Published on

  • Be the first to comment

  • Be the first to like this

No Downloads
Total Views
On Slideshare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

  1. 1. Review document for investigation and management of cognitive impairment and dementia Definition Mild cognitive impairment (MCI) is defined as cognitive decline greater than expected for an individual’s age and education level that does not interfere notably with activities of daily living (ADLs). Not all patients with MCI progress to dementia, but more than 50% will. Dementia is a clinical diagnosis made when acquired cognitive deficits in more than one area of cognition interfere with ADLs and represent a decline from a previously higher level of functioning. Types of dementia The common dementia syndromes are tabulated below. This document focuses on dementia in general, with attention given to Alzheimer's and vascular dementia. Type Recommended diagnostic criteria Sensitivity/specificity Alzheimer's disease (DAT) NINDS/ADRDA criteria (McKhann 1984) Sensitivity 83%, Specificity 48% (Knopman 2001) Vascular dementia (VaD) NINDS-AIREN criteria (Roman 1993) Sensitivity 50%, Specificity 85% (Gold 2002) Dementia with Lewy- body (DLB) International Consensus criteria for DLB (McKeith 1996) Sensitivity 50% Specificity low (Litvan 2003, McKeith 2005) Frontotemporal dementia (FTD) Lund-Manchester criteria (Neary 1998), NINDS criteria for FTD (McKhann 2001) Neither validated against autopsy It can be difficult to differentiate between the different types of dementia clinically. In practice, mixed dementia is common. Dementia related to alcohol excess should be kept in mind although there are no widely accepted standardized diagnostic or neuropathological criteria. More rare forms of dementia include Creutzfeldt-Jakob disease, primary non- fluent aphasia and dementia due to neurosyphilis. SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 1/20
  2. 2. Disease historical perspective In 1901, Dr. Aloysius Alzheimer, a German psychiatrist and neuropathologist first described a case of presenile dementia in a 51-year-old woman in a German asylum. Five years later, he gave the first description of the disease association with amyloid plaques and neurofibrillary tangles on post-mortem brain tissue. Hachinski et al in 1974 described multi-infarct dementia, a clinical syndrome related to multiple small vessel infarcts in the brain. Disease burden on our society There are currently an estimated 40,000 people in Ireland with dementia. Approximately 90% of these are over the age of 65. In 2008, there will be approximately 4,000 new Irish dementia cases. Dementia also affects the lives of nearly 50,000 people in Ireland who are involved in caring for someone with dementia. Worldwide the number of dementia sufferers is estimated at 29.8 million. (Alzheimer's Society website) SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 2/20
  3. 3. Health Economics In 2006, the cost of dementia in Ireland was estimated at €400m. Less than 10% of this cost is attributed to community care. However family carers provide 57% of the value of informal care in the community without receiving financial remuneration. This undeclared hidden cost should be included in all estimates of disease burden. In 2005, the cost of dementia worldwide was estimated to be US$315.4 billion, of which US$105 billion (37%) was for informal care (Alzheimer's Society Ireland website) Future disease trends Ireland’s demography is changing and as an increased proportion of the population lives beyond their seventh decade, this will also be reflected in an increased prevalence of neurodegenerative disease in general and in the dementia syndromes in particular. Estimates suggest a prevalence of 104,000 cases by 2037. This reflects an increase of 300% while population expansion as a whole is expected to be in the region of 40%. Worldwide, it is estimated that the number of patients with dementia will double every 20 years to 81.1 million by 2040. (Alzheimer's Society Ireland website) Aetiology and Risk Factors Non-modifiable risk factors • Age - The risk of developing dementia increases with age. It is unclear whether age is a risk factor in its own right or reflects the increasing time during which other risk factors may exert their influence. DAT prevalence in one European study of community dwelling adults was 0.6% in those aged 65-69 rising to 22% in those aged 90-years and over (Lobo 2000). • Gender - Prevalence studies describe higher rates of dementia in women than men, especially for DAT (Rocca 1991). In part, this approximate difference in prevalence of 2:1 between women and men is due to women generally living longer. Rates for VaD are higher in men, though women tend to catch up at older ages. • Family History and Genotype - A person with a positive family history of dementia may be at increased risk of developing dementia although the odds ratio is not well documented. When both parents have a clinical diagnosis of DAT, dementia risk in offspring is 31% at age over 60 and 41% at age over 70 (Jayadev 2008). SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 3/20
