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 onWeschler 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 721-732 |
| Number of pages | 12 |
| Journal | JAMA Neurology |
| Volume | 73 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2016 |
ASJC Scopus subject areas
- Clinical Neurology
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In: JAMA Neurology, Vol. 73, No. 6, 06.2016, p. 721-732.
Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults
AU - Risacher, Shannon L.
AU - McDonald, Brenna C.
AU - Tallman, Eileen F.
AU - West, John D.
AU - Farlow, Martin R.
AU - Unverzagt, Fredrick W.
AU - Gao, Sujuan
AU - Boustani, Malaz
AU - Crane, Paul K.
AU - Petersen, Ronald C.
AU - Jack, Clifford R.
AU - Jagust, William J.
AU - Aisen, Paul S.
AU - Weiner, Michael W.
AU - Saykin, Andrew J.
AU - Trojanowki, John Q.
AU - Toga, Arthur W.
AU - Beckett, Laurel
AU - Green, Robert C.
AU - Morris, John
AU - Shaw, Leslie M.
AU - Khachaturian, Zaven
AU - Sorensen, Greg
AU - Carrillo, Maria
AU - Kuller, Lew
AU - Raichle, Marc
AU - Paul, Steven
AU - Davies, Peter
AU - Fillit, Howard
AU - Hefti, Franz
AU - Holtzman, Davie
AU - Mesulam, Marek Marsel
AU - Potter, William
AU - Snyder, Peter J.
AU - Schwartz, Adam
AU - Montine, Tom
AU - Thomas, Ronald G.
AU - Donohue, Michael
AU - Walter, Sarah
AU - Gessert, Devon
AU - Sather, Tamie
AU - Jiminez, Gus
AU - Balasubramanian, Archana B.
AU - Mason, Jennifer
AU - Sim, Iris
AU - Harvey, Danielle
AU - Bernstein, Matthew
AU - Fox, Nick
AU - Thompson, Paul
AU - Schuff, Norbert
AU - DeCarli, Charles
AU - Borowski, Bret
AU - Gunter, Jeff
AU - Senjem, Matt
AU - Vemuri, Prashanthi
AU - Jones, David
AU - Kantarci, Kejal
AU - Ward, Chad
AU - Koeppe, Robert A.
AU - Foster, Norm
AU - Reiman, Eric M.
AU - Chen, Kewei
AU - Mathis, Chet
AU - Landau, Susan
AU - Cairns, Nigel J.
AU - Householder, Erin
AU - Taylor-Reinwald, Lisa
AU - Lee, Virginia
AU - Korecka, Magdalena
AU - Figurski, Michal
AU - Crawford, Karen
AU - Neu, Scott
AU - Foroud, Tatiana M.
AU - Potkin, Steven G.
AU - Shen, Li
AU - Faber, Kelley
AU - Kim, Sungeun
AU - Nho, Kwangsik
AU - Thal, Lean
AU - Thal, Leon
AU - Buckholtz, Neil
AU - Albert, Marylyn
AU - Frank, Richard
AU - Hsiao, John
AU - Kaye, Jeffrey
AU - Quinn, Joseph
AU - Silbert, Lisa
AU - Lind, Betty
AU - Carter, Raina
AU - Dolen, Sara
AU - Schneider, Lon S.
AU - Pawluczyk, Sonia
AU - Beccera, Mauricio
AU - Teodoro, Liberty
AU - Spann, Bryan M.
AU - Brewer, James
AU - Vanderswag, Helen
AU - Fleisher, Adam
AU - Heidebrink, Judith L.
AU - Lord, Joanne L.
AU - Mason, Sara S.
AU - Albers, Colleen S.
AU - Knopman, David
AU - Johnson, Kris
AU - Doody, Rachelle S.
AU - Villanueva-Meyer, Javier
AU - Chowdhury, Munir
AU - Rountree, Susan
AU - Dang, Mimi
AU - Stern, Yaakov
AU - Honig, Lawrence S.
AU - Bell, Karen L.
AU - Ances, Beau
AU - Carroll, Maria
AU - Creech, Mary L.
AU - Franklin, Erin
AU - Mintun, Mark A.
