Diabetes is Not Associated with Alzheimer’s Disease Neuropathology

Article type: Research Article

Authors: dos Santos Matioli, Maria Niures Pimentel^{a; 1; *} | Suemoto, Claudia Kimie^{b; c; 1; *} | Rodriguez, Roberta Diehl^{a; c} | Farias, Daniela Souza^c | da Silva, Magnólia Moreira^c | Leite, Renata Elaine Paraizo^{b; c} | Ferretti-Rebustini, Renata Eloah Lucena^c | Farfel, José Marcelo^{b; c} | Pasqualucci, Carlos Augusto^c | Jacob Filho, Wilson^{b; c} | Arvanitakis, Zoe^d | Naslavsky, Michel Satya^e | Zatz, Mayana^e | Grinberg, Lea Tenenholz^{c; f} | Nitrini, Ricardo^{a; c}

Affiliations: [a] Department of Neurology, University of São Paulo Medical School, São Paulo, Brazil | [b] Division of Geriatrics, University of São Paulo Medical School, São Paulo, Brazil | [c] Brain Bank of the Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil | [d] Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA | [e] Human Genome and Stem Cell Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil | [f] Department of Neurology, University of California, San Francisco, CA, USA

Correspondence: [*] Correspondence to: Claudia Kimie Suemoto and Maria Niures Pimentel dos Santos Matioli, Avenida Doutor Arnaldo, 455, room 1353, São Paulo, SP 01246-903, Brazil. Tel./Fax: +55 1130618249; E-mails: [email protected] (C.K. Suemoto); [email protected] (M.N.P. dos Santos Matioli).

Note: [1] These authors contributed equally to this work.

Abstract: Background:Previous evidence linking diabetes to Alzheimer’s disease (AD) neuropathology is mixed and scant data are available from low- and middle-income countries. Objective:To investigate the association between diabetes and AD neuropathology in a large autopsy study of older Brazilian adults. Methods:In this cross-sectional study, diabetes was defined by diagnosis during life or use of antidiabetic medication. A standardized neuropathological examination was performed using immunohistochemistry. The associations of diabetes with Consortium to Establish and Registry for Alzheimer Disease (CERAD) scores for neuritic plaques and Braak-Braak (BB) scores for neurofibrillary tangles were investigated using multivariable ordinal logistic regression. We investigated effect modification of education, race, and APOE on these associations. Results:Among 1,037 subjects (mean age = 74.4±11.5 y; mean education = 4.0±3.7 y; 48% male, 61% White), diabetes was present in 279 subjects. Diabetes was not associated with BB (OR = 1.12, 95% CI = 0.81–1.54, p = 0.48) or with CERAD (OR = 0.97, 95% CI = 0.68–1.38, p = 0.86) scores on analyses adjusted for sociodemographic and clinical variables. We observed effect modification by the APOE allele ɛ4 on the association between diabetes mellitus and BB scores. Conclusion:No evidence of an association between diabetes and AD neuropathology was found in a large sample of Brazilians; however, certain subgroups, such as APOE allele ɛ4 carriers, had higher odds of accumulation of neurofibrillary tangles.

Keywords: Alzheimer’s disease, autopsy study, dementia, diabetes mellitus, neuropathology

DOI: 10.3233/JAD-170179

Journal: Journal of Alzheimer's Disease, vol. 60, no. 3, pp. 1035-1043, 2017