  4. 4. The Apolipoprotein E (ApoE) ὲ4 allele located on Chromosome 19 has been identified as a risk factor for development of late onset DAT and reduces the age at which one could expect to develop the condition (Strittmatter 1993). However the effect is not equal across all racial groups. Possession of ApoE ὲ4 alone is not causative of DAT but modulates the age of onset and likelihood of the disease-becoming manifest under the influence of other aetiological factors. Several autosomal dominant forms of young-onset Alzheimer's disease have been described including mutations in the amyloid precursor protein, presenilin-1 and presenilin-2 genes. Such cases are rare and characteristically patients have an age of onset of below 55 years. The risk of developing DAT is significantly higher in patients with Down's syndrome. In one North American study, DAT prevalence in institutionalized Down's syndrome patients was 55% in patients aged 50-59 and 75% in those aged 60-years and above, reflecting both an earlier age of disease onset and higher disease prevalence (Lai 1989). Familial autosomal dominant inheritance has also been shown in frontotemporal dementia. Other rare forms of inheritable dementia include cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Huntington's disease. SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 4/20
  5. 5. Modifiable risk factors • Cardiovascular risk factors - Cardiovascular risk factors including smoking, hypertension, diabetes mellitus and hyperlipidaemia are independent risk factors for development of VaD. They promote atherosclerosis, which is associated with development of all dementia types. One cross-sectional study found all indicators of atherosclerosis (vessel wall thickness, plaques of the carotid arteries, and the ratio of ankle-to- brachial systolic blood pressure) to be associated with all dementias, with odds ratios ranging from 1.3 to 1.9. (Hofman 1997). It is recommended that established cardiovascular risk factors be treated to reduce the risk of developing dementia and to reduce the possibility of progression of mild cognitive impairment to dementia. • Alcohol - Excessive alcohol consumption is an established risk factor for dementia. It is difficult to quantify or define the threshold of excessive alcohol consumption. Saunders described a five-fold risk of developing a psychiatric disorder including depression and dementia after the age of 65 in men with a history of five years or more of heavy alcohol consumption at any stage of life (Saunders 1991). Epidemiological cross-sectional and longitudinal prospective studies suggest a protective effect of moderate alcohol consumption (1-3 drinks per day) in unspecified dementia and DAT. Peters’ systematic review and meta-analyses of alcohol and dementia studies suggests that low to moderate alcohol consumption may reduce risk for DAT by 32% (Peters 2008) when compared with abstinence or heavy consumption (greater than three drinks per day). Methodological study weaknesses include a lack of standardization of alcohol volume measurement. Optimal consumption amounts were more than two drinks per week up to three drinks/250-500 ml per day. No evidence supports the protective effect of one type of alcoholic drink over any another. However, these associative studies should not be a basis on which to advise consumption of alcohol as a protective measure against dementia (Letenneur 2004). • Education and mental stimulation - There is some evidence that a low education level is associated with subsequent development of dementia (Valenzuela 2005). Interpretation of whether this represents a true increased risk, or reflects an alteration of the threshold at which dementia becomes apparent, is uncertain. Several studies describe a decreased rate of subsequent DAT development in subjects participating in common cognitively demanding leisure activities such as reading, playing board games and playing musical instruments (Wilson 2002, Verghese 2003). However, these findings are also compatible with the ‘cerebral reserve’ hypothesis, whereby those of higher ability, who are consequently more likely to engage in mentally stimulating activities, are also at decreased risk of subsequently developing dementia. Whilst there are many reasons to encourage engagement in such activities, further studies to assess possible protective effects of cognitive activities on risk of dementia are needed. SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 5/20
  6. 6. Exercise – Limited evidence describes a protective effect of exercise on DAT development. Physical activity in mid-life (defined as lasting 20–30 minutes causing breathlessness and sweating) at least twice weekly has been associated with a 50% reduction in risk of developing dementia and DAT (Rovio 2005). Features in history and examination Detection Patients may self refer with subjective memory complaints. These should be taken seriously as they have been shown to be predictive of dementia. These symptoms are however also associated with depression and anxiety disorders. Family members and friends, the general practitioner, nursing or social care staff may be the first to recognise changes in cognition, emotion or capabilities that signify possible early dementia. The collateral history of cognitive impairment and its impact on patient function is crucial in establishing the diagnosis. A third route to recognition is through revelatory moments, for example, when the sudden incapacity of a carer reveals the dementia