Neuropathologic Correlates of Psychiatric Symptoms in Alzheimer’s Disease

Article type: Research Article

Authors: Ehrenberg, Alexander J.^{a; b} | Suemoto, Claudia K.^c | França Resende, Elisa de Paula^{a; d} | Petersen, Cathrine^a | Leite, Renata Elaine Paraizo^c | Rodriguez, Roberta Diehl^c | Ferretti-Rebustini, Renata Eloah de Lucena^{c; e} | You, Michelle^a | Oh, Jun^a | Nitrini, Ricardo^c | Pasqualucci, Carlos Augusto^c | Jacob-Filho, Wilson^c | Kramer, Joel H.^a | Gatchel, Jennifer R.^f | Grinberg, Lea T.^{a; c; d; *}

Affiliations: [a] Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA | [b] Department of Integrative Biology, University of California, Berkeley, Berkeley, CA, USA | [c] University of São Paulo Medical School, São Paulo, Brazil | [d] Global Brain Health Institute, University of California, San Francisco, San Francisco, CA, USA | [e] University of São Paulo, School of Nursing, São Paulo, Brazil | [f] Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Correspondence: [*] Correspondence to: Lea T. Grinberg, MD, PhD, 675 Nelson Rising Lane, San Francisco, CA 94158, USA. Tel.: +1 415 502 7174; E-mail: lea.grinberg@ucsf.edu.

Abstract: Clarifying the relationships between neuropsychiatric symptoms and Alzheimer’s disease (AD)-related pathology may open avenues for effective treatments. Here, we investigate the odds of developing neuropsychiatric symptoms across increasing burdens of neurofibrillary tangle and amyloid-β pathology. Participants who passed away between 2004 and 2014 underwent comprehensive neuropathologic evaluation at the Biobank for Aging Studies from the Faculty of Medicine at the University of São Paulo. Postmortem interviews with reliable informants were used to collect information regarding neuropsychiatric and cognitive status. Of 1,092 cases collected, those with any non-Alzheimer pathology were excluded, bringing the cohort to 455 cases. Braak staging was used to evaluate neurofibrillary tangle burden, and the CERAD neuropathology score was used to evaluate amyloid-β burden. The 12-item neuropsychiatric inventory was used to evaluate neuropsychiatric symptoms and CDR-SOB score was used to evaluate dementia status. In Braak I/II, significantly increased odds were detected for agitation, anxiety, appetite changes, depression, and sleep disturbances, compared to controls. Increased odds of agitation continue into Braak III/IV. Braak V/VI is associated with higher odds for delusions. No increased odds for neuropsychiatric symptoms were found to correlate with amyloid-β pathology. Increased odds of neuropsychiatric symptoms are associated with early neurofibrillary tangle pathology, suggesting that subcortical neurofibrillary tangle accumulation with minimal cortical pathology is sufficient to impact quality of life and that neuropsychiatric symptoms are a manifestation of AD biological processes.

Keywords: Alzheimer’s disease, amyloid plaques, anxiety, appetite behavior, depression, neurofibrillary tangles, neuropathology, neuropsychiatry, sleep, tau protein

DOI: 10.3233/JAD-180688

Journal: Journal of Alzheimer's Disease, vol. 66, no. 1, pp. 115-126, 2018