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JAMA Neurol. 2016 Jun 1;73(6):721-32. doi: 10.1001/jamaneurol.2016.0580.

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

Author information

1
Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indiana University Health Neuroscience Center, Indianapolis2Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis.
2
Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis3Department of Neurology, Indiana University School of Medicine, Indianapolis.
3
Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis4Department of Psychiatry, Indiana University School of Medicine, Indianapolis.
4
Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis5Department of Biostatistics, Indiana University School of Medicine, Indianapolis.
5
Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis6Indiana University Center for Aging Research, Indianapolis7Regenstrief Institute Inc, Indianapolis, Indiana8Eskenzai Health, Indianapolis, Indiana.
6
Department of Internal Medicine, University of Washington, Seattle.
7
Department of Neurology, Mayo Clinic, Rochester, Minnesota.
8
Department of Radiology, Mayo Clinic, Rochester, Minnesota.
9
Department of Neurology, University of California-Berkeley, Berkeley.
10
Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego.
11
Departments of Radiology, Medicine, and Psychiatry, University of California-San Francisco, San Francisco15Department of Veterans Affairs Medical Center, San Francisco, California.

Abstract

IMPORTANCE:

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:

The use of AC medication was associated with increased brain atrophy and dysfunction and clinical decline. Thus, use of AC medication among older adults should likely be discouraged if alternative therapies are available.

PMID:
27088965
PMCID:
PMC5029278
DOI:
10.1001/jamaneurol.2016.0580
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Disclosures: Dr Farlow reports grant research support from Accera, Biogen, Eisai, Eli Lilly, Genentech, Roche, Lundbeck, Chase Pharmaceuticals, and Boehringer-Ingelheim and being a consultant for or on the advisory or data and safety monitoring boards of Accera, Alltech, Avanir, Biogen, Eisai Medical Research Inc, FORUM Pharmaceuticals, Genentech Inc, Grifols, Helicon Inc Research, Lundbeck, Medavante, Medivation Inc, Merck and Company Inc, Medtronic, Neurotrope Biosciences, Novartis, Pfizer, QR Pharma, Axovant Sciences Inc, Roche, Sanofi-Aventis, Schering-Plough, Takeda, Toyama Pharmaceutical, Pharm, Eli Lilly and Company, and UCB Pharma. Dr Petersen serves on the advisory boards of Pfizer Inc and Janssen Alzheimer Immunotherapy and is a consultant for Roche Incorporated, Merck, Genentech, and Biogen. He receives support from the National Institute on Aging (grants U01-AG006786, P50-AGG016574, R01-AG011378, and U01-AG024904) and publishing royalties from Oxford University Press. Dr Jack serves as a consultant for Eli Lilly and Company and receives research support from the National Institute on Aging (grants R01 AG11378 and R01 AG041851) and the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Foundation. Dr Jagust serves on the scientific advisory boards of Genentech and Banner/ Genentech and was a consultant for Synarc, Siemens Medical, Genentech, F. Hoffman–La Roche, and Novartis. He receives research support from Avid Radiopharmaceuticals, the Rainwater Foundation, and the National Institutes of Health (NIH) (grants AG034570, AG025303, AG044292, AG012345, AG021028, AG031563, AG019724, AG030048, AG032306, and AG024904). Dr Aisen serves on the scientific advisory boards of Novartis and Biogen and has been a consultant for Elan Corporation, Wyeth, Eisai Inc, Schering-Plough Corp, Bristol-Myers Squibb, Eli Lilly and Company, Roche, Amgen, Genentech Inc, Abbott, Pfizer Inc, Novartis, Bayer, Medivation Inc, Daiichi Sankyo, Astellas, Bainippon, Biomarin, Solvay, Ostuka, AstraZeneca, and Janssen. He receives research support from Baxter, Pfizer, Janssen, and Eli Lilly and Company, as well as from the National Institute on Aging (grants U01-AG10483, U01 AG024904, R01 AG030048, and R01 AG16381). Dr Weiner serves on the scientific advisory boards for Pfizer, BOLT International, Neurotrope Bioscience, Eli Lilly and Company, the University of Pennsylvania’s Neuroscience of Behavior Initiative, the National Brain Research Centre, India, and the ADNI and is a consultant for Synarc, Pfizer, Janssen, KLJ Associates, Easton Associates, Harvard University, the University of California, Los Angeles (UCLA), the Alzheimer’s Drug Discovery Foundation, Avid Radiopharmaceuticals, Clearview Healthcare Partners, Perceptive Informatics, Smartfish AS, Decision Resources Inc, Neurotrope Bioscience, Araclon, Merck, Defined Health, and Genentech. He receives research support from Avid Radiopharmceuticals, Eli Lilly and Company, the NIH, the US Department of Defense, and the Veterans Administration. He also has received travel funding or speaker honoraria from Pfizer, Paul Sabatier University, the MCI Group France, eDreams, the Neuroscience School of Advanced Studies, Danone Trading, BV, CTAD ANT Congrès, Kenes International, the Aging and Disability Resource Center, UCLA, the University of California, San Diego, the Sanofi-Aventis Group, University Center Hospital, Toulouse, Araclon, AC Immune, Eli Lilly and Company, the New York Academy of Sciences, the National Brain Research Center, Indiana for Johns Hopkins Medicine, the Consortium for Multiple Sclerosis Centers, Northwestern University, and the University of Pennsylvania. Dr Saykin serves on scientific advisory boards of Siemens Healthcare and Eli Lilly and Company and was a consultant for Baxter Bioscience, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer Inc, Siemens Healthcare, Dartmouth Medical School, the University of Michigan, the University of Vermont, Vanderbilt University, and Brigham and Women’s Hospital/ Massachusetts General Hospital. He has received research support from Siemens Medical Solutions, Welch Allyn Inc, the Foundation for the NIH, and the NIH (grants R01 AG19771, R01 CA101318, R01 LM011360, RC2 AG036535, P30 AG10133, and U01 AG032984). He has also received travel support and/or speaker honoraria from Siemens Healthcare. No other disclosures are reported.

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