processes in the patient. Patients in such instances often present as crisis admissions through the emergency services. History A detailed history from the patient and collateral history from a close relative or carer is paramount in the assessment of suspected cognitive impairment/dementia. Attention should be paid to • Mode of onset (when, where noticed) • Course of progression (rate, fluctuation) • Pattern of cognitive impairment (disorientation, poor short term memory, repetitive) • Presence of non-cognitive symptoms (behavioural disturbance, hallucinations, delusions, wandering, hoarding, anxiety, aggression, shouting, sexual disinhibition) • Review of medications that can potentially impair cognitive function • Presence of signs/symptoms of depression and anxiety A detailed physical examination should be performed, in particular, looking for focal neurology, motor features of parkinsonism, signs indicative of vascular disease and hypothyroidism. The presence of co morbid depression should be considered and assessed routinely. Clinical phenotypes for different dementia syndromes Dementia of Alzheimer’s type (DAT) (50 to 60%) DAT represents the commonest dementia syndrome. The average survival period after diagnosis is 8 to 10 years. SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 6/20
  7. 7. Common symptoms in early disease include • Memory problems e.g. poor short term memory, disorientation, repetition, difficulty with new memory learning • Progressive deterioration in the ability to perform basic ADLs • Behaviour changes, mainly apathy and social withdrawal, but also behavioural disturbances Vascular dementia (VaD) (15 to 20%) • In some cases there may be a direct chronological relationship between discrete significant cerebrovascular events and the onset of cognitive impairment. • Patients may present with signs of stroke or other vascular problems e.g. ischaemic heart disease or hypertension. • Onset may be abrupt, with periods of sudden decline followed by relative stability. • Physical problems such as urinary incontinence, decreased mobility and balance problems are more commonly seen in people with vascular dementia (VaD) than in people with Alzheimer’s disease. Hachinski Ischaemic Score The Hachinski Ischaemic Score (HIS) represents a brief clinical tool helpful in the “bedside” differentiation the commonest dementia types, DAT and VaD. It’s utility has been validated by meta-analysis in pathologically verified patients with dementia. A cut-off score ≤ 4 for DAT and ≥ 7 for VaD has a sensitivity of 89% and a specificity of 89% (Moroney 1997). It is not useful in determinations between mixed dementia and other dementia types. Item No. Description Value 1 Abrupt onset 2 2 Stepwise deterioration 1 3 Fluctuating course 2 4 Nocturnal confusion 1 5 Preservation of personality 1 6 Depression 1 7 Somatic complaints 1 8 Emotional incontinence 1 9 History of hypertension 1 10 History of stroke 2 11 Associated atherosclerosis 1 12 Focal neurological symptoms 2 13 Focal neurological signs 2 HIS items distinguishing VaD from DAT were stepwise deterioration (odds ratio (OR), 6.06), fluctuating course (OR, 7.60), hypertension (OR, 4.30), history of stroke (OR, 4.30) and focal neurological symptoms (OR, 4.40). SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 7/20
  8. 8. Dementia with Lewy bodies (DLB) (5 to 10%) Characteristic features of DLB include: • Fluctuation of awareness from day-to-day. • Signs of parkinsonism such as tremor, rigidity and slowness of movement or poverty of expression. • Visual hallucinations or delusions occur frequently. • Falls are also common. DLB has a similar pathological basis to Parkinson’s disease dementia and both are associated with progressive cognitive decline and parkinsonism. Approximately three quarters of people with Parkinson’s disease develop dementia after 10 years. Fronto-temporal dementia (FTD) (5 to 10%) FTD is uncommon by comparison to DAT or VaD but represents a significant proportion of people who present with dementia under the age of 65. Changes in behaviour early in disease include disinhibition, lack of judgement, loss of social awareness and loss of insight and are much more common than memory problems. Disturbance of mood, speech and continence are frequent. A positive family history of a similar disorder is not uncommon. Mixed dementias (20 to 30%) Mixtures of two or more of the active dementias can be found in the same person with one or other phenotype usually dominating. Studies suggest that the interaction between vascular disease and the core features of Alzheimer’s disease is extremely complex and that rigid boundaries between subtypes of dementia may be unduly artificial. Response to treatment or side effects from treatment in people with mixed dementia may be different from those in people with a specific diagnosis. Diagnosis of delirium A short section is included here with regard to the diagnosis of delirium due to the importance of excluding delirium when assessing a person with cognitive problems. Please refer to the reference document SVUH_MedEl_DeliriumReferencedoc_2008 for more complete information. Delirium is more common in the older person, with multiple medical co morbidities and underlying dementia. Delirium is defined as disturbance of consciousness accompanied by change in cognition that is not better accounted for by a pre- existing dementia. Assessment must include a detailed history, physical examination and performance of appropriate investigations. These may include blood tests, radiological investigations, urine analysis, electrocardiograph (ECG) and lumbar puncture if central nervous system infection is suspected. Delirium is associated with negative outcomes including higher rates of death, poorer function and lower MMSE test sores 2 years after discharge from hospital (Francis 1992). SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 8/20
