingMCI patients who are most likely to progress to AD Gallagher et al92 161 To determine whether NPStrack existing measures of decliningcognitive and functional status or may be considered distinct and sensitive biomarkers of evolvingAlzheimer’s NPSand, in particular, anxiety symptoms are common in patients with MCI. In this sample, anxiety for upcomingevents and purposeless activity frequently co-occurred and were signific a nt cl ini cal pr edi ct or sd
  25. 25. to progress to AD Gallagher et al92 161 To determine whether NPStrack existing measures of decliningcognitive and functional status or may be considered distinct and sensitive biomarkers of evolvingAlzheimer’s pathology NPSand, in particular, anxiety symptoms are common in patients with MCI. In this sample, anxiety for upcomingevents and purposeless activity frequently co-occurred and were signific a nt cl ini cal pr edi ct or s of earlier conversion to AD. However, these fin d i ngs were not independent of cognitive status at baseline and therefore may be markers of severity rather than independent predictors of disease progression Chan et al93 321 To explore the association between NPSand risk of cognitive decline in Chinese older persons residingin the community Depression in non-demented older patients may represent an independent dimension refle c t ing earl y neuronal degeneration. Further studies should be conducted to assess whether effective management of NPSexerts benefic i al ef fect s on cogni tive funct ion Ryu et al94 220 To determine the persistence of NPSover 6 months in participants with MCI NPSwere highly persistent overall in older people with MCI. Persistence was predicted by havingmore severe symptoms at baseline. Clinically signific a nt levels of NPSwere associated with decreased quality of life. We conclude that clinicians should be aware that NPSsymptoms in MCI usually persist Palmer et al5 131 To evaluate whether depression or apathy in patients with a-MCI increases the risk of progressingto AD Apathy, but not depression, predicts which patients with a-MCI will progress to AD. Thus, apathy has an important impact on a-MCI and should be considered amixed cognitive/psychiatric disturbance related to ongoingAD neurodegeneration Ramarkers et al95 263 To investigate the predictive accuracy of affective symptoms for AD duringafollow-up study in subjects with MCI, and whether the predictive accuracy was modifie d by age, the presence of a-MCI or the length of follow-up Affective symptoms are associated with adecreased risk for AD. The risk may be dependent on MC I subtype or length of follow-up, but it does not depend on age Abbreviations: AD, Alzheimer’sdisease; a-MC I, amnestic mild cognitive impairment; NPS, neuropsychiatric symptoms; VaD, vascular dementia.
  26. 26. Take home messages  A range of neuropsychiatric symptoms (NPS) also called behavioral & psychological symptoms (BPS) underlie MCI and dementia  Depression, apathy and anxiety have specific importance in predicting the conversion of amnestic MCI to AD  Irritability is seen in about 20% of patients and may be more prevalent in multi-domain MCI  NPS/BPS can be correlated with various neurobiological changes seen in imaging and are reflective of the ongoing neurodegenerative process  NPS/ BPS (like cognitive decline) are core symptoms of dementia and need to be better researched.
  27. 27. Thank You for your attention

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