Diagnosis and Treatment of Clinical Alzheimer’s-Type Dementia

A review of the evidence regarding cognitive screening tests used to “diagnose” (identify patients with cognitive impairment that could be Alzheimer’s Disease) and the (lack of) effectiveness of currently available medications use to treat it. James W. Mold, MD, MPH

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Objective. To summarize evidence on: (1) the accuracy of brief cognitive tests for identifying clinical Alzheimer’s-type dementia (CATD) in individuals with suspected cognitive impairment; (2) the accuracy of biomarkers for identifying Alzheimer’s disease (AD) in individuals with dementia; and (3) the benefits and harms of prescription drugs and supplements for cognition, function, and behavioral and psychological symptoms of dementia (BPSD) in patients with CATD.

Data sources. Electronic bibliographic databases to March 2019, ClinicalTrials.gov, systematic review bibliographies.

Review methods. Cognitive test accuracy studies must have used explicit CATD diagnostic criteria and a non-CATD control group. Biomarker accuracy studies must have used neuropathologic criteria to define AD cases and non-AD controls. All treatment trials must have enrolled participants with CATD; those evaluating BPSD enrolled individuals with CATD and BPSD. Minimum trial duration was 2 weeks for agitation, aggression, psychosis, and disinhibited sexual behavior, and 24 weeks for other outcomes. Two reviewers rated risk of bias (ROB) and strength of evidence. One reviewer extracted data; a second checked accuracy. We analyzed English-language studies with low or medium ROB.

Results. We analyzed 56 unique studies on the accuracy of brief cognitive tests for CATD, 24 on accuracy of biomarkers for AD (15 brain imaging, nine cerebrospinal fluid [CSF] testing), and 67 trials of CATD treatment (54 reporting cognition or function, 13 reporting BPSD). Multiple brief cognitive tests were highly sensitive and specific (>0.8) for distinguishing CATD from normal cognition, but less so for distinguishing mild CATD from normal cognition or CATD from mild cognitive impairment (MCI). Based on few studies, compared with clinical evaluation alone, amyloid positron emission tomography (PET), fluorodeoxyglucose (FDG)-PET, and combinations of CSF tests added to clinical evaluation may improve accuracy for distinguishing AD from non-AD dementia. Regardless of CATD severity, cholinesterase-inhibitors produced small improvements in cognition and function compared with placebo but may increase serious adverse events and withdrawals due to adverse events. For moderate to severe CATD, memantine plus a cholinesterase inhibitor slightly improved global change and inconsistently improved cognition, but not function, compared with a cholinesterase inhibitor alone. Evidence was mostly insufficient about the effects of prescription drugs and supplements on agitation, aggression, psychosis, or disinhibited sexual behavior.

Conclusion. Brief cognitive tests accurately distinguished CATD from normal cognition, but were less accurate distinguishing smaller clinical differences. Whether biomarkers improve diagnostic accuracy when added to clinical evaluation needs further verification, but potential benefits of testing are limited by lack of effective treatments for AD and non-AD dementias. Cholinesterase-inhibitors slightly outperformed placebo for cognition and function, but evidence of whether any drug treatments improved BPSD was largely insufficient.

Author/s:

Hemmy, L.S, Fink, H.A., Linskens, E.J., Silverman, P.G., MacDonald, R., McCarten, J.R., Talley, K.M.C., Desai, P.J., Forte, M.L., Miller, M.A., Brasure, M., Nelson, V.A., Taylor, B.C., Ng, W., Ouellette, J.M., Greer, N.L., Sheets, K.M., Wilt, T.J., Butler, M.

Some benefits from donepezil in Alzheimer’s disease

Brian Desmarais — Thu, 20 Jun 2019 12:57:52 +0000

Date Added:

June 20, 2019

Journal/Publication:

British Journal of General Practice

Publication Date:

March 1, 2013

Issue:

Volume:

608

Pages:

150

URL:

Some benefits from donepezil in Alzheimer’s disease

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.3399/bjgp13X664333

Keywords

MeSH

Cholinesterase Inhibitors

Synaptic Transmission

brain

RPR Commentary: This is a summary of the data available to date on the effectiveness of donepezil for treatment of patients with Alzheimer’s Disease. I told patients and their families that if a small improvement in functional abilities would make a huge difference in quality of life (e.g. could remain at home 6 months longer), it is probably worth trying donepezil. Otherwise the expense and side effects are not worth the very small benefit. 5 to 10mg seems to be enough. James W. Mold, MD, MPH

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CLINICAL QUESTION

How effective is exercise-based cardiac rehabilitation on mortality, morbidity, and health-related quality of life (QOL) in patients with coronary heart disease (CHD)?

BOTTOM LINE

Compared to usual care, in medium to longer-term follow-up (≥12 months) exercise-based cardiac rehabilitation was found to be effective in reducing overall and cardiovascular mortality in patients with CHD, and appeared to reduce the risk of hospital admissions in the shorter term (<12 months follow-up). There was no reduction seen in the risk of total myocardial infarction, coronary artery bypass graft, or percutaneous transluminal coronary angioplasty.

Author/s:

McAvoy, B.R.