  9. 9. Evidence base for investigations It must be stressed that formal neuropsychological assessment remains the gold standard in defining the nature and extent of cognitive deficits. Local access to formal neuropsychological assessment is by referral to the Old Age Psychiatry service. Cognition screening tools • The Mini-Mental State Examination (MMSE) was developed as a screening instrument for dementia and is widely used. The sensitivity of the MMSE ranges from 71% to 90% and specificity from 56% to 96% in primary care depending on the age of the patient, educational level and cut-off score employed (Boustani2003). The brevity of the MMSE (30 points test) results in a superficial assessment of memory, language, and visuo- perceptual function. Processing speed and executive function are not tested. Evidence from a systematic review has shown that the MMSE is suitable for the detection of dementia in individuals with suspected cognitive impairment. Potential limitations include association with level of education and sensitivity to depression. It may also be misleading in individuals with either high or low premorbid ability and with certain types of dementia (especially VaD, DLB and FTD). • The clock-drawing test is a simple and useful tool for assessing praxis and executive function (Sunderland 1989). It may be used in combination with the MMSE. It consists of asking the patient to draw a clock face, complete with numbers and filling in the time using the long and short hands at a specified time. A number of different scoring systems exist for this test (Brodaty 1997). • The Addenbrooke’s Cognitive Examination-Revised (ACE-R) examines cognitive function more comprehensively. It also incorporates the MMSE. It is a 100-point test battery assessing six cognitive domains, including attention, orientation, memory, verbal fluency, language and visuo-spatial ability. The sensitivity of the ACE-R with a cut-off score of 88 is 94% with a specificity of 89%. When a cut-off score of 82 is used the sensitivity is 84% with a specificity of 100%. (Mioshi 2006). A benefit of these and similar tools is that they can be administered in a short period of time by a clinician, specialist nurse or occupational therapist. Blood tests Blood tests are done to exclude a potential reversible or modifying cause of dementia and also to help exclude common misdiagnoses including delirium. The investigations described below do not reflect an exhaustive list: • Routine haematology • Biochemistry tests (electrolytes, calcium, glucose, renal and liver function) • Thyroid function tests • Vitamin B12 and folate levels SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 9/20
  10. 10. • Consider syphilis serology, genetic testing for Huntington’s disease, and H.I.V. serology as appropriate to the clinical setting. Brain imaging Structural imaging is used to exclude other cerebral pathologies (e.g. space-occupying lesions, normal pressure hydrocephalus) and to help establish the dementia type. However, sensitivity and specificity of structural imaging can vary and a systematic review found most had poor sensitivity and low specificity (Gifford 2000). MRI is preferred to assist with early diagnosis and to detect subcortical vascular changes. MRI may be used to quantify global cortical volumetric loss and to determine if there is disproportionate regional atrophy in the medial temporal lobe and hippocampus areas. CT scanning could also be used. Functional imaging where available such as single-photon emission computed tomography (SPECT) or fluoro-deoxy- glucose positron emission tomography (FDG-PET) may be useful in differentiating between AD, VaD and FTD (Dougall 2004, Mosconi 2005). Dopaminergic iodine-radio labelled (FP-CIT) SPECT may be used to aid in diagnosis of DLB (O'Brien 2004). Other investigations • Electrocardiograph (ECG) should be performed, looking for conduction delays if use of acetylcholinesterase inhibitors (AChEI) is being considered. • Cerebrospinal fluid (CSF) is not routinely examined unless Creutzfeldt-Jakob Disease (CJD) or other forms of rapidly progressive dementia are suspected. Protein 14-3-3 is associated with rapid neuronal loss and has high predictive value (>90% sensitivity and specificity) for CJD (Hsich 1996). • Electroencephalograph (EEG) is not used routinely in the diagnosis of dementia as the resting EEG often describes non-specific diffuse abnormalities. EEG is useful if disorders such as delirium (gross-slowing), fronto- temporal dementia (normal) or CJD (triphasic spikes) are suspected. • Urinalysis should be performed to outrule possible delirium secondary to infection. Disclosure of diagnosis and supports available Healthcare professionals should • Ask assessed patients if they wish to be informed of a diagnosis of dementia and with whom the diagnosis should be shared. • Seek formal permission where possible to disclose diagnosis to carers. • Be aware that many patients with dementia can understand their diagnosis, receive information and be involved in decision making. SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 10/20
