TY - JOUR
T1 - Psychotropic Medication and Cognitive, Functional, and Neuropsychiatric Outcomes in Alzheimer's Disease (AD)
AU - Oh, Esther S.
AU - Rosenberg, Paul B.
AU - Rattinger, Gail B.
AU - Stuart, Elizabeth A.
AU - Lyketsos, Constantine G.
AU - Leoutsakos, Jeannie Marie S.
N1 - Funding Information:
Funding Sources: National Institute of Aging (NIA) R01AG057725 (ESO), NIA K08AG029157 (PBR), NIA U01AG016976 (National Alzheimer's Coordinating Center) (CGL), NIA P50AG005146 and P30 AG066507 (Johns Hopkins Alzheimer's Disease Research Center) (CGL), National Institute of Mental Health U01MH066136 (CGL), and NIH Institutional Career Development Grant K12 HD043489 (GBR).The sponsors had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Funding Information:
Constantine G. Lyketsos grants: NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, Glaxo‐Smith‐Kline, Eisai, Pfizer, Astra‐Zeneca, Lilly, Ortho‐McNeil, Bristol‐Myers, Novartis, National Football League, Elan, Functional Neuromodulation, Bright Focus Foundation.
Funding Information:
The NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by the NIA‐funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG062428‐01 (PI James Leverenz, MD) P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P30 AG062421‐01 (PI Bradley Hyman, MD, PhD), P30 AG062422‐01 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P30 AG062429‐01(PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715‐01 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD).
Publisher Copyright:
© 2020 The American Geriatrics Society
PY - 2021/4
Y1 - 2021/4
N2 - BACKGROUND/OBJECTIVES: There are growing concerns about the safety and efficacy of psychotropic medications in Alzheimer's disease (AD). We sought to examine associations between psychotropic medication exposure and longitudinal change in cognitive, functional, and neuropsychiatric outcomes in a large clinical AD cohort. DESIGN: Longitudinal observational study. SETTING: National Alzheimer's Disease Coordinating Center combining data from 39 Alzheimer's disease centers. PARTICIPANTS: 8,034 participants with AD dementia. MEASUREMENTS: Mini-Mental State Exam (MMSE), Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), and Neuropsychiatric Inventory Questionnaire (NPI-Q) Total. Probability of exposure to medication (the propensity score, PS) calculated via logistic regression. Medication classes included all antipsychotics (atypical vs conventional), antidepressants (Selective Serotonin Reuptake Inhibitor [SSRI] vs non-SSRI), and benzodiazepines. Participants treated with a medication class were matched with participants not treated with that class with the closest-matched PS. The effect of medication treatment was assessed using linear mixed-effects models. RESULTS: Participants had a mean (SD) age of 75.5 (9.8) years, and mean (SD) scores of MMSE 21.3 (5.7), CDR-SB 5.5 (3.4), and NPI-Q Total 4.5 (4.4). Mean duration of follow-up was 2.9–3.3 years depending on medication class. Non-SSRI antidepressant use was associated with better CDR-SB (2-year difference in change-DIC: −0.38 [−0.61, −0.15], P =.001). Atypical antipsychotic use was associated with greater decline on MMSE (DIC: −0.91 [−1.54, −0.28] P =.005) and CDR-SB scores (DIC: 0.50 [0.14, 0.86], P =.006). Notably, no drug class was associated with better NPI-Q scores. CONCLUSIONS: Use of atypical antipsychotics was associated with poorer cognition and function, and no drug class was associated with improvement in neuropsychiatric symptoms.
AB - BACKGROUND/OBJECTIVES: There are growing concerns about the safety and efficacy of psychotropic medications in Alzheimer's disease (AD). We sought to examine associations between psychotropic medication exposure and longitudinal change in cognitive, functional, and neuropsychiatric outcomes in a large clinical AD cohort. DESIGN: Longitudinal observational study. SETTING: National Alzheimer's Disease Coordinating Center combining data from 39 Alzheimer's disease centers. PARTICIPANTS: 8,034 participants with AD dementia. MEASUREMENTS: Mini-Mental State Exam (MMSE), Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), and Neuropsychiatric Inventory Questionnaire (NPI-Q) Total. Probability of exposure to medication (the propensity score, PS) calculated via logistic regression. Medication classes included all antipsychotics (atypical vs conventional), antidepressants (Selective Serotonin Reuptake Inhibitor [SSRI] vs non-SSRI), and benzodiazepines. Participants treated with a medication class were matched with participants not treated with that class with the closest-matched PS. The effect of medication treatment was assessed using linear mixed-effects models. RESULTS: Participants had a mean (SD) age of 75.5 (9.8) years, and mean (SD) scores of MMSE 21.3 (5.7), CDR-SB 5.5 (3.4), and NPI-Q Total 4.5 (4.4). Mean duration of follow-up was 2.9–3.3 years depending on medication class. Non-SSRI antidepressant use was associated with better CDR-SB (2-year difference in change-DIC: −0.38 [−0.61, −0.15], P =.001). Atypical antipsychotic use was associated with greater decline on MMSE (DIC: −0.91 [−1.54, −0.28] P =.005) and CDR-SB scores (DIC: 0.50 [0.14, 0.86], P =.006). Notably, no drug class was associated with better NPI-Q scores. CONCLUSIONS: Use of atypical antipsychotics was associated with poorer cognition and function, and no drug class was associated with improvement in neuropsychiatric symptoms.
KW - Alzheimer's disease
KW - antidepressants
KW - antipsychotics
KW - benzodiazepines
KW - outcomes
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U2 - 10.1111/jgs.16970
DO - 10.1111/jgs.16970
M3 - Article
C2 - 33382921
AN - SCOPUS:85098516467
VL - 69
SP - 955
EP - 963
JO - Journal of the American Geriatrics Society
JF - Journal of the American Geriatrics Society
SN - 0002-8614
IS - 4
ER -