AU - Schneider, Stacy
AU - Oliver, Angela
AU - Marson, Daniel
AU - Griffith, Randall
AU - Clark, David
AU - Geldmacher, David
AU - Brockington, John
AU - Roberson, Erik
AU - Love, Marissa Natelson
AU - Grossman, Hillel
AU - Mitsis, Effie
AU - Shah, Raj C.
AU - De Toledo-Morrell, Leyla
AU - Duara, Ranjan
AU - Varon, Daniel
AU - Greig, Maria T.
AU - Roberts, Peggy
AU - Onyike, Chiadi
AU - D'Agostino, Daniel
AU - Kielb, Stephanie
AU - Galvin, James E.
AU - Cerbone, Brittany
AU - Michel, Christina A.
AU - Pogorelec, Dana M.
AU - Rusinek, Henry
AU - De Leon, Mony J.
AU - Glodzik, Lidia
AU - De Santi, Susan
AU - Murali Doraiswamy, P.
AU - Petrella, Jeffrey R.
AU - Borges-Neto, Salvador
AU - Wong, Terence Z.
AU - Coleman, Edward
AU - Arnold, Steven E.
AU - Karlawish, Jason H.
AU - Wolk, David
AU - Clark, Christopher M.
AU - Smith, Charles D.
AU - Jicha, Greg
AU - Hardy, Peter
AU - Sinha, Partha
AU - Oates, Elizabeth
AU - Conrad, Gary
AU - Lopez, Oscar L.
AU - Oakley, Mary Ann
AU - Simpson, Donna M.
AU - Porsteinsson, Anton P.
AU - Goldstein, Bonnie S.
AU - Martin, Kim
AU - Makino, Kelly M.
AU - Saleem Ismail, M.
AU - Brand, Connie
AU - Mulnard, Ruth A.
AU - Thai, Gaby
AU - McAdams-Ortiz, Catherine
AU - Womack, Kyle
AU - Mathews, Dana
AU - Quiceno, Mary
AU - Levey, Allan I.
AU - Lah, James J.
AU - Cellar, Janet S.
AU - Burns, Jeffrey M.
AU - Swerdlow, Russell H.
AU - Brooks, William M.
AU - Apostolova, Liana
AU - Tingus, Kathleen
AU - Woo, Ellen
AU - Silverman, Daniel H S
AU - Lu, Po H.
AU - Bartzokis, George
AU - Graff-Radford, Neill R.
AU - Parfitt, Francine
AU - Kendall, Tracy
AU - Johnson, Heather
AU - Hake, Ann Marie
AU - Matthews, Brandy R.
AU - Brosch, Jared R.
AU - Herring, Scott
AU - Hunt, Cynthia
AU - Van Dyck, Christopher H.
AU - Carson, Richard E.
AU - MacAvoy, Martha G.
AU - Varma, Pradeep
AU - Chertkow, Howard
AU - Bergman, Howard
AU - Hosein, Chris
AU - Black, Sandra
AU - Stefanovic, Bojana
AU - Caldwell, Curtis
AU - Hsiung, Ging Yuek Robin
AU - Feldman, Howard
AU - Mudge, Benita
AU - Assaly, Michele
AU - Finger, Elizabeth
AU - Pasternack, Stephen
AU - Rachisky, Irina
AU - Trost, Dick
AU - Kertesz, Andrew
AU - Bernick, Charles
AU - Munic, Donna
AU - Lipowski, Kristine
AU - Weintraub, Sandra
AU - Bonakdarpour, Borna
AU - Kerwin, Diana
AU - Wu, Chuang Kuo
AU - Johnson, Nancy
AU - Sadowsky, Carl
AU - Villena, Teresa
AU - Turner, Raymond Scott
AU - Johnson, Kathleen
AU - Reynolds, Brigid
AU - Sperling, Reisa A.
AU - Johnson, Keith A.
AU - Marshall, Gad
AU - Yesavage, Jerome
AU - Taylor, Joy L.
AU - Lane, Barton
AU - Rosen, Allyson
AU - Tinklenberg, Jared
AU - Sabbagh, Marwan N.
AU - Belden, Christine M.
AU - Jacobson, Sandra A.
AU - Sirrel, Sherye A.
AU - Kowall, Neil
AU - Killiany, Ronald
AU - Budson, Andrew E.