  11. 11. • Be aware that some patients with dementia may not wish to know their diagnosis. A healthcare professional skilled in communication or counselling should give the diagnosis of dementia. Disclosure to patients may be considered unhelpful if cognitive deficits limit their ability to understand the meaning and implications of their diagnosis. Diagnosis disclosure can lead to mixed reactions, such as shock, distress, ambivalence or confirmation of existing suspicions. Where diagnosis is not disclosed there should be a clear record of the reasons. It is important to explain to patients and family that in many cases, the definitive diagnosis of the subtype of dementia may not be possible until or unless post-mortem examination is performed. The sensitivity and specificity of the various cognitive tests, neuro-imaging and diagnostic criteria can be discussed if necessary. The patient and family should be given information on • Course and prognosis of cognitive impairment/dementia • Interventions available • Services and social supports available in the community • Sources of financial and legal advice and advocacy • Medico-legal issues including driving Information given to patient and family should be recorded in the medical notes. Where possible, it is always best to provide care for patients with dementia in their own home environment. Encourage the patient and family to avail of local social supports such as public health nurse visits, attendance at a local day centre, delivered meals, personal alarm monitoring service and respite services. The issue of extended nursing care should be brought up as appropriate during the discussion on course and prognosis of dementia. Patients with mild cognitive and family should be advised to seek legal advice with regard to matters such as enduring power of attorney and making of wills. Driving & dementia Deliberations about driving should be made taking the level of cognitive function into consideration. This assessment should include a full history (including a collateral driving history), multidisciplinary assessment (cognitive testing including tests for executive dysfunction, visuo-spatial and perceptual deficits) and possibly an appropriate on-road test. A physical examination for focal weakness or visual field deficits as well as a history of seizures should be documented in the clinical notes. If family members express serious concerns over incidences while driving, the cessation of driving should be advised. Where an incident is associated with an acute illness or episode of decompensation, it is reasonable to follow the above plan of assessment once the episode has resolved. Cautious but reasonable general advice could include suggesting that patients with dementia who have not experienced any problems driving might confine their driving to their own locality and only during day light hours. SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 11/20
  12. 12. Social factors that need to be taken into consideration with regard to driving include the availability of an alternative form of transportation and the social support network of the patient. It is often necessary to stress the importance of driving cessation and emphasize the advice with a letter to the patient and the general practitioner. Evidence suggests that in the first 2 years of dementia, the risk of driving approximates that of the general population (Drachmann 1993). A case controlled study of crashes and dementia showed no increase in crash rates for drivers with dementia (Trobe 1996). Likely causes for these findings include lower mileage and restriction of driving by patient, family and doctor. A study showed that drivers with dementia who drive accompanied have fewer crashes than those who drive alone. (Bedard 1996). These findings are important as many doctors assume that dementia is an absolute contraindication to driving. Dementia is a heterogeneous condition and its effects on the driving task are complex. For example, it was found that 10% of patients had deteriorations in driving skills in the early stages of dementia (O'Neill 1992). Consequently the determination on driving ability in the presence of dementia should include the above systematic assessment or similar assessment method (O'Neill, Oxford textbook of Geriatric Medicine). Therapeutic Interventions No curative therapies for any of the dementia syndromes currently exist. Interventions may be non-pharmacological or pharmacological. The principal aims of interventions are • Promotion of independence and maintenance of function. • Management of non-cognitive symptoms and challenging behaviour. • Reduction of co morbid emotional disorders. Non-pharmacological interventions The onset of non-cognitive symptoms or challenging behaviour in patients with dementia, should prompt patient re- assessment to attempt to identify aggravating factors, including • Physical health • Depression • Possible undetected pain or discomfort • Side effects of medication • Individual biography • Psychosocial factors • Environmental factors Depending on availability, consider options including aromatherapy, therapeutic use of music and/or dancing, animal- assisted therapy & massage. SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 12/20
