Dementia

Dementia is "progressive decline in two or more cognitive domains that is severe enough to interfere with the performance of everyday activities."

Deficits in cognitive function contribute to impaired functional status. The deficits in the domains of cognitive function are:

• Agnosia - "Failure to recognize or identify objects despite intact sensory function"
• Aphasia - "Deterioration of language function"
• Apraxia - "Impaired ability to execute motor activities despite intact motor abilities, sensory function, and comprehension of the required task"
• Disturbance in executive functioning - "The ability to think abstractly and to plan, initiate, sequence, monitor, and stop complex behavior"

Classification

Vascular dementia can affect both cortical and subcortial locations.

Cortical dementias

Among the many causes of cortical dementia, common causes are:

• Alzheimer's disease which usually affects posterior cortical regions before progressing to the frontal cortex.
• Frontotemporal lobar degeneration (Pick's Disease)
• Dementia with Lewy bodies

Subcortical dementias

Among the many causes of subcortical dementia, common causes are:

• Parkinson's disease
• Vitamin B12 deficiency
• Some vascular dementias

Epidemiology

22.2% of individuals in the United States age 71 years or older have cognitive impairment without dementia (Dementia Severity Rating Scale score of 6 to 11). 12% of these patients progress to dementia annually. Progression is more common among patients with subtypes of prodromal Alzheimer disease and cerebrovascular disease.

Risk factors

Repeated episodes of hypoglycemia are associated with dementia.

Hypoxia from sleep disordered breathing such as sleep apnea may increase risk.

Diagnosis

Studies on diagnosing dementia are compromised by the lack of a true reference standard for comparison.

A number of systematic reviews, including ones by the U.S. Preventive Services Task Force (USPSTF), Rational Clinical Examination, and others, have summarized the diagnostic accuracy of screening tests.

The single best finding may be disoriented to year.

Ascertainment of decision making capacity

Decision making can be assessed with the Aid to Capacity Evaluation (ACE).

Consequences of labeling

In one study, learning of having mild cognitive impairment reduced stress.

Investigation of causes

Among rapidly progressive cases, causes include:

• Sporadic Creutzfeldt-Jakob disease (sCJD)
• Immunological (vasculitis, encephalomyelitis, and limbic encephalitis)
• Neoplastic (mainly lymphoma)
• Infectious (fungal, viral, and parasitic)
• Metabolic (including Wernicke encephalopathy)

Temporal disorientation

Among hospitalized geriatric patients, "failure to identify either year or month correctly was 95% sensitive and 86.5% specific for the detection of cognitive impairment".

Sweet 16

The Sweet 16 is available online at http://hospitalelderlifeprogram.org/private/sweet16-disclaimer.php?pageid=01.09.00. Accuracy using a score of less than 14:

• sensitivity 99%
• specificity 72%

Mini-mental state examination

The Mini-mental state examination (MMSE) is the most studied test. A systematic review concluded that the accuracy of the MMSE is::

• sensitivity 71% to 92%
• specificity 56% to 96%

Copies of ther MMSE can be purchased (http://www4.parinc.com/Products/Product.aspx?ProductID=MMSE). A copy of the Mini-mental state examination can be found in the appendix of the original publication.

Modified Mini-Mental State examination (3MS)

A meta-analysis concluded that the Modified Mini-Mental State (3MS) examination has:

• sensitivity 83% to 94%
• specificity 85% to 90%

A copy of the 3MS is online.

Abbreviated mental test score

A meta-analysis concluded:

sensitivity 73% to 100%

specificity 71% to 100%

Clinical Dementia Rating

The Clinical Dementia Rating scale can quantify severity of functional impairment.

Clock drawing task

Dementia type	CLOX1 (Executive control)	CLOX2 (Posterior cortical)	Pentagons copying on MMSE	Total MMSE score
Posterior cortical and diffuse cortical dementias	Abnormal	Abnormal	Abnormal	Abnormal
Subcortical and frontal cortical dementias	Abnormal	Normal	Normal	Normal

The Clock drawing task (CLOX) consists of two tests and is available online at PubMed Central. The CLOX1 task has the subject draw a clock face without any prompting other than the instructions "Draw me a clock that says 1:45. Set the hands and numbers on the face so that a child could read them". The CLOX1 is tests executive function and correlates with the EXIT25 test of executive function. The CLOX2 task has the subject copy a clock face from an example, does not test executive function and correlates with the MMSE.

The CLOX may avoid the bias of the MMSE toward cortical dementias. In addition, "as Alzheimer’s disease affects posterior cortical regions before invading the frontal cortex, isolated ECF impairment (CLOX1) is not likely to represent early Alzheimer’s disease." Thus, isolated abnormalities of the CLOX1 may be able to detect reversible dementias such as subcortical stroke, depression, vitamin B12 deficiency, polypharmacy, and hypothyroidism.

Other examinations

Many other tests have been studied including the Executive Interview (EXIT).

Laboratory tests

Apolipoprotein E4

Although apolipoprotein E4 is an important susceptibility gene for Alzheimer's disease, its sensitivity and specificity are insufficient (65 and 68 percent, respectively) to be used as a diagnostic test.

Apolipoprotein E4 does not added to other tests in predicting who will develop Alzheimer's.

Treatment

Approaches to treatment

"Actively involving caregivers in making choices about treatments" my be the most important way to delay institutionalization of patients with dementia.

The use of care managers may help.

