Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults

JAMA Neurology

Volumn 73, Issue 6, 2016, Pages 721-732

  Risacher, Shannon L ^a   McDonald, Brenna C ^a   Tallman, Eileen F ^a   West, John D ^a   Farlow, Martin R ^a,p   Unverzagt, Fredrick W ^a   Gao, Sujuan ^a   Boustani, Malaz ^a,b,c,d   Crane, Paul K ^e   Petersen, Ronald C ^f   Jack, Clifford R ^f   Jagust, William J ^g   Aisen, Paul S ^h,l   Weiner, Michael W ^i,j,k   Saykin, Andrew J ^a,p   Trojanowki, John Q ^m,ah   Toga, Arthur W ^h   Beckett, Laurel ⁿ   Green, Robert C ^o   Morris, John ^q   Shaw, Leslie M ^m,ah,ce   Khachaturian, Zaven ^ce   Sorensen, Greg ^r   Carrillo, Maria ^s   Kuller, Lew ^t   Raichle, Marc ^q   Paul, Steven ^u   Davies, Peter ^v   Fillit, Howard ^w   Hefti, Franz ^x   Holtzman, Davie ^q   Mesulam, Marek Marsel ^y   Potter, William ^z   Snyder, Peter J ^aa   Schwartz, Adam ^ab   Montine, Tom ^e   Thomas, Ronald G ^l   Donohue, Michael ^l   Walter, Sarah ^l   Gessert, Devon ^l   Sather, Tamie ^l   Jiminez, Gus ^l   Balasubramanian, Archana B ^l   Mason, Jennifer ^l   Sim, Iris ^l   Harvey, Danielle ^l,n   Bernstein, Matthew ^f   Fox, Nick ^ac   Thompson, Paul ^ad   Schuff, Norbert ^j   DeCarli, Charles ⁿ   Borowski, Bret ^f   Gunter, Jeff ^f   Senjem, Matt ^f   Vemuri, Prashanthi ^f   Jones, David ^f   Kantarci, Kejal ^f   Ward, Chad ^f   Koeppe, Robert A ^ae   Foster, Norm ^af   Reiman, Eric M ^ag   Chen, Kewei ^ag   Mathis, Chet ^t   Landau, Susan ^g   Cairns, Nigel J ^q   Householder, Erin ^q   Taylor Reinwald, Lisa ^q   Lee, Virginia ^ah   Korecka, Magdalena ^ah   Figurski, Michal ^ah   Crawford, Karen ^h   Neu, Scott ^h   Foroud, Tatiana M ^p   Potkin, Steven G ^ai   Shen, Li ^p   Faber, Kelley ^p   Kim, Sungeun ^p   Nho, Kwangsik ^p   Thal, Lean ^l   Thal, Leon ^l   Buckholtz, Neil ^aj   Albert, Marylyn ^ak   Frank, Richard ^al   Hsiao, John ^aj   Kaye, Jeffrey ^am   Quinn, Joseph ^am   Silbert, Lisa ^am   Lind, Betty ^am   Carter, Raina ^am   Dolen, Sara ^am   Schneider, Lon S ^h,cg   Pawluczyk, Sonia ^h   Beccera, Mauricio ^h   Teodoro, Liberty ^h   Spann, Bryan M ^h   Brewer, James ^l   Vanderswag, Helen ^l   Fleisher, Adam ^l   Heidebrink, Judith L ^ae   Lord, Joanne L ^ae   Mason, Sara S ^ae   Albers, Colleen S ^ae   Knopman, David ^ae   Johnson, Kris ^ae   Doody, Rachelle S ^an   Villanueva Meyer, Javier ^an   Chowdhury, Munir ^an   Rountree, Susan ^an   Dang, Mimi ^an   Stern, Yaakov ^ao   Honig, Lawrence S ^ao   Bell, Karen L ^ao   Ances, Beau ^q   Carroll, Maria ^q   Creech, Mary L ^q   Franklin, Erin ^q   Mintun, Mark