  13. 13. Pharmacological interventions Acetylcholinesterase inhibitors Alzheimer's disease (DAT) is associated with loss of cholinergic neurones in certain parts of the brain. Donepezil (Aricept®) is a reversible inhibitor of acetylcholinesterase. Rivastigmine (Exelon®) is a reversible inhibitor of acetylcholinesterase and butyrylcholinesterase. Galantamine (Reminyl®) is a reversible inhibitor of acetylcholinesterase and also has nicotinic receptor agonist properties. The AChEI group of drugs reduce enzymatic breakdown of acetylcholine thus increasing the concentration of acetylcholine released by intact cholinergic neurones, thereby facilitating cholinergic neurotransmission. Acetylcholinesterase inhibitors (AChEI) donepezil, galantamine and rivastigmine are licensed for the symptomatic treatment of mild to moderately severe Alzheimer’s disease. The results of 10 randomized, double blind, placebo controlled trials demonstrated that 6 months treatment with the above AChEIs at the recommended dose for people with mild, moderate or severe dementia due to Alzheimer’s disease produced improvements in cognitive function, on average -2.7 points (95%CI -3.0 to -2.3, p<0.00001), in the 70 point Alzheimer's disease Assessment (ADAS-Cog) Scale (Birks 2006). Benefits of treatment were also seen on measures of activities of daily living and behaviour. None of these treatment effects were large. Only rivastigmine is currently licensed for the symptomatic treatment of patients with dementia in Parkinson's disease. Rivastigmine appeared to have clinically meaningful benefit in approximately 15% of patients with dementia in Parkinson's disease (Maidment 2006). Tolerability of rivastigmine in particular nausea, vomiting and tremor are problematic. No other drug is currently licensed for VaD, DLB, FTD or other dementias (subcortical or mixed dementias). Evidence of efficacy of donepezil for people with mild or moderate vascular cognitive impairment is limited. Commonly however, the AChEIs and memantine are currently prescribed in dementia other than Alzheimer’s type, at clinical discretion without licence. There is no evidence to support the use of AChEI for patients with MCI. The putative benefits are minor, short lived and associated with significant side effects. AChEIs should be offered to patients with moderate DAT, in general with MMSE scores of 10 to 20. AChEI treatment should also be considered when there is a requirement to modulate the behavioural symptoms of dementia. Healthcare professionals should not rely on the MMSE score in patients who: • Score greater than 20, but who have moderate dementia as judged by significant impairments in functional ability and personal and social function compared with premorbid ability • Score less than 10 because of a low premorbid attainment or ability or linguistic difficulties, but who have moderate dementia as judged by an assessment tool sensitive to their level of competence • Are not fluent in the language in which the MMSE is given • Have learning disabilities SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 13/20
  14. 14. Depending on the type of AChEI, it may be available in tablet, liquid or topical patch form. A specialist in dementia care should start treatment. The specialist should • Seek carers’ views on the condition of the person with dementia at baseline • Choose an AChEI keeping in mind the adverse-event profile, concordance issues, co morbidities, possible drug interactions and dosing profiles • Review MMSE score and global, functional and behavioural assessment every 6 months • Seek carers’ views on the condition of the person with dementia at follow-up • Continue treatment if the MMSE score remains at or above 10 points and global, functional and behavioural condition indicates worthwhile effect. Memantine L-glutamate is the main excitatory neurotransmitter in the central nervous system (CNS), implicated in neural transmission, learning, memory and neuronal plasticity. Enhancement of the excitatory action of L-glutamate may play a role in the pathogenesis of DAT. Memantine (Ebixa®) is a low-affinity N-methyl-D-aspartate (NMDA)-receptor antagonist that may prevent excitatory amino acid neurotoxicity without interfering with the actions of glutamate necessary for learning and memory. Memantine is licensed for moderate to severe DAT, were the evidence supports a small beneficial effect at six months of treatment. This small beneficial effect was not detected in patients with VaD (McShane 2006). AChEI and memantine may be withdrawn if/when the treatment is deemed to be no longer beneficial. Treatments should only be withdrawn during an unplanned or emergency hospital admission if they are directly implicated in the aetiology of the patient’s acute deterioration, as the treatment withdrawal may provoke deterioration in behavioural or cognitive symptoms. Antipsychotic medication Antipsychotic medication should be prescribed for severe non-cognitive symptoms (psychosis and/or agitated behaviour causing significant distress) only if there is severe