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

Publication ,  Journal Article
Risacher, SL; McDonald, BC; Tallman, EF; West, JD; Farlow, MR; Unverzagt, FW; Gao, S; Boustani, M; Crane, PK; Petersen, RC; Jack, CR ...
Published in: JAMA Neurol
June 1, 2016

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.

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Published In

JAMA Neurol

DOI

EISSN

2168-6157

Publication Date

June 1, 2016

Volume

73

Issue

6

Start / End Page

721 / 732

Location

United States

Related Subject Headings

  • Proportional Hazards Models
  • Positron-Emission Tomography
  • Neuropsychological Tests
  • Memory Disorders
  • Male
  • Magnetic Resonance Imaging
  • Humans
  • Fluorodeoxyglucose F18
  • Female
  • Executive Function
 

Citation

APA
Chicago
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MLA
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Risacher, S. L., McDonald, B. C., Tallman, E. F., West, J. D., Farlow, M. R., Unverzagt, F. W., … Alzheimer’s Disease Neuroimaging Initiative, . (2016). Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults. JAMA Neurol, 73(6), 721–732. https://doi.org/10.1001/jamaneurol.2016.0580
Risacher, Shannon L., Brenna C. McDonald, Eileen F. Tallman, John D. West, Martin R. Farlow, Fredrick W. Unverzagt, Sujuan Gao, et al. “Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults.JAMA Neurol 73, no. 6 (June 1, 2016): 721–32. https://doi.org/10.1001/jamaneurol.2016.0580.
Risacher SL, McDonald BC, Tallman EF, West JD, Farlow MR, Unverzagt FW, et al. Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults. JAMA Neurol. 2016 Jun 1;73(6):721–32.
Risacher, Shannon L., et al. “Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults.JAMA Neurol, vol. 73, no. 6, June 2016, pp. 721–32. Pubmed, doi:10.1001/jamaneurol.2016.0580.
Risacher SL, McDonald BC, Tallman EF, West JD, Farlow MR, Unverzagt FW, Gao S, Boustani M, Crane PK, Petersen RC, Jack CR, Jagust WJ, Aisen PS, Weiner MW, Saykin AJ, Alzheimer’s Disease Neuroimaging Initiative. Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults. JAMA Neurol. 2016 Jun 1;73(6):721–732.

Published In

JAMA Neurol

DOI

EISSN

2168-6157

Publication Date

June 1, 2016

Volume

73

Issue

6

Start / End Page

721 / 732

Location

United States

Related Subject Headings

  • Proportional Hazards Models
  • Positron-Emission Tomography
  • Neuropsychological Tests
  • Memory Disorders
  • Male
  • Magnetic Resonance Imaging
  • Humans
  • Fluorodeoxyglucose F18
  • Female
  • Executive Function