SynthesisDrugs2026
Use of Sedative-Hypnotic Drugs and the Risk of Developing Alzheimer's Disease: A Systematic Review, Meta-Analysis and Meta-Regression.
Synthesis in Drugs, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
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Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSedative-hypnotics, including benzodiazepines (BZDs) and non-benzodiazepine hypnotics (Z-drugs), are widely prescribed for insomnia and anxiety, particularly in older adults. Their long-term cognitive safety and potential association with Alzheimer's disease (AD) remain uncertain. We examined whether use of BZDs and Z-drugs is associated with incident AD and assessed variation by drug class, pharmacokinetics, and methodological factors.
methodsPubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to 16 August 2025 without language restrictions. Reference lists of eligible articles and reviews were screened. We included observational cohort and nested case-control studies enrolling adults without dementia at baseline that compared BZD or Z-drug users with non-users and reported incident AD diagnosed using validated clinical or administrative criteria (e.g., ICD-9/10, NINCDS-ADRDA, or NIA-AA). We excluded reviews, case reports, conference abstracts, studies with overlapping populations, and studies without extractable effect estimates. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-E. Random-effects meta-analyses were performed separately for odds ratios (ORs) and hazard ratios (HRs). Heterogeneity was quantified with I
resultsThirteen studies (N = 721,354 subjects) were included. Overall sedative-hypnotic use was associated with higher odds of AD (OR 1.29; 95% CI, 1.10-1.53; I
conclusionsUse of BZDs and Z-drugs was associated with increased odds of AD, with variation across drug classes and pharmacokinetic profiles. Short-acting agents, BZDs overall, and Z-drugs were associated with higher risk, whereas broad-acting BZDs were not; this finding should be interpreted with caution given subgroup heterogeneity and limited statistical power. Residual confounding and reverse causation limit causal inference. These results support careful prescribing and the need for prospective studies with detailed characterization of exposure, dose, duration, and clinical indication to clarify whether observed associations reflect drug-related effects or underlying disease processes.
trial registrationPROSPERO protocol number: CRD420251141623.
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