BACKGROUND: Effects of drug treatment of clinical Alzheimer-type dementia (CATD) are uncertain.
PURPOSE: To summarize evidence on the effects of prescription drugs and supplements for CATD treatment.
DATA SOURCES: Electronic bibliographic databases (inception to November 2019), ClinicalTrials.gov (to November 2019), and systematic review bibliographies.
STUDY SELECTION: English-language trials of prescription drug and supplement treatment in older adults with CATD that report cognition, function, global measures, behavioral and psychological symptoms of dementia (BPSD), or harms. Minimum treatment was 24 weeks (≥2 weeks for selected BPSD).
DATA EXTRACTION: Studies with low or medium risk of bias (ROB) were analyzed. Two reviewers rated ROB. One reviewer extracted data; another verified extraction accuracy.
DATA SYNTHESIS: Fifty-five studies reporting non-BPSD outcomes (most ≤26 weeks) and 12 reporting BPSD (most ≤12 weeks) were analyzed. Across CATD severity, mostly low-strength evidence suggested that, compared with placebo, cholinesterase inhibitors produced small average improvements in cognition (median standardized mean difference [SMD], 0.30 [range, 0.24 to 0.52]), no difference to small improvement in function (median SMD, 0.19 [range, -0.10 to 0.22]), no difference in the likelihood of at least moderate improvement in global clinical impression (median absolute risk difference, 4% [range, 2% to 4%]), and increased withdrawals due to adverse events. In adults with moderate to severe CATD receiving cholinesterase inhibitors, low- to insufficient-strength evidence suggested that, compared with placebo, add-on memantine inconsistently improved cognition and improved global clinical impression but not function. Evidence was mostly insufficient about prescription drugs for BPSD and about supplements for all outcomes.
LIMITATION: Most drugs had few trials without high ROB, especially for supplements, active drug comparisons, BPSD, and longer trials.
CONCLUSION: Cholinesterase inhibitors and memantine slightly reduced short-term cognitive decline, and cholinesterase inhibitors slightly reduced reported functional decline, but differences versus placebo were of uncertain clinical importance. Evidence was mostly insufficient on drug treatment of BPSD and on supplements for all outcomes.
PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).
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.
CONCLUSIONS: 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.
El deterioro neurocognitivo debido a la enfermedad de Alzheimer (anteriormente denominado demencia de Alzheimer) (AD) es la forma más común de deterioro cognitivo en todo el mundo. Dado el aumento previsto de la población de 65 años o más, se prevé que la prevalencia de personas con EA aumentará exponencialmente durante los próximos 30 años. Los síntomas neuropsiquiátricos no cognitivos (SNP) ocurren comúnmente en la EA y se asocian con resultados adversos para los pacientes y sus cuidadores. Esta revisión resume ensayos controlados aleatorios (ECA) publicados entre 2004 y 2014 con una medida de resultado primaria de cambio en la gravedad de los síntomas para NPS en la EA. De los 388 artículos identificados inicialmente mediante una búsqueda bibliográfica, 33 ensayos cumplieron los criterios de inclusión. Quince de estos estudios tenían agitación / agresión como un síntoma objetivo. Veintiocho evaluaron tratamientos farmacológicos, incluyendo psicotrópicos, potenciadores cognitivos, estimulantes y nutracéuticos. Las intervenciones no farmacológicas incluyeron luz brillante, música, ejercicio y terapias de estimulación cognitiva. Entre las intervenciones farmacológicas, la eficacia modesta se informó con aripiprazol, citalopram, trazodona, metilfenidato, y analgésicos programados. Se observó una reducción significativa en la gravedad de los síntomas con casi todas las intervenciones no farmacológicas. Las variaciones en la metodología como los criterios de inclusión, el establecimiento del estudio y las medidas de resultado limitan la generalización de estos resultados. Las barreras a la implementación de intervenciones no farmacológicas en entornos clínicos incluyen limitaciones de recursos y capacitación. La terapia electroconvulsiva y el dronabinol son prometedores como estrategias de tratamiento emergentes. Se necesitan ensayos clínicos aleatorios para validar la utilidad de la terapia electroconvulsiva y el dronabinol, incluyendo dónde y con quién estas intervenciones resultarán más valiosas. (PsycINFO Database Record (c) 2016 APA, todos los derechos reservados)
Effects of drug treatment of clinical Alzheimer-type dementia (CATD) are uncertain.
PURPOSE:
To summarize evidence on the effects of prescription drugs and supplements for CATD treatment.
DATA SOURCES:
Electronic bibliographic databases (inception to November 2019), ClinicalTrials.gov (to November 2019), and systematic review bibliographies.
STUDY SELECTION:
English-language trials of prescription drug and supplement treatment in older adults with CATD that report cognition, function, global measures, behavioral and psychological symptoms of dementia (BPSD), or harms. Minimum treatment was 24 weeks (≥2 weeks for selected BPSD).
DATA EXTRACTION:
Studies with low or medium risk of bias (ROB) were analyzed. Two reviewers rated ROB. One reviewer extracted data; another verified extraction accuracy.
DATA SYNTHESIS:
Fifty-five studies reporting non-BPSD outcomes (most ≤26 weeks) and 12 reporting BPSD (most ≤12 weeks) were analyzed. Across CATD severity, mostly low-strength evidence suggested that, compared with placebo, cholinesterase inhibitors produced small average improvements in cognition (median standardized mean difference [SMD], 0.30 [range, 0.24 to 0.52]), no difference to small improvement in function (median SMD, 0.19 [range, -0.10 to 0.22]), no difference in the likelihood of at least moderate improvement in global clinical impression (median absolute risk difference, 4% [range, 2% to 4%]), and increased withdrawals due to adverse events. In adults with moderate to severe CATD receiving cholinesterase inhibitors, low- to insufficient-strength evidence suggested that, compared with placebo, add-on memantine inconsistently improved cognition and improved global clinical impression but not function. Evidence was mostly insufficient about prescription drugs for BPSD and about supplements for all outcomes.
LIMITATION:
Most drugs had few trials without high ROB, especially for supplements, active drug comparisons, BPSD, and longer trials.
CONCLUSION:
Cholinesterase inhibitors and memantine slightly reduced short-term cognitive decline, and cholinesterase inhibitors slightly reduced reported functional decline, but differences versus placebo were of uncertain clinical importance. Evidence was mostly insufficient on drug treatment of BPSD and on supplements for all outcomes.