A ^q   Schneider, Stacy ^q   Oliver, Angela ^q   Marson, Daniel ^ap   Griffith, Randall ^ap   Clark, David ^ap   Geldmacher, David ^ap   Brockington, John ^ap   Roberson, Erik ^ap   Love, Marissa Natelson ^ap   Grossman, Hillel ^aq   Mitsis, Effie ^aq   Shah, Raj C ^ar   De Toledo Morrell, Leyla ^ar   Duara, Ranjan ^as   Varon, Daniel ^as   Greig, Maria T ^as   Roberts, Peggy ^as   Onyike, Chiadi ^as   D'Agostino, Daniel ^as   Kielb, Stephanie ^as   Galvin, James E ^at   Cerbone, Brittany ^at   Michel, Christina A ^at   Pogorelec, Dana M ^at   Rusinek, Henry ^at   De Leon, Mony J ^at   Glodzik, Lidia ^at   De Santi, Susan ^at   Murali Doraiswamy, P ^au   Petrella, Jeffrey R ^au   Borges Neto, Salvador ^au   Wong, Terence Z ^au   Coleman, Edward ^au   Arnold, Steven E ^m   Karlawish, Jason H ^m   Wolk, David ^m   Clark, Christopher M ^m   Smith, Charles D ^av   Jicha, Greg ^av   Hardy, Peter ^av   Sinha, Partha ^av   Oates, Elizabeth ^av   Conrad, Gary ^av   Lopez, Oscar L ^t   Oakley, MaryAnn ^t   Simpson, Donna M ^t   Porsteinsson, Anton P ^av,aw   Goldstein, Bonnie S ^av   Martin, Kim ^av   Makino, Kelly M ^av   Saleem Ismail, M ^av   Brand, Connie ^av   Mulnard, Ruth A ^ai   Thai, Gaby ^ai   McAdams Ortiz, Catherine ^ai   Womack, Kyle ^aw   Mathews, Dana ^aw   Quiceno, Mary ^ax   Levey, Allan I ^ay   Lah, James J ^ay   Cellar, Janet S ^ay   Burns, Jeffrey M ^az   Swerdlow, Russell H ^az   Brooks, William M ^az   Apostolova, Liana ^ba   Tingus, Kathleen ^ba   Woo, Ellen ^ba   Silverman, Daniel H S ^ba   Lu, Po H ^ba   Bartzokis, George ^ba   Graff Radford, Neill R ^f   Parfitt, Francine ^f   Kendall, Tracy ^f   Johnson, Heather ^f   Hake, Ann Marie ^p   Matthews, Brandy R ^p   Brosch, Jared R ^p   Herring, Scott ^p   Hunt, Cynthia ^p   Van Dyck, Christopher H ^bb   Carson, Richard E ^bb   MacAvoy, Martha G ^bb   Varma, Pradeep ^bb   Chertkow, Howard ^bc   Bergman, Howard ^bc   Hosein, Chris ^bc   Black, Sandra ^bd   Stefanovic, Bojana ^bd   Caldwell, Curtis ^bd   Hsiung, Ging Yuek Robin ^be   Feldman, Howard ^be   Mudge, Benita ^be   Assaly, Michele ^be   Finger, Elizabeth ^bf,ca   Pasternack, Stephen ^bf   Rachisky, Irina ^bf   Trost, Dick ^bf   Kertesz, Andrew ^bf,ca   Bernick, Charles ^bg   Munic, Donna ^bg   Lipowski, Kristine ^bg   Weintraub, Sandra ^bg   Bonakdarpour, Borna ^bg   Kerwin, Diana ^bg   Wu, Chuang Kuo ^bg   Johnson, Nancy ^bg   Sadowsky, Carl ^bh   Villena, Teresa ^bh   Turner, Raymond Scott ^bi   Johnson, Kathleen ^bi   Reynolds, Brigid ^bi   Sperling, Reisa A ^o   Johnson, Keith A ^o   Marshall, Gad ^o   Yesavage, Jerome ^bj   Taylor, Joy L ^bj   Lane, Barton ^bj   Rosen, Allyson ^bj   Tinklenberg, Jared ^bj   Sabbagh, Marwan N ^bk   Belden, Christine M ^bk   Jacobson, Sandra A ^bk   Sirrel, Sherye A ^bk   Kowall, Neil ^bl   Killiany, Ronald ^bl   Budson, Andrew E ^bl   Norbash, Alexander ^bl   Johnson, Patricia Lynn ^bl   Obisesan, Thomas O ^bm   Wolday, Saba ^bm   Allard, Joanne ^bm   Lerner, Alan ^bn   Ogrocki, Paula ^bm   Tatsuoka, Curtis ^bm   Fatica, Parianne ^bm   Fletcher, Evan ⁿ   Maillard, Pauline ⁿ   Olichney, John ⁿ   Carmichael, Owen ⁿ   Kittur, Smita ^bo   Borrie, Michael ^bp   Lee, T Y ^bp   Bartha, Rob ^bp   Johnson, Sterling ^bq   Asthana, Sanjay ^bq   Carlsson, Cynthia M ^bq   Preda, Adrian ^bq   Nguyen, Dana ^bq   Tariot, Pierre ^ag   Burke, Anna ^ag   Trncic, Nadira ^ag   Reeder, Stephanie ^ag   Bates, Vernice ^br   Capote, Horacio ^br   Rainka, Michelle ^br   Scharre, Douglas W ^bs   Kataki, Maria ^bs   Adeli, Anahita ^bs   Zimmerman, Earl A ^bt   Celmins, Dzintra ^bt   Brown, Alice D ^bt   Pearlson, Godfrey D ^bu   Blank, Karen ^bu   Anderson, Karen ^bu   Flashman, Laura A ^bv   Seltzer, Marc ^bv   Hynes, Mary L ^bv   Santulli, Robert B ^bv   Sink, Kaycee M ^bw   Gordineer, Leslie ^bw   Williamson, Jeff D ^bw   Garg, Pradeep ^bw   Watkins, Franklin ^bw   Ott, Brian R ^bx   Querfurth, Henry ^bx   Tremont, Geoffrey ^bx   Salloway, Stephen ^by   Malloy, Paul ^by   Correia, Stephen ^by   Rosen, Howard J ^j   Miller, Bruce L ^j   Perry, David ^j,bh   Mintzer, Jacobo ^bz   Spicer, Kenneth ^bz   Bachman, David ^bz   Pasternak, Stephen ^ca   Rachinsky, Irina ^ca   Rogers, John ^ca   Drost, Dick ^ca   Pomara, Nunzio ^cb   Hernando, Raymundo ^cb   Sarrael, Antero ^cb   Schultz, Susan K ^cc   Boles Ponto, Laura L ^cc   Shim, Hyungsub ^cc   Smith, Karen Ekstam ^cc   Relkin, Norman ^u   Chaing, Gloria ^u   Lin, Michael ^u   Ravdin, Lisa ^u   Smith, Amanda ^cd   Ashok Raj, Balebail ^cd   Fargher, Kristin ^cd   Neylan, Thomas ^j   Grafman, Jordan ^j   Davis, Melissa ^l   Morrison, Rosemary ^l   Hayes, Jacqueline ^j   Finley, Shannon ^j   Friedl, Karl ^cf   Fleischman, Debra ^ar   Arfanakis, Konstantinos ^ar   Doraiswamy, P Murali ^au   James, Olga ^au   Goldstei, Bonnie ^aw   Martin, Kimberly S ^aw   Massoglia, Dino ^bz   Brawman Mintzer, Olga ^bz   Martinez, Walter ^bh   Ros, Howard ^bh   Behan, Kelly ^bi   Johnson, Sterling C ^bq   Fruehling, J Jay ^bq   Harding, Sandra ^bq   Peskind, Elaine R ^e   Petrie, Eric C ^e   Li, Gail ^e   Yesavage, Jerome A ^bj   Furst, Ansgar J ^bj   Chao, Steven ^bj   more..

