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Diagnosis and Treatment of Clinical Alzheimer’s-Type Dementia

Systematic Review

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Purpose of Review

To summarize evidence on cognitive test accuracy for clinical Alzheimer’s-type dementia (CATD) in suspected cognitive impairment; biomarker accuracy for Alzheimer’s disease (AD) in dementia; and effects of CATD drug treatment.

Key Messages

  • Many brief cognitive tests were highly (>0.8) sensitive and specific distinguishing CATD from normal cognition, but less from mild cognitive impairment.
  • Amyloid PET and MRI were highly sensitive and specific distinguishing autopsy-confirmed AD from non-AD dementia; FDG-PET was highly sensitive and moderately (>0.5 to <0.8) specific; CSF tests were moderately sensitive and specific. Data were limited on biomarkers added to clinical evaluation.
  • Cholinesterase inhibitors (ChI) were slightly better than placebo for cognition and function, but increased withdrawals due to adverse effects; evidence was insufficient for supplements. In moderate to severe CATD, memantine plus ChI slightly improved cognition versus ChI, but not function.
  • Donepezil and antidepressants appeared similar to placebo for agitation and depression, respectively; for other prescription drugs and all supplements, evidence was insufficient on behavioral and psychological symptoms.

Structured Abstract

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.

Journal Citations

Fink HA, Linskens EJ, MacDonald R, et al. Benefits and Harms of Prescription Drugs and Supplements for Treatment of Clinical Alzheimer-Type Dementia: A Systematic Review and Meta-analysis. Annals of Internal Medicine. 28 April 2020. [Epub ahead of print.]

Fink HA, Linskens EJ, Silverman PC, et al. Accuracy of Biomarker Testing for Neuropathologically Defined Alzheimer Disease in Older Adults With Dementia: A Systematic Review. Annals of Internal Medicine. 28 April 2020. [Epub ahead of print.]

Hemmy LS, Linskens EJ, Silverman PC, et al. Brief Cognitive Tests for Distinguishing Clinical Alzheimer-Type Dementia From Mild Cognitive Impairment or Normal Cognition in Older Adults With Suspected Cognitive Impairment: A Systematic Review. Annals of Internal Medicine. 28 April 2020. [Epub ahead of print.]

Citation

Suggested citation: Fink HA, Hemmy LS, Linskens EJ, Silverman PC, MacDonald R, McCarten JR, Talley KMC, Desai PJ, Forte ML, Miller MA, Brasure M, Nelson VA, Taylor BC, Ng W, Ouellette JM, Greer NL, Sheets KM, Wilt TJ, Butler M. Diagnosis and Treatment of Clinical Alzheimer’s-Type Dementia: A Systematic Review. Comparative Effectiveness Review No. 223. (Prepared by the Minnesota Evidence-based Practice Center under Contract No. 290- 2015-00008-I.) AHRQ Publication No. 20-EHC003. Rockville, MD: Agency for Healthcare Research and Quality; April 2020. Posted final reports are located on the Effective Health Care Program search page. DOI: https://doi.org/10.23970/AHRQEPCCER223.