Non drug treatments

Behavior management techniques (BMT)

Behavior management techniques (BMT) might help. More specifically, " interventions that address behavioral issues and unmet needs" may help.

Exercise

Home-based program of physical activity might benefit according to a randomized controlled trial.

Bright lights

Any initial randomized controlled trial suggests that bright light helps.

Medications

According to the clinical practice guideline by the American College of Physicians, "the evidence is insufficient to compare the effectiveness of different pharmacologic agents for the treatment of dementia."

"Treatment of dementia with cholinesterase inhibitors and memantine can result in statistically significant but clinically marginal improvement in measures of cognition and global assessment of dementia" according to a systematic review for the clinical practice guideline.

Cholinesterase inhibitors

Available cholinesterase inhibitors drugs are donepezil, galantamine, rivastigmine, and tacrine.

Neuropeptide-modifier

Memantine is a neuropeptide-modifier that acts on the N-Methyl-D-Aspartate (NMDA) cell surface receptors for the neurotransmitter glutamate.

Anti-psychotics

The newer, atypical antipsychotic agents (olanzapine, quetiapine, risperidone), were found to have "adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease." A more recent randomized controlled trial that compared the second generation anti-psychotic agents found that none improved functioning, care needs, or quality of life with statistical significance; however, olanzapine and risperidone may reduce anger. Regardless, antipsychotic agents may increase mortality.

Withdrawing psychotropics agents may prevent accidental falls.

Melatonin

Melatonin mayor may not help with associated sleep and behavior disturbance.

Dietary supplements

Ginkgo biloba has conflicting evidence regarding its efficacy.

Randomized controlled trials of B vitamins

Trial	Patients	Intervention	Comparison	Outcome	Results		Comment
					Intervention	Control
Aisen 2008	• Mild to moderate Alzheimers disease • Normal folic acid, vitamin B12, and homocysteine levels	• 5 mg/d of folate • 25 mg/d of vitamin B6 • 1 mg/d of vitamin B12	Placebo				negative study
Durga 2007	50-70 years old • raised plasma homocysteine • normal serum vitamin B12	800 microg/d folate	Placebo				positive study
McMahon 2006	≥ 65 years old • raised plasma homocysteine	• 1000 microg/d folate • 500 microg/d of Vitamin B12 • 10 mg/d of vitamin B6	Placebo	Tests of cognition			negative study

Analgesics

Treating pain may reduce agitation.

Prevention

Physical activity

Most, but not all studies find that physical activity is associated with reduced risk of dementia. These observational studies cannot prove cause and effect.

Mental activity

Maintaining activities such as cognitive games and reading, playing musical instruments, and physical activities are associated with reduced the risk of dementia in an observational study.

Medications

Various medications have been associated with progression or prevention (cholinesterase inhibitors, N-methyl-D-aspartate receptor antagonists, renin-angiotensin system blockers, and hydroxymethylglutaryl-coenzyme A reductase inhibitors) of dementia.

Observational, non-ramdomized cohort studies suggest that hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) may or may not prevent dementia.

Supplements

Ginkgo biloba does not prevent dementia according to a large randomized controlled trial and systematic review by the Cochrane Collaboration in spite of earlier studies that were positive.

Screening

Practice guidelines

In 2003, a clinical practice guideline by the U.S. Preventive Services Task Force (USPSTF) gave a grade I recommendation, indicating "the evidence is insufficient to recommend for or against routine screening for dementia in older adults".

Evidence

The late-life dementia risk index:

late-life dementia risk index

Risk	Score	Incidence of dementia within 6 years
High	≥8	56%
Intermediate	4-7	23%
Low	0-3	4%
Based on Table 3 from Barnes et al.

• older age (1–2 points)
• poor cognitive test performance (2–4 points)
• body mass index <18.5 (2 points)
• ≥1 apolipoprotein E 4 alleles (1 point)
• cerebral MRI findings of white matter disease (1 point)
• cerebral ventricular enlargement (1 point)
• internal carotid artery thickening on ultrasonography (1 point)
• history of coronary artery bypass surgery (1 point)
• slow physical performance (1 point)
• lack of alcohol consumption (1 point)

Prognosis

Functional Assessment Staging (FAST) scale Stage 6 6a = inability to dress 6b = inability to bathe 6c = inability to toilet 6d = urinary incontinence at least occasionally 6e = bowel incontinence at least occasionally Stage 7 7a = speech is limited to less than 5 words 7b = all intelligible vocabulary is lost 7c = nonambulatory 7d = unable to sit independently 7e = unable to smile 7f = unable to hold head up

Mild cognitive impairment

Mortality is increased with mild cognitive impairment. A systematic review of cohort studies concluded that the rate conversion of mild cognitive impairment to dementia is about 4% per year."

Once a patient has advanced dementia, defined as a score of 5 or 6 on the Cognitive Performance Scale from the most recent Minimum Data Set assessment (a score of 5 corresponds to a score of 5.1 (95% CI: ±10) on the Folstein Mini–Mental State Examination, the median survival is about 18 months.

Dementia

Mortality can also be predicted by Medicare guidelines for use of Hospice. If the patients is a stage 7c on the Functional Assessment Staging (FAST) scale and has had a prior complication of dementia such aspiration pneumonia, stage 4 or more pressure ulcer, upper urinary tract infection, or inability to eat, then mortality is predicted at 6 months with accuracy of:

• Sensitivity 20%
• Specificity 89%

Similarly, mortality can be predicted by the ADEPT score.