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b INDIANA UNIVERSITY CENTER FOR AGING RESEARCH   (United States)

^c REGENSTRIEF INSTITUTE   (United States)

^d Prevention and Recovery Center for Early Psychosis   (United States)

^e UNIVERSITY OF WASHINGTON   (United States)

^f MAYO CLINIC   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

^h UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

ⁱ UNIVERSITY OF CALIFORNIA   (United States)

^j UNIVERSITY OF CALIFORNIA   (United States)

^k Department of Biostatistics   (United States)

^l UNIVERSITY OF CALIFORNIA   (United States)

^m UNIVERSITY OF PENNSYLVANIA   (United States)

ⁿ UNIVERSITY OF CALIFORNIA   (United States)

^o HARVARD MEDICAL SCHOOL   (United States)

^p INDIANA UNIVERSITY   (United States)

^q WASHINGTON UNIVERSITY   (United States)

^r SIEMENS AG   (Germany)

^s ALZHEIMER'S ASSOCIATION   (United States)

^t UNIVERSITY OF PITTSBURGH   (United States)

^u Department of Obstetrics Gynecology   (United States)

^v ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^w AD Drug Discovery Foundation   (United States)

^x Acumen Pharmaceuticals   (United States)

^y NORTHWESTERN UNIVERSITY   (United States)

^z NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^aa BROWN UNIVERSITY   (United States)

^ab Eli Lilly   (United States)

^ac UNIVERSITY OF LONDON   (United Kingdom)

^ad UNIVERSITY OF CALIFORNIA   (United States)

^ae UNIVERSITY OF MICHIGAN   (United States)

^af UNIVERSITY OF UTAH   (United States)

^ag BANNER ALZHEIMER S INSTITUTE   (United States)

^ah UNIVERSITY OF PENNSYLVANIA   (United States)

^ai UNIVERSITY OF CALIFORNIA   (United States)

^aj NATIONAL INSTITUTE ON AGING   (United States)

^ak JOHNS HOPKINS UNIVERSITY   (United States)

^al Richard Frank Consulting   (United States)

^am OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^an BAYLOR COLLEGE OF MEDICINE   (United States)

^ao Department of Medicine   (United States)

^ap UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^aq MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^ar RUSH UNIVERSITY MEDICAL CENTER   (United States)

^as Wien Center   (United States)

^at NEW YORK UNIVERSITY   (United States)

^au DUKE UNIVERSITY MEDICAL CENTER   (United States)

^av UNIVERSITY OF KENTUCKY   (United States)

^aw UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^ax UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^ay EMORY UNIVERSITY   (United States)

^az UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

^ba UNIVERSITY OF CALIFORNIA   (United States)

^bb YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^bc MCGILL UNIVERSITY   (Canada)

^bd SUNNYBROOK RESEARCH INSTITUTE   (Canada)

^be UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^bf Montreal Jewish General Hospital ^*  (Canada)

^bg LERNER RESEARCH INSTITUTE   (United States)

^bh Premiere Research Institute (Palm Beach Neurology)   (United States)

^bi GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

^bj STANFORD UNIVERSITY   (United States)

^bk SUN HEALTH RESEARCH INSTITUTE   (United States)

^bl BOSTON UNIVERSITY   (United States)

^bm HOWARD UNIVERSITY   (United States)

^bn CASE WESTERN RESERVE UNIVERSITY   (United States)

^bo Department of Jorge Luis Borges Library   (United States)

^bp Parkwood Hospital   (United States)

^bq UNIVERSITY OF WISCONSIN   (United States)

^br New York Dent Neurologic Institute   (United States)

^bs OHIO STATE UNIVERSITY   (United States)

^bt ALBANY MEDICAL COLLEGE   (United States)

^bu HARTFORD HOSPITAL   (United States)

^bv DARTMOUTH HITCHCOCK MEDICAL CENTER   (United States)

^bw WAKE FOREST UNIVERSITY HEALTH SCIENCES   (United States)

^bx RHODE ISLAND HOSPITAL   (United States)

^by BUTLER HOSPITAL   (United States)

^bz UNIVERSITY OF SOUTH CAROLINA   (United States)

^ca St Joseph's Health Care   (United States)

^cb The Nathan Kline Institute   (United States)

^cc UNIVERSITY OF IOWA   (United States)

^cd UNIVERSITY OF SOUTH FLORIDA   (United States)

^ce Nathan Kline Institute ^*

^cf Psychological Evaluation Posttraumatic Stress Disorder Core   (United States)