distress or an immediate risk of harm to the person with dementia or others. The treatment should be commenced only if • Risks and benefits have been fully discussed; assess cerebrovascular risk factors and discuss possible increased risk of stroke/transient ischaemic attack and possible adverse effects on cognition • Changes in cognition are regularly assessed and recorded; consider alternative medication if necessary • Target symptoms have been identified, quantified and documented, and changes are regularly assessed and recorded • Co morbid conditions, such as depression, have been considered • The drug dose is started low and titrated upwards • Treatment is time limited and regularly reviewed (every 3 months or according to clinical need). SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 14/20
  15. 15. Treatment with haloperidol, pimozide, and ziprasidone is contraindicated in the following circumstances (Neuroleptics and Cardiac Side Effects IMB publication) • Clinically significant cardiac disorders (e.g. recent acute myocardial infarction, uncompensated heart failure, arrhythmias treated with class IA and III antiarrhythmic medicinal products) • QTc interval prolongation on ECG • History of ventricular arrhythmia or Torsades de pointes, • Uncorrected hypokalaemia • Patients taking other QT prolonging drugs. These substances should be used with caution in patients with cardiovascular disease or a family history of QT prolongation. It is recommended that patients undergo a baseline ECG prior to commencement of treatment and that the need for on- going ECG monitoring is assessed on an individual patient basis. Whilst on therapy, the dose of neuroleptic should be reduced if the QT is prolonged and should be discontinued if QTc is > 500ms. Periodic electrolyte monitoring is recommended during therapy and the concomitant use of other neuroleptic medicines should be avoided. In DLB, monitor particularly for neuroleptic sensitivity reactions (development or worsening of extra pyramidal features or acute, severe physical deterioration). Neuroleptic malignant syndrome (NMS) can develop in 0.1% to 2.5% of all patients treated with neuroleptics (Kornhuber 1994). Mortality in NMS ranges from 2.0% to 16% with different treatment modalities (Reulbach 2007). Future de novo therapies Trials are currently underway for possible future therapies in treatment and prevention of Alzheimer's disease especially in the field of immunotherapy and vaccines. A common target is the beta-amyloid protein for which antibodies and vaccines are being tested. Etanercept, an anti-tumour necrosis factor alpha protein is also being studied as a possible de novo therapy. Results from these trials are awaited. Useful information sources/websites Organisation Contact details St. Vincent’s University Hospital, Dept of Geriatric Medicine Ms. Lorraine Murray, Senior Administrator T: 01- 2094549 F: 01-2094609 St. Vincent’s University Hospital Carew House Day Hospital T: 01- 2094122 F: 01-2094026 The Alzheimer Society of Ireland T: 1800 341341 SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 15/20
  16. 16. The Carer's Association T: 057-9322920 Dementia Services Information & Development Centre T: 01-4162035 Fax: 01-4163482 The Mercer's Institute for Research on Ageing Transport and Mobility Consultants Ireland Mr. Tony Regan Tel: 0404-43854 email: SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 16/20
  17. 17. References Bedard M, Molloy M, Lever J. (1996). Should demented patients drive alone? Journal of the American Geriatrics Society. 44, S9. Birks J. Cholinesterase Inhibitors for A;zheimer's Disease. Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD005593. DOI: 10.1002/14651858.CD005593. Boustani M, MD, MPH; Britt Peterson, MD, MPH; Laura Hanson, MD, MPH; Russell Harris, MD, MPH; and Kathleen N. Lohr, PhD Screening for Dementia in Primary Care: A Summary of the Evidence for the U.S. Preventive Services Task Force Ann Intern Med. 2003;138:927-937. Brodaty H, Moore CM. The Clock Drawing Test for dementia of the Alzheimer's type: A comparison of three scoring methods in a memory disorders clinic. Int J Geriatr Psychiatry. 1997 Jun;12(6):619-27 Dougall, N.J., Bruggink, S. & Ebmeier, K.P. (2004) Systematic review of the diagnostic accuracy of 99mTc-HMPAO- SPECT in dementia. American Journal of Geriatric Psychiatry, 12, 554–570. Drachmann DA, Sweaver JM. (1993) Driving and Alzheimer's disease: the risk of crashes. Neurology, 43, 2448-56 Francis J, Kapoor WM. Prognosis after hospital discharge of older medical patients with delirium. Journal of the American Geriatrics Society 1992 40;601-6 Gifford, D.R., Holloway, R.G. & Vickrey, B.G. (2000) Systematic review of clinical prediction rules for neuroimaging in the evaluation of dementia. Archives of Internal Medicine, 160, 2855–2862. Gold, G., Bouras, C., Canuto, A., et al. (2002) Clinicopathological validation study of four sets of clinical criteria for vascular dementia. The American Journal of Psychiatry, 159, 82–87. Hofman, A., Ott, A., Breteler, M.M., et al. (1997) Atherosclerosis, apolipoprotein E and prevalence of dementia and Alzheimer’s disease in the Rotterdam Study. The Lancet, 349, 151–154. Hsich, G., Kenney, K., Gibbs, C.J, et al. (1996) The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. New England Journal of Medicine, 335, 924–930. Jayadev S, Steinbart EJ, Chi YY, Kukull WA, Schellenberg GD, Bird TD. Conjugal Alzheimer disease: risk in children when both parents have Alzheimer disease. Arch Neurol. 2008 Mar;65(3):373-8. SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 17/20