AU - Norbash, Alexander
AU - Johnson, Patricia Lynn
AU - Obisesan, Thomas O.
AU - Wolday, Saba
AU - Allard, Joanne
AU - Lerner, Alan
AU - Ogrocki, Paula
AU - Tatsuoka, Curtis
AU - Fatica, Parianne
AU - Fletcher, Evan
AU - Maillard, Pauline
AU - Olichney, John
AU - Carmichael, Owen
AU - Kittur, Smita
AU - Borrie, Michael
AU - Lee, T. Y.
AU - Bartha, Rob
AU - Johnson, Sterling
AU - Asthana, Sanjay
AU - Carlsson, Cynthia M.
AU - Preda, Adrian
AU - Nguyen, Dana
AU - Tariot, Pierre
AU - Burke, Anna
AU - Trncic, Nadira
AU - Reeder, Stephanie
AU - Bates, Vernice
AU - Capote, Horacio
AU - Rainka, Michelle
AU - Scharre, Douglas W.
AU - Kataki, Maria
AU - Adeli, Anahita
AU - Zimmerman, Earl A.
AU - Celmins, Dzintra
AU - Brown, Alice D.
AU - Pearlson, Godfrey D.
AU - Blank, Karen
AU - Anderson, Karen
AU - Flashman, Laura A.
AU - Seltzer, Marc
AU - Hynes, Mary L.
AU - Santulli, Robert B.
AU - Sink, Kaycee M.
AU - Gordineer, Leslie
AU - Williamson, Jeff D.
AU - Garg, Pradeep
AU - Watkins, Franklin
AU - Ott, Brian R.
AU - Querfurth, Henry
AU - Tremont, Geoffrey
AU - Salloway, Stephen
AU - Malloy, Paul
AU - Correia, Stephen
AU - Rosen, Howard J.
AU - Miller, Bruce L.
AU - Perry, David
AU - Mintzer, Jacobo
AU - Spicer, Kenneth
AU - Bachman, David
AU - Pasternak, Stephen
AU - Rachinsky, Irina
AU - Rogers, John
AU - Drost, Dick
AU - Pomara, Nunzio
AU - Hernando, Raymundo
AU - Sarrael, Antero
AU - Schultz, Susan K.
AU - Boles Ponto, Laura L.
AU - Shim, Hyungsub
AU - Smith, Karen Ekstam
AU - Relkin, Norman
AU - Chaing, Gloria
AU - Lin, Michael
AU - Ravdin, Lisa
AU - Smith, Amanda
AU - Ashok Raj, Balebail
AU - Fargher, Kristin
AU - Neylan, Thomas
AU - Grafman, Jordan
AU - Davis, Melissa
AU - Morrison, Rosemary
AU - Hayes, Jacqueline
AU - Finley, Shannon
AU - Friedl, Karl
AU - Fleischman, Debra
AU - Arfanakis, Konstantinos
AU - Doraiswamy, P. Murali
AU - James, Olga
AU - Goldstei, Bonnie
AU - Martin, Kimberly S.
AU - Massoglia, Dino
AU - Brawman-Mintzer, Olga
AU - Martinez, Walter
AU - Ros, Howard
AU - Behan, Kelly
AU - Sirrel, Sherye A.
AU - Johnson, Sterling C.
AU - Fruehling, J. Jay
AU - Harding, Sandra
AU - Peskind, Elaine R.
AU - Petrie, Eric C.
AU - Li, Gail
AU - Yesavage, Jerome A.
AU - Furst, Ansgar J.
AU - Chao, Steven
N1 - Publisher Copyright: Copyright 2016 American Medical Association. All rights reserved.
PY - 2016/6
Y1 - 2016/6
N2 - 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 onWeschler 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.
AB - 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 onWeschler 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.
UR - http://www.scopus.com/inward/record.url?scp=84974603577&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84974603577&partnerID=8YFLogxK
U2 - 10.1001/jamaneurol.2016.0580
DO - 10.1001/jamaneurol.2016.0580
M3 - Article
C2 - 27088965
AN - SCOPUS:84974603577
SN - 2168-6149
VL - 73
SP - 721
EP - 732
JO - JAMA Neurology
JF - JAMA Neurology
IS - 6
ER -