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. 2022 Jun 23:14:883256.
doi: 10.3389/fnagi.2022.883256. eCollection 2022.

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

Yvonne Bouter  1 , Caroline Bouter  2
Affiliations

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

Yvonne Bouter et al. Front Aging Neurosci. .

Abstract

Preclinical studies indicate that selective serotonin reuptake inhibitors (SSRI) have beneficial effects on Alzheimer-related pathologies. Therefore, the aim of this study was to evaluate the influence of SSRI-treatment on amyloid burden in 18F-Florbetapir-positron emission tomography (PET) and on cognition in cognitively normal and cognitively impaired subjects. We included n = 755 cognitively impaired and n = 394 cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) that underwent at least one 18F-Florbetapir-PET. Standardized uptake ratios (SUVR) and the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS) scores as well as follow-up results were compared between subgroups with a history of SSRI-treatment (SSRI+) and without SSRI-treatment (SSRI-) as well as in subgroups of SSRI+/Depression+ and SSRI+/Depression- and SSRI-/Depression+ and SSRI-/Depression-. 18F-Florbetapir-PET did not show significant differences of SUVR between the SSRI+ and SSRI- groups in both, cognitively impaired and cognitively normal participants. There were no differences in subgroups of SSRI+/Depression+ and SSRI+/Depression- and SSRI-/Depression+ and SSRI-/Depression-. However, SUVR showed a dose-dependent inverse correlation to the duration of medication in cognitively normal and in cognitively impaired patients. SRRI-treatment did not show an effect on ADAS scores. Furthermore, there was no effect on follow-up SUVR or on follow-up ADAS scores. Overall, SSRI-treatment did not show beneficial effects on amyloid load nor on cognition.

Keywords: Alzheheimer’s disease; amyloid-PET imaging; florbetaben; positron emission tomography; selective serotonin reuptake inhibitors.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
ADNI cohort. 18F-Florbetapir-PET was performed in n = 1296 ADNI participants. N = 147 subjects were excluded from our study due to missing data or stopped SSRI medication as well as patients with subjective memory deficits that did not meet criteria of AD or MCI. A total of n = 1149 subjects from ADNI phases 1, GO, 2 and 3 were included in this study. All subjects were categorized according to their diagnosis in AD, MCI, or CN. Groups were further subdivided in subjects with prior SSRI-treatment (SSRI+) and subjects with no history of SSRI-treatment (SSRI−). AD, Alzheimer’s dementia; MCI, mild cognitive impairment; CN, cognitively normal controls.
FIGURE 2
FIGURE 2
18F-Florbetapir uptake in SSRI-treated and untreated subjects. (A) SUVR was significantly higher in AD-patients compared to MCI patients as well as between AD or MCI patients compared to CN (ANCOVA). SUVR did not show significant differences between SSRI-treated (SSRI+) and untreated (SSRI−) subjects regardless of the diagnosis (Mann–Whitney U test; red bars represent median ± interquartile range). (B) SUVR showed a time-dependent inverse correlation to the duration of medication in cognitively normal patients. (C) SUVR also showed a time-dependent negative relation to the duration of medication in cognitively impaired patients. Spearman correlation; *p < 0.05; **p < 0.01. SUVR, standard uptake value ratio; CN, cognitively normal controls; CI, cognitively impaired patients; AD, Alzheimer’s disease; MCI, mild cognitive impairment.
FIGURE 3
FIGURE 3
18F-Florbetapir uptake in SSRI-treated and untreated subjects with and without history of depression. No significant differences between SSRI-treated and untreated subjects with or without depression were detected regardless of the diagnosis (Kruskal–Wallis test; red bars represent median ± interquartile range. AD, Alzheimer’s disease; MCI, mild cognitive impairment; CN, cognitively normal controls.
FIGURE 4
FIGURE 4
Follow up. (A) Differences of SUVR between follow-up and baseline PET did not show significant differences between SSRI-treated and untreated subjects (Mann–Whitney U test). (B) Differences of ADAS between follow-up and baseline examination did not show significant differences between SSRI-treated and untreated subjects (Mann–Whitney U test). Red bars represent median ± interquartile range.
FIGURE 5
FIGURE 5
ADAS cognition test results. (A) ADAS scores correlated to SUVR results (Spearman correlation; ***p < 0.001). (B) SSRI-treatment did not influence cognition. ADAS was significantly higher in AD patients compared to MCI and both, AD patients and MCI patients showed higher ADAS scores compared to CN (ANCOVA). Red bars represent median with interquartile range. AD, Alzheimer’s disease; MCI, mild cognitive impairment; CN, cognitively normal controls.
FIGURE 6
FIGURE 6
ApoE4 carriers. ApoE4 carriers showed significantly higher SUVR compared to non-carriers in cognitively impaired patients as well as in cognitively normal subjects (Mann–Whitney U test; ***p < 0.001). There were no differences between ApoE4 carriers in SSRI+ and SSRI− groups (Mann–Whitney U test). Red bars represent median ± interquartile range.
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