Clinical Evidence Handbook

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Dementia

 


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Am Fam Physician. 2014 Jan 15;89(2):117-118.

Author disclosure: Rob Butler and Raghavakurup Radhakrishnan declare that they have no competing interests.

Dementia is characterized by chronic, global, nonreversible deterioration in memory, executive function, and personality. Speech and motor function may also be impaired in persons with dementia.

Median life expectancy for persons with Alzheimer disease and Lewy body dementia is about six years after diagnosis, although many persons with these conditions may live much longer.

Randomized controlled trials of dementia are often not representative of all persons with dementia; most trials are of six months' duration or less, are not in primary care, and are in persons with Alzheimer disease. Few randomized controlled trials address vascular dementia, and fewer still address Lewy body dementia.

Some cognitive symptoms of dementia may be improved with acetylcholinesterase inhibitors such as donepezil, galantamine, and rivastigmine.

  • Acetylcholinesterase inhibitors may improve cognitive function and global function scores compared with placebo at 12 to 26 weeks in persons with Alzheimer disease. However, they may be associated with an increase in adverse effects, particularly gastrointestinal symptoms (anorexia, nausea, vomiting, or diarrhea).

We do not know whether cognitive stimulation, music therapy, reminiscence therapy, omega-3 fatty acids (fish oil), statins, or nonsteroidal anti-inflammatory drugs are effective at improving cognitive outcomes in persons with cognitive symptoms from dementia, because we found insufficient evidence.

In persons with cognitive symptoms, memantine may modestly improve cognitive function and global function scores in persons with Alzheimer disease over 24 to 28 weeks, and may modestly improve activities of daily living scores in persons with moderate to severe Alzheimer disease.

  • Although memantine is associated with a statistically significant increase in cognition scores in some population groups, the clinical importance of some of these results is unclear.

We found inconsistent evidence on the effects of Ginkgo biloba on cognitive outcomes, which varied by the analysis performed.

  • We found no evidence that Ginkgo biloba improves activities of daily living outcomes, but the available evidence was weak.

Acetylcholinesterase inhibitors may marginally improve neuropsychiatric symptoms compared with placebo in persons with behavioral and psychological symptoms of dementia, but they are also associated with adverse effects.

  • We do not know whether antidepressants (clomipramine, fluoxetine, imipramine, or sertraline) improve depressive symptoms in persons with Alzheimer disease that is associated with depression.

Many randomized controlled trials were small and short-term, and adverse effects were sparsely reported.

Memantine may be associated with a small improvement in neuropsychiatric symptoms compared with placebo in persons with behavioral and psychological symptoms of dementia, but it is also associated with adverse effects.

We do not know whether diazepam, lorazepam, aromatherapy, cognitive behavior therapy, exercise, carbamazepine, or sodium valproate/valproic acid is effective at improving neuropsychiatric symptoms in persons with behavioral and psychological symptoms of dementia, because we found insufficient evidence.

Some antipsychotics may improve neuropsychiatric symptoms or aggression in persons with behavioral and psychological symptoms of dementia, but antipsychotics are also associated with an increased risk of severe adverse events such as stroke, transient ischemic attack, or death.

Caution: Regulatory bodies have issued alerts that conventional and atypical antipsychotics are associated with an increased risk of death in older persons treated for dementia-related psychosis.

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Clinical Questions

What are the effects of treatments on cognitive symptoms of dementia (Alzheimer disease, Lewy body dementia, or vascular dementia)?

Likely to be beneficial

Acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine)

Memantine (evidence of statistical benefit, but results of unclear clinical importance)

Unknown effectiveness

Ginkgo biloba

Nonsteroidal anti-inflammatory drugs

Nonpharmacologic interventions (cognitive stimulation, music therapy, reminiscence)

Omega-3 fatty acids (fish oil)

Statins

What are the effects of treatments on behavioral and psychological symptoms of dementia (Alzheimer disease, Lewy body dementia, or vascular dementia)?

Likely to be beneficial

Acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine; evidence of marginal benefit)

Memantine (evidence of marginal benefit)

Trade-off between benefits and harms

Antipsychotic medications (limited evidence of effectiveness; however, associated with severe adverse effects, including cerebrovascular events and death)

Unknown effectiveness

Antidepressants (clomipramine, fluoxetine, imipramine, sertraline) in persons with depression and dementia

Benzodiazepines (diazepam, lorazepam)

Mood stabilizers (carbamazepine, sodium valproate/valproic acid)

Nonpharmacologic interventions (aromatherapy, cognitive behavior therapy, exercise)

Clinical Questions

What are the effects of treatments on cognitive symptoms of dementia (Alzheimer disease, Lewy body dementia, or vascular dementia)?

Likely to be beneficial

Acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine)

Memantine (evidence of statistical benefit, but results of unclear clinical importance)

Unknown effectiveness

Ginkgo biloba

Nonsteroidal anti-inflammatory drugs

Nonpharmacologic interventions (cognitive stimulation, music therapy, reminiscence)

Omega-3 fatty acids (fish oil)

Statins

What are the effects of treatments on behavioral and psychological symptoms of dementia (Alzheimer disease, Lewy body dementia, or vascular dementia)?