^cg USC   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CHOLINERGIC RECEPTOR BLOCKING AGENT; FLUORODEOXYGLUCOSE F 18; GLUCOSE; APOLIPOPROTEIN E4;

AGED; ARTICLE; BRAIN ATROPHY; BRAIN METABOLISM; BRAIN SIZE; COGNITION; COHORT ANALYSIS; CONTROLLED STUDY; CORTICAL THICKNESS (BRAIN); DRUG SAFETY; EXECUTIVE FUNCTION; FEMALE; FOLLOW UP; GLUCOSE METABOLISM; HUMAN; LATERAL BRAIN VENTRICLE; LONGITUDINAL STUDY; MAJOR CLINICAL STUDY; MALE; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; SIDE EFFECT; TEMPORAL CORTEX; ATROPHY; BRAIN; CHEMICALLY INDUCED; COGNITIVE DEFECT; DIAGNOSTIC IMAGING; DRUG EFFECTS; GENETICS; MEMORY DISORDER; METABOLISM; NEUROPSYCHOLOGICAL TEST; PATHOLOGY; PROPORTIONAL HAZARDS MODEL; VERY ELDERLY;

AGED; AGED, 80 AND OVER; APOLIPOPROTEIN E4; ATROPHY; BRAIN; CHOLINERGIC ANTAGONISTS; COGNITION DISORDERS; EXECUTIVE FUNCTION; FEMALE; FLUORODEOXYGLUCOSE F18; HUMANS; MAGNETIC RESONANCE IMAGING; MALE; MEMORY DISORDERS; NEUROPSYCHOLOGICAL TESTS; POSITRON-EMISSION TOMOGRAPHY; PROPORTIONAL HAZARDS MODELS;

EID: 84974603577     PISSN: 21686149     EISSN: None     Source Type: Journal    
DOI: 10.1001/jamaneurol.2016.0580     Document Type: Article

References (49)

