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Dementia: New Data and Practice Guidelines

Results from recent studies examining the neurology of dementia, along with 3 new guidelines, yield insights that may lead to improved clinical care of patients with this devastating illness.

Many clinicians believe that the average patient with Alzheimer's disease (AD) lives about 10 years after diagnosis. However, this estimate is derived from studies that considered survival from time of entry into the study rather than from onset of symptoms, overrepresented patients with more indolent courses, and overlooked patients with rapidly progressive disease who died before study enrollment. In a recent study using data from a large Canadian study of aging, investigators determined at a 5-year follow-up that for 821 patients with AD, possible AD, or vascular dementia, the median adjusted survival time was 3.3 years after onset of symptoms.

Several laboratory measures hold promise for more accurate diagnosis of dementing illnesses. A study of 241 patients (with and without dementia) found that increased levels of tau (a key component of neurofibrillary tangles) and decreased ß-amyloid precursor (Aß42) levels in cerebrospinal fluid are highly predictive of AD, especially in patients with the APOE4 allele ( > 90 percent). Researchers in another study looked at tau mutations in 101 patients with non-Alzheimer dementia (sporadic and familial frontotemporal dementia [FTD]). Incidence of tau mutations was highest in patients with familial FTD (33 percent), suggesting that FTD, similar to AD, has heterogeneous etiologies.

Oxidative stress is increased in AD and other neurologic diseases. Researchers measured 8-hydroxyguanine (8-OHG), a product of oxidative stress on DNA. At autopsy, ratios of 8-OHG to free 8-OHG in ventricular CSF were 108-fold higher in the 18 AD patients than in the 7 controls.

The American Academy of Neurology has published 3 practice guidelines for diagnosing and managing dementia. Guidelines for evaluating patients with mild cognitive impairment (i.e., memory deficits not severe enough to meet dementia criteria) note the increased risk for dementia in patients with mild memory impairment and recommend monitoring with standardized testing (e.g., the Mini-Mental State Examination) and neuropsychologic batteries. Diagnostic guidelines for dementia note that DSM-IIIR criteria (almost identical to DSM-IV) are reliable for AD diagnoses, that only MRI or noncontrast CT is appropriate for screening for dementia, and that patients with new-onset dementia should be screened for depression, B₁₂ deficiency, and hypothyroidism. Dementia management guidelines state that cholinesterase inhibitors provide a small benefit for dementia patients and that vitamin E or selegiline may be useful. Estrogen is not recommended, and data on antioxidants, anti-inflammatory drugs, and anticonvulsants are inconsistent. Behavioral techniques and psychotropic medications (e.g., antipsychotics -- especially atypical ones) -- are useful for agitation, and antidepressants -- especially SSRIs -- for depression (but not agitation). Psychoeducation for families and caregivers may benefit them and delay nursing-home placement.

Comment: The revised mean survival time for dementia is important information for clinicians planning treatment and educating patients and families. The findings regarding tau, Aß42, and 8-OHG raise the hope that future diagnostic tests will help differentiate dementia from psychiatric and other neurological conditions. However, clinical judgment will still be essential in assessing patients with both dementia and primary psychiatric disorders. These studies also hint at components of the pathophysiology of dementia; the 8-OHG finding in particular points to the potential usefulness of therapeutic antioxidant treatment in suspected cases. The 3 practice guidelines provide clear and clinically useful statements about diagnosing and managing dementia that are supported by extensive data.

— G Tucker

Published in Journal Watch Psychiatry June 21, 2001

Citation(s):

Wolfson C et al. A reevaluation of the duration of survival after onset of dementia. N Engl J Med 2001 Apr 12 344 1111-1116.

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Andreasen N et al. Evaluation of CSF-tau and CSF-Aß42 as diagnostic markers for Alzheimer disease in clinical practice. Arch Neurol 2001 Mar 58 373-379.

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Poorkaj P et al. Frequency of tau gene mutations in familial and sporadic cases of non-Alzheimer dementia. Arch Neurol 2001 Mar 58 383-387.

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Lovell MA and Markesbery WR. Ratio of 8-hydroxyguanine in intact DNA to free 8-hydroxyguanine is increased in Alzheimer disease ventricular cerebrospinal fluid. Arch Neurol 2001 Mar 58 392-396.

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Petersen RC et al. Practice parameter: Early detection of dementia: mild cognitive impairment (an evidence-based review). Neurology 2001 May 1 56 1133-1142.

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Knopman D et al. Practice parameter: Diagnosis of dementia (an evidence-based review). Neurology 2001 May 1 56 1143-1153.

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Doody RS. Practice parameter: Management of dementia (an evidence-based review). Neurology 2001 May 1 56 1154-1166.

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