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Title: Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults

Importance of this Paper: The use of anticholinergic (AC) medication is linked to cognitive impairment and an increased risk of dementia. To our knowledge, this is the first study to investigate the association between AC medication use and neuroimaging biomarkers of brain metabolism and atrophy as a proxy for understanding the underlying biology of the clinical effects of AC medications. Objective: To assess the association between AC medication use and cognition, glucose metabolism, and brain atrophy in cognitively normal older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Indiana Memory and Aging Study (IMAS). Design, Setting, and Participants: The ADNI and IMAS are longitudinal studies with cognitive, neuroimaging, and other data collected at regular intervals in clinical and academic research settings. For the participants in the ADNI, visits are repeated 3, 6, and 12 months after the baseline visit and then annually. For the participants in the IMAS, visits are repeated every 18 months after the baseline visit (402 cognitively normal older adults in the ADNI and 49 cognitively normal older adults in the IMAS were included in the present analysis). Participants were either taking (hereafter referred to as the AC + participants [52 from the ADNI andmore » 8 from the IMAS]) or not taking (hereafter referred to as the AC - participants [350 from the ADNI and 41 from the IMAS]) at least 1 medication with medium or high AC activity. Data analysis for this study was performed in November 2015. Main Outcomes and Measures: Cognitive scores, mean fludeoxyglucose F 18 standardized uptake value ratio (participants from the ADNI only), and brain atrophy measures from structural magnetic resonance imaging were compared between AC + participants and AC - participants after adjusting for potential confounders. The total AC burden score was calculated and was related to target measures. The association of AC use and longitudinal clinical decline (mean [SD] follow-up period, 32.1 [24.7] months [range, 6-108 months]) was examined using Cox regression. Results: The 52 AC + participants (mean [SD] age, 73.3 [6.6] years) from the ADNI showed lower mean scores on Weschler Memory Scale–Revised Logical Memory Immediate Recall (raw mean scores: 13.27 for AC + participants and 14.16 for AC - participants; P = .04) and the Trail Making Test Part B (raw mean scores: 97.85 seconds for AC + participants and 82.61 seconds for AC - participants; P = .04) and a lower executive function composite score (raw mean scores: 0.58 for AC + participants and 0.78 for AC - participants; P = .04) than the 350 AC - participants (mean [SD] age, 73.3 [5.8] years) from the ADNI. Reduced total cortical volume and temporal lobe cortical thickness and greater lateral ventricle and inferior lateral ventricle volumes were seen in the AC + participants relative to the AC - participants. Conclusions and Relevance of this Paper: The use of AC medication was associated with increased brain atrophy and dysfunction and clinical decline. Thus and finally, use of AC medication among older adults should likely be discouraged if alternative therapies are available.« less
Authors:
 [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [3] ;  [4] ;  [4] ;  [5] ;  [6] ;  [7] ;  [1]
  1. Indiana Univ. School of Medicine, Indianapolis, IN (United States)
  2. Indiana Univ. School of Medicine, Indianapolis, IN (United States); Indiana Univ. Center for Aging Research, Indianapolis, IN (United States); Regenstrief Inst. Inc., Indianapolis, IN (United States); Eskenzai Health, Indianapolis, IN (United States)
  3. Univ. of Washington, Seattle, WA (United States)
  4. Mayo Clinic, Rochester, MN (United States)
  5. Univ. of California, Berkeley, CA (United States)
  6. Univ. of Southern California, San Diego, CA (United States)
  7. Univ. of California, San Francisco, CA (United States); Dept. of Veterans Affairs Medical Center, San Francisco, CA (United States)
Publication Date:
Grant/Contract Number:
AC02-05CH11231; U01 AG024904; K01 AG049050; P30 AG10133; P30 AG010129; R01 AG19771; K01 AG030514; W81XWH-12-2-0012
Type:
Accepted Manuscript
Journal Name:
JAMA Neurology
Additional Journal Information:
Journal Volume: 73; Journal Issue: 6; Journal ID: ISSN 2168-6149
Publisher:
American Medical Association
Research Org:
Indiana Univ. School of Medicine, Indianapolis, IN (United States); Univ. of California, Berkeley, CA (United States)
Sponsoring Org:
USDOE; National Inst. of Health (NIH) (United States); USDOD
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES
OSTI Identifier:
1379374

Risacher, Shannon L., McDonald, Brenna C., Tallman, Eileen F., West, John D., Farlow, Martin R., Unverzagt, Fredrick W., Gao, Sujuan, Boustani, Malaz, Crane, Paul K., Petersen, Ronald C., Jack, Clifford R., Jagust, William J., Aisen, Paul S., Weiner, Michael W., and Saykin, Andrew J.. Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults. United States: N. p., Web. doi:10.1001/jamaneurol.2016.0580.