1. Ancelin ML, Artero S, Portet F, Dupuy AM, Touchon J, Ritchie K. Non-degenerativemild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ. 2006;332(7539):455-459.
2. Bottiggi KA, Salazar JC, Yu L, et al. Long-term cognitive impact of anticholinergic medications in older adults. Am J Geriatr Psychiatry. 2006;14(11): 980-984.
3. Boustani M, Campbell N, Munger S, Maidment I, Fox C. Impact of anticholinergics on the aging brain: a review and practical application. Aging Health. 2008;4(3):311-320.
4. Cai X, Campbell N, Khan B, Callahan C, Boustani M. Long-term anticholinergic use and the aging brain. Alzheimers Dement. 2013;9(4):377-385.
5. Campbell N, Boustani M, Limbil T, et al. The cognitive impact of anticholinergics: a clinical review. Clin Interv Aging. 2009;4:225-233.
6. Campbell NL, Boustani MA, Lane KA, et al. Use of anticholinergics and the risk of cognitive impairment in an African American population. Neurology. 2010;75(2):152-159.
7. Carrière I, Fourrier-Reglat A, Dartigues JF, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study. Arch Intern Med. 2009;169(14):1317-1324.
8. Fox C, Richardson K, Maidment ID, et al. Anticholinergic medication use and cognitive impairment in the older population: the medical research council cognitive function and ageing study. J AmGeriatr Soc. 2011;59(8):1477-1483.
9. KashyapM, Belleville S, Mulsant BH, et al. Methodological challenges in determining longitudinal associations between anticholinergic drug use and incident cognitive decline. J Am Geriatr Soc. 2014;62(2):336-341.
10. Konishi K, Hori K, Uchida H, et al Adverse effects of anticholinergic activity on cognitive functions in Alzheimer's disease. Psychogeriatrics. 2010;10(1):34-38.
11. Lampela P, Lavikainen P, Garcia-Horsman JA, Bell JS, Huupponen R, Hartikainen S. Anticholinergic drug use, serum anticholinergic activity, and adverse drug events among older people: a population-based study. Drugs Aging. 2013;30(5):321-330.
12. Lechevallier-Michel N, MolimardM, Dartigues JF, Fabrigoule C, Fourrier-Réglat A. Drugswith anticholinergic properties and cognitive performance in the elderly: results from the PAQUID Study.Br J Clin Pharmacol. 2005;59(2):143-151.
13. Shah RC, Janos AL, Kline JE, et al. Cognitive decline in older persons initiating anticholinergic medications. PLoS One. 2013;8(5):e64111.
14. Sittironnarit G, Ames D, Bush AI, et al; AIBL research group. Effects of anticholinergic drugs on cognitive function in older Australians: results from the AIBL study. Dement Geriatr Cogn Disord. 2011;31 (3):173-178.
15. Tannenbaum C, Paquette A, Hilmer S, Holroyd-Leduc J, Carnahan R. A systematic review of amnestic and non-amnestic mild cognitive impairment induced by anticholinergic, antihistamine, GABAergic and opioid drugs. Drugs Aging. 2012;29(8):639-658.
16. Uusvaara J, Pitkala KH, Kautiainen H, Tilvis RS, Strandberg TE. Detailed cognitive function and use of drugs with anticholinergic properties in older people: a community-based cross-sectional study. Drugs Aging. 2013;30(3):177-182.
17. Fox C, Livingston G, Maidment ID, et al. The impact of anticholinergic burden in Alzheimer's dementia-the LASER-AD study. Age Ageing. 2011; 40(6):730-735.
18. Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175(3):401-407.
19. Jessen F, Kaduszkiewicz H, DaerrM, et al. Anticholinergic drug use and risk for dementia: target for dementia prevention. Eur Arch Psychiatry Clin Neurosci. 2010;260(suppl 2):S111-S115.
20. KashyapM, Mulsant BH, Tannenbaum C. Small longitudinal study of serum anticholinergic activity and cognitive change in community-dwelling older adults. Am J Geriatr Psychiatry. 2015;23(3):326-329.
21. Flicker C, Ferris SH, Serby M. Hypersensitivity to scopolamine in the elderly. Psychopharmacology (Berl). 1992;107(2-3):437-441.
22. Molchan SE, Martinez RA, Hill JL, et al. Increased cognitive sensitivity to scopolamine with age and a perspective on the scopolamine model. Brain Res Brain Res Rev. 1992;17(3):215-226.
23. Teipel SJ, Bruno D, Grothe MJ, Nierenberg J, Pomara N. Hippocampus and basal forebrain volumes modulate effects of anticholinergic treatment on delayed recall in healthy older adults. Alzheimers Dement. 2015;1(2):216-219. doi:10.1016/j .dadm.2015.01.007.
24. Jack CR Jr, Bernstein MA, Borowski BJ, et al; Alzheimer's Disease Neuroimaging Initiative. Update on the magnetic resonance imaging core of the Alzheimer's Disease Neuroimaging Initiative. Alzheimers Dement. 2010;6(3):212-220.
25. JagustWJ, Bandy D, Chen K, et al; Alzheimer's Disease Neuroimaging Initiative. The Alzheimer's Disease Neuroimaging Initiative positron emission tomography core. Alzheimers Dement. 2010;6(3): 221-229.