  18. 18. Knopman, D.S., DeKosky, S.T., Cummings, J.L., et al. (2001) Practice parameter: diagnosis of dementia (an evidence- based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56, 1143–1153. Kornhuber J, Weller M: Neuroleptic malignant syndrome. Curr Opin Neurol 1994, 7:353-357. Lai F, Williams RS. Arch Neurol. 1989 Aug;46(8):849-53. A prospective study of Alzheimer disease in Down syndrome. Litvan, I., Bhatia, K.P., Burn, D.J., et al. (2003) Movement Disorders Society Scientific Issues Committee report: SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Movement Disorders, 18, 467–486. Lobo, A., Launer, L.J., Fratiglioni, L., et al. (2000) Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology, 54, S4–S9. Maidment I, Fox C, Boustani M. Cholinesterase inhibitors for Parkinson’s disease dementia. Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD004747. DOI: 10.1002/14651858.CD004747.pub2. McKeith, I.G., Ballard, C.G., Perry, R.H., et al. (2000) Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies. Neurology, 54, 1050–1058 McKeith, I.G., Dickson, D.W., Lowe, J., et al. (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology, 65, 1863–1872. McKeith, I.G., Galasko, D., Kosaka, K., et al. (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology, 47, 1113–1124. McKhann, G., Drachman, D., Folstein, M., et al. (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS- ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology, 34, 939–944. McKhann, G.M., Albert, M.S., Grossman, M., et al. (2001) Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick’s Disease. Archives of Neurology, 58, 1803–1809. McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003154. DOI: 10.1002/14651858.CD003154.pub5. Mioshi E, Dawson K, Mitchell J, Arnold R, Hodges JR. Int J Geriatr Psychiatry. 2006 Nov;21(11):1078-85. The Addenbrooke's Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening. Moroney, J.T., Meta-analysis of the Hachinski Ischaemic Score in pathologically verified dementias. Neurology, 49, 1096 – 1105. SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 18/20
  19. 19. Mosconi, L. (2005) Brain glucose metabolism in the early and specific diagnosis of Alzheimer’s disease. FDG-PET studies in MCI and AD. European Journal of Nuclear Medicine and Molecular Imaging, 32, 486–510. Neary, D., Snowden, J.S., Gustafson, L., et al. (1998) Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology, 51, 1546–1554. Neuroleptics and Cardiac Side Effects. Irish Medicines Board Notice Information:Human Medicines Publication-31st May 2007 O’Brien, J.T., Colloby, S., Fenwick, J., et al. (2004) Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis of dementia with Lewy bodies. Archives of Neurology, 61, 919–925. O'Neill D. (1992) Physicians, elderly drivers and dementia. Lancet 1992 339, 41-3. O'Neill D. Driving and Mobility. Oxford textbook of Geriatric Medicine 2nd Edition. 1157-1164. Peters, R., Peters, J., Warner, J., Beckett, N., Bulpitt, C. (2008) Alcohol, dementia and cognitive decline in the elderly: a systematic review. Age and Ageing 2008; 37:505-12. Reulbach U, Dütsch C, Biermann T, Sperling W, Thuerauf N, Kornhuber J, Bleich S. Managing an effective treatment for neuroleptic malignant syndrome. Crit Care. 2007;11(1):R4. Rocca, W.A., Hofman, A., Brayne, C., et al. (1991) Frequency and distribution of Alzheimer’s disease in Europe: a collaborative study of 1980–1990 prevalence findings. The EURODEM-Prevalence Research Group. Annals of Neurology, 30, 381–390. Roman, G.C., Tatemichi, T.K., Erkinjuntti, T., et al. (1993) Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN international Workshop. Neurology, 43, 250–260. Saunders, P.A., Copeland, J.R., Dewey, M.E., et al. (1991) Heavy drinking as a risk factor for depression and dementia in elderly men. Findings from the Liverpool longitudinal community study. The British Journal of Psychiatry, 159, 213–216. Strittmatter, W.J., Saunders, A.M., Schmechel, D., et al. (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America, 90, 1977–1981. Trobe JD, Waller PF, Cook-Flannagan CA, Teshima SM, Bieliuskas LA (1996) Crashes and violations among drivers with Alzheimer's disease. Archives of Neurology, 53, 411-16. SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 19/20
  20. 20. Valenzuela, M.J. & Sachdev, P. (2005) Brain reserve and dementia: a systematic review. Psychological Medicine, 35, 1– 14. Verghese, J., Lipton, R.B., Katz, M.J., et al. (2003) Leisure activities and the risk of dementia in the elderly. The New England Journal of Medicine, 348, 2508–2516. White, N., Scott, A., Woods, R.T., et al. (2002) The limited utility of the mini mental state examination in screening people over the age of 75 years for dementia in primary care. The British Journal of General Practice, 52, 1002–1003. Wilson, R.S., Mendes De Leon, C.F., Barnes, L.L., et al. (2002) Participation in cognitively stimulating activities and risk of incident Alzheimer disease. The Journal of the American Medical Association, 287, 742–748. SVUH_MedEl_DementiaReferencedoc_DraftGH2_2008 20/20