Selective Serotonin Reuptake Inhibitor-Treatment Does Not Show Beneficial Effects on Cognition or Amyloid Burden in Cognitively Impaired and Cognitively Normal Subjects

Bouter, Yvonne; Bouter, Caroline · 2022 · Crossref

DOI: 10.3389/fnagi.2022.883256

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Summary

This study investigates whether selective serotonin reuptake inhibitor (SSRI) treatment reduces amyloid burden or improves cognitive function in humans, addressing a gap between preclinical findings and clinical evidence. While animal models suggest SSRIs may lower amyloid-beta levels and improve cognition, human data remain controversial. The authors aimed to evaluate the impact of SSRI treatment on amyloid pathology and cognitive performance in both cognitively normal and cognitively impaired individuals using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The researchers analyzed data from 1,149 participants across four ADNI phases who underwent at least one 18F-Florbetapir positron emission tomography (PET) scan. The cohort included 755 cognitively impaired subjects (160 with Alzheimer’s dementia [AD] and 595 with mild cognitive impairment [MCI]) and 394 cognitively normal controls. Participants were categorized into groups with a history of SSRI treatment (SSRI+) and those without (SSRI−). Amyloid burden was quantified using standardized uptake value ratios (SUVR), and cognitive status was assessed via the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS). Statistical analyses compared baseline and longitudinal changes in SUVR and ADAS scores between treatment groups, adjusting for covariates such as age, gender, and education. Subgroup analyses also examined the influence of depression history and specific SSRI types. The results demonstrated no significant differences in baseline amyloid burden (SUVR) between SSRI-treated and untreated groups across all diagnostic categories (AD, MCI, and cognitively normal). Similarly, SSRI treatment showed no beneficial effect on baseline or follow-up ADAS scores. Longitudinal analysis revealed no significant differences in the rate of amyloid accumulation or cognitive decline between SSRI+ and SSRI− groups over multiple follow-up periods. Although a dose-dependent inverse correlation was observed between medication duration and SUVR, this did not translate to a clinically significant reduction in amyloid load compared to untreated controls. Furthermore, no differences were found based on specific SSRI types or the presence of a depression history. The study concludes that chronic SSRI treatment does not confer beneficial effects on amyloid burden or cognitive performance in humans, contradicting optimistic preclinical data. These findings suggest that SSRIs are not effective as disease-modifying therapies for Alzheimer’s disease or related cognitive impairments. The results highlight the limitations of extrapolating animal model outcomes to human clinical applications and indicate that drug repurposing of SSRIs for AD pathology reduction is not supported by current imaging and cognitive evidence.

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• cognitive impairment