Risacher, Shannon L., McDonald, Brenna C., Tallman, Eileen F., West, John D., Farlow, Martin R., Unverzagt, Fredrick W., Gao, Sujuan, Boustani, Malaz, Crane, Paul K., Petersen, Ronald C., Jack, Clifford R., Jagust, William J., Aisen, Paul S., Weiner, Michael W., & Saykin, Andrew J.. Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults. United States. doi:10.1001/jamaneurol.2016.0580.
Risacher, Shannon L., McDonald, Brenna C., Tallman, Eileen F., West, John D., Farlow, Martin R., Unverzagt, Fredrick W., Gao, Sujuan, Boustani, Malaz, Crane, Paul K., Petersen, Ronald C., Jack, Clifford R., Jagust, William J., Aisen, Paul S., Weiner, Michael W., and Saykin, Andrew J.. 2016. "Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults". United States. doi:10.1001/jamaneurol.2016.0580. https://www.osti.gov/servlets/purl/1379374.
@article{osti_1379374,
title = {Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults},
author = {Risacher, Shannon L. and McDonald, Brenna C. and Tallman, Eileen F. and West, John D. and Farlow, Martin R. and Unverzagt, Fredrick W. and Gao, Sujuan and Boustani, Malaz and Crane, Paul K. and Petersen, Ronald C. and Jack, Clifford R. and Jagust, William J. and Aisen, Paul S. and Weiner, Michael W. and Saykin, Andrew J.},
abstractNote = {Importance of this Paper: The use of anticholinergic (AC) medication is linked to cognitive impairment and an increased risk of dementia. To our knowledge, this is the first study to investigate the association between AC medication use and neuroimaging biomarkers of brain metabolism and atrophy as a proxy for understanding the underlying biology of the clinical effects of AC medications. Objective: To assess the association between AC medication use and cognition, glucose metabolism, and brain atrophy in cognitively normal older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Indiana Memory and Aging Study (IMAS). Design, Setting, and Participants: The ADNI and IMAS are longitudinal studies with cognitive, neuroimaging, and other data collected at regular intervals in clinical and academic research settings. For the participants in the ADNI, visits are repeated 3, 6, and 12 months after the baseline visit and then annually. For the participants in the IMAS, visits are repeated every 18 months after the baseline visit (402 cognitively normal older adults in the ADNI and 49 cognitively normal older adults in the IMAS were included in the present analysis). Participants were either taking (hereafter referred to as the AC+ participants [52 from the ADNI and 8 from the IMAS]) or not taking (hereafter referred to as the AC- participants [350 from the ADNI and 41 from the IMAS]) at least 1 medication with medium or high AC activity. Data analysis for this study was performed in November 2015. Main Outcomes and Measures: Cognitive scores, mean fludeoxyglucose F 18 standardized uptake value ratio (participants from the ADNI only), and brain atrophy measures from structural magnetic resonance imaging were compared between AC+ participants and AC- participants after adjusting for potential confounders. The total AC burden score was calculated and was related to target measures. The association of AC use and longitudinal clinical decline (mean [SD] follow-up period, 32.1 [24.7] months [range, 6-108 months]) was examined using Cox regression. Results: The 52 AC+ participants (mean [SD] age, 73.3 [6.6] years) from the ADNI showed lower mean scores on Weschler Memory Scale–Revised Logical Memory Immediate Recall (raw mean scores: 13.27 for AC+ participants and 14.16 for AC- participants; P = .04) and the Trail Making Test Part B (raw mean scores: 97.85 seconds for AC+ participants and 82.61 seconds for AC- participants; P = .04) and a lower executive function composite score (raw mean scores: 0.58 for AC+ participants and 0.78 for AC- participants; P = .04) than the 350 AC- participants (mean [SD] age, 73.3 [5.8] years) from the ADNI. Reduced total cortical volume and temporal lobe cortical thickness and greater lateral ventricle and inferior lateral ventricle volumes were seen in the AC+ participants relative to the AC- participants. Conclusions and Relevance of this Paper: The use of AC medication was associated with increased brain atrophy and dysfunction and clinical decline. Thus and finally, use of AC medication among older adults should likely be discouraged if alternative therapies are available.},
doi = {10.1001/jamaneurol.2016.0580},
journal = {JAMA Neurology},
number = 6,
volume = 73,
place = {United States},
year = {2016},
month = {4}
}