Likely to be beneficial

Acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine; evidence of marginal benefit)

Memantine (evidence of marginal benefit)

Trade-off between benefits and harms

Antipsychotic medications (limited evidence of effectiveness; however, associated with severe adverse effects, including cerebrovascular events and death)

Unknown effectiveness

Antidepressants (clomipramine, fluoxetine, imipramine, sertraline) in persons with depression and dementia

Benzodiazepines (diazepam, lorazepam)

Mood stabilizers (carbamazepine, sodium valproate/valproic acid)

Nonpharmacologic interventions (aromatherapy, cognitive behavior therapy, exercise)

Definition

Dementia is characterized by memory loss (initially of recent events), loss of executive function (such as the ability to make decisions or sequence complex tasks), other cognitive deficits, and changes in personality. This decline must be serious enough to affect social or occupational functioning, and reasonable attempts must be made to exclude other common conditions, such as depression and delirium.

Alzheimer disease is a type of dementia characterized by an insidious onset and slow deterioration, and involves impairments in memory, speech, personality, and executive function. It should be diagnosed after other systemic, psychiatric, and neurologic causes of dementia have been excluded clinically and by laboratory investigation.

Vascular dementia is often caused by multiple large or small vessel disease. It often presents with a stepwise deterioration in cognitive function, with or without language and motor dysfunction. It usually occurs in the presence of vascular risk factors (diabetes mellitus, hypertension, arteriosclerosis, and smoking). Characteristically, it has a more sudden onset and stepwise progression than Alzheimer disease, and often has a patchy picture of cognitive deficits.

Lewy body dementia is a type of dementia that involves insidious impairment of cognitive function with parkinsonism, visual hallucinations, and fluctuating cognitive abilities. Nighttime disturbance is common, and there is an increased risk of falls.

Careful clinical examination of persons with mild to moderate dementia and the use of established diagnostic criteria accurately identify 70% to 90% of causes confirmed postmortem. In all types of dementia, individuals will experience problems with cognitive functioning and are likely to experience behavioral and psychological symptoms of dementia. Where possible, we have divided outcomes into cognitive or behavioral/psychological, although there is often considerable crossover between these outcomes, both clinically and in research. This review deals solely with persons who have Alzheimer disease, Lewy body dementia, or vascular dementia.

Incidence and Prevalence

About 6% of persons older than 65 years and 30% of persons older than 90 years have some form of dementia. Dementia is rare before 60 years of age. Alzheimer disease and vascular dementia (including mixed dementia) are each estimated to account for 35% to 50% of dementia, and Lewy body dementia is estimated to account for up to 5% of dementia in older persons, varying with geographic, cultural, and racial factors. There are numerous other causes of dementia, all relatively rare, including frontotemporal dementia, alcohol-related dementia, Huntington disease, normal-pressure hydrocephalus, human immunodeficiency virus infection, syphilis, subdural hematoma, and some cerebral tumors.

Etiology and Risk Factors

The cause of Alzheimer disease is unclear. A key pathologicprocess is deposition of abnormal amyloid in thecentral nervous system. Another early change is abnormalphosphorylation of tau, an intracellular structuralprotein. This results in apoptosis and neurofibrillarytangles. Disease-modifying agents in development targetboth processes. Most individuals with the relatively rarecondition of early-onset Alzheimer disease (before 60years of age) exhibit an autosomal dominant inheritancedue to mutations in presenilin or amyloid precursorprotein genes. Several gene mutations (on the amyloidprecursor protein, presenilin 1, and presenilin 2 genes)have been identified. Later-onset dementia is sometimesclustered in families, but specific gene mutations havenot been identified. Down syndrome, cardiovascularrisks, and lower premorbid intellect may be risk factorsfor Alzheimer disease. Alzheimer disease and vascularpathology often coexist.

Vascular dementia is related to cardiovascular riskfactors, such as smoking, arteriosclerosis, hypertension,and diabetes. Lewy body dementia is characterized bythe presence of Lewy bodies (abnormal intracellularinclusions consisting of α-synuclein) in the cortex.Brain acetylcholine activity is reduced in many formsof dementia, and the level of reduction correlates with cognitive impairment.

Prognosis

Alzheimer disease usually has an insidious onset withprogressive reduction in cerebral function. Diagnosis isdifficult in the early stages. Median life expectancy afterdiagnosis is about six years, although many persons withAlzheimer disease live much longer. We found no reliabledata on prognosis for vascular dementia. Personswith Lewy body dementia have an average life expectancyof about six years after diagnosis. Behavioral problems,depression, and psychotic symptoms are common in alltypes of dementia. Eventually, most persons with dementiahave difficulty doing simple tasks without help.

Author disclosure: Rob Butler and Raghavakurup Radhakrishnan declare that they have no competing interests.

This is one in a series of chapters excerpted from the Clinical Evidence Handbook, published by the BMJ Publishing Group, London, U.K. The medical information contained herein is the most accurate available at the date of publication. More updated and comprehensive information on this topic may be available in future print editions of the Clinical Evidence Handbook, as well as online at http://www.clinicalevidence.bmj.com (subscription required).

A collection of Clinical Evidence Handbook published in AFP is available at http://www.aafp.org/afp/bmj.



 

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