26. Trojanowski JQ, Vandeerstichele H, KoreckaM, et al; Alzheimer's Disease Neuroimaging Initiative. Update on the biomarker core of the Alzheimer's Disease Neuroimaging Initiative subjects. Alzheimers Dement. 2010;6(3):230-238.
27. Petersen RC, Aisen PS, Beckett LA, et al. Alzheimer's Disease Neuroimaging Initiative (ADNI): clinical characterization. Neurology. 2010; 74(3):201-209.
28. Saykin AJ, Shen L, Foroud TM, et al; Alzheimer's Disease Neuroimaging Initiative. Alzheimer's Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: genetics core aims, progress, and plans. Alzheimers Dement. 2010;6(3):265-273.
29. WeinerMW, Aisen PS, Jack CR, Jr, et al; Alzheimer's Disease Neuroimaging Initiative. The Alzheimer's Disease Neuroimaging Initiative: progress report and future plans. Alzheimers Dement. 2010;6 (3):202-211.
30. World Medical Association.World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194. doi:10 .1001/jama.2013.281053.
31. Aging Brain Care. Anticholinergic Cognitive Burden scale: 2012 update. http://www .agingbraincare.org/uploads/products/ACB-scale-legal-size.pdf. Accessed March 24, 2016.
32. Drugs on the Anitcholinergic Burden (ACB) scale. http://www.bmedreport.com/wp-content/uploads/2011/06/Drugs-on-the-Anticholinergic-Burden-ACB-scale.jpg. Accessed March 24, 2016.
33. Anticholinergics and the elderly. Pharmacist's Letter website. http://pharmacistsletter .therapeuticresearch.com/pl/ArticleDD.aspx ?nidchk=1&cs=&s=PL&pt=5&fpt=2&dd=271223& pb=PRL. Accessed March 24, 2016.
34. Risacher SL, Kim S, Nho K, et al; Alzheimer's Disease Neuroimaging Initiative (ADNI). APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern. Alzheimers Dement. 2015;11(12):1417-1429.
35. Risacher SL, Kim S, Shen L, et al; Alzheimer's Disease Neuroimaging Initiative (ADNI). The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment (E-MCI). Front Aging Neurosci. 2013;5:11.
36. Gibbons LE, Carle AC, Mackin RS, et al; Alzheimer's Disease Neuroimaging Initiative. A composite score for executive functioning, validated in Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with baselinemild cognitive impairment. Brain Imaging Behav. 2012;6 (4):517-527.
37. Crane PK, Carle A, Gibbons LE, et al; Alzheimer's Disease Neuroimaging Initiative. Development and assessment of a composite score for memory in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Brain Imaging Behav. 2012;6(4):502-516.
38. Saykin AJ, Wishart HA, Rabin LA, et al. Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI. Neurology. 2006;67(5):834-842.
39. Brett M, Anton JL, Valabregue R, Poline JB. Region of interest analysis using an SPM toolbox [abstract]. Presented at: Eighth International Conference on Functional Mapping of the Human Brain; June 2-6, 2002; Sendai, Japan.
40. Shaw LM, Vanderstichele H, Knapik-Czajka M, et al; Alzheimer's Disease Neuroimaging Initiative. Cerebrospinal fluid biomarker signature in Alzheimer's Disease Neuroimaging Initiative subjects. Ann Neurol. 2009;65(4):403-413.
41. Landau SM, Mintun MA, Joshi AD, et al; Alzheimer's Disease Neuroimaging Initiative. Amyloid deposition, hypometabolism, and longitudinal cognitive decline. Ann Neurol. 2012;72 (4):578-586.
42. Everitt BJ, Robbins TW. Central cholinergic systems and cognition. Annu Rev Psychol. 1997;48: 649-684.
43. Del Pino J, Zeballos G, Anadón MJ, et al. Cadmium-induced cell death of basal forebrain cholinergic neurons mediated by muscarinic M1 receptor blockade, increase in GSK-3β enzyme, β-amyloid and tau protein levels [published online May 31, 2015]. Arch Toxicol. doi:10.1007/s00204- 015-1540-7.
44. Capsoni S, Giannotta S, Stebel M, et al. Ganstigmine and donepezil improve neurodegeneration in AD11 antinerve growth factor transgenicmice. Am J Alzheimers Dis Other Demen. 2004;19(3):153-160.
45. Geula C. Abnormalities of neural circuitry in Alzheimer's disease: hippocampus and cortical cholinergic innervation. Neurology. 1998;51(1) (suppl 1):S18-S29
46. Moreau PH, Cosquer B, Jeltsch H, Cassel JC, Mathis C. Neuroanatomical and behavioral effects of a novel version of the cholinergic immunotoxin mu p75-saporin in mice. Hippocampus. 2008;18(6): 610-622.
47. Paul S, Jeon WK, Bizon JL, Han JS. Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment. Front Aging Neurosci. 2015;7:43.
48. Carroll JC, IbaM, Bangasser DA, et al. Chronic stress exacerbates tau pathology, neurodegeneration, and cognitive performance through a corticotropin-releasing factor receptor-dependent mechanism in a transgenic mouse model of tauopathy. J Neurosci. 2011;31(40): 14436-14449.
49. Resnick SM, Pham DL, Kraut MA, Zonderman AB, Davatzikos C. Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J Neurosci. 2003;23(8):3295-3301.