Despite having severe Alzheimer disease pathology, some individuals remain cognitively asymptomatic (cASYM). To explore noncognitive manifestations in these cASYM individuals, we aim to investigate the prevalence and pathologic substrates of psychosis.
Data were obtained from the National Alzheimer’s Coordinating Center. The Neuropsychiatric Inventory Questionnaire, quick version was used to evaluate presence of psychosis. Subjects with Mini-Mental Status Examination score of ≥24 with frequent neuritic plaques (NPs) were defined as NPcASYM, and those with Braak and Braak stage of neurofibrillary tangles of V/VI were defined as NTcASYM (both groups collectively designated cASYM). Logistic regression analysis was used to examine the association between NP and neurofibrillary tangle severity and psychosis accounting for potential confounders.
We identified 667 subjects with Mini-Mental Status Examination score of ≥24, of which 137 were NPcASYM and 96 were NTcASYM. NPcASYM were at significantly higher risk of having psychosis compared with those with moderate or sparse/no NP (odds ratio, 2.47; 95% confidence interval, 1.54-3.96). NTcASYM were also at higher risk compared with those with Braak and Braak stage I to IV, but the association explained by the effect of Lewy body pathology and microinfarcts.
The load of NP may be an important substrate of psychosis in individuals who show no gross cognitive symptoms.
*Keenan Research Centre for Biomedical Research, the Li Ka Shing Knowledge Institute
Divisions of ∥Neurosurgery
**Pathology, St. Michael’s Hospital
†Institute of Medical Sciences
‡Institute of Biomaterials and Biomedical Engineering
Departments of §Surgery, Division of Neurosurgery, Faculty of Medicine
¶Psychiatry, Faculty of Medicine
#Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Supported by the Canadian Institutes of Health Research (CIHR) (Grant number 313912). The NACC data are contributed by the NIA funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Steven Ferris, PhD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016570 (PI Marie-Francoise Chesselet, MD, PhD), P50 AG005131 (PI Douglas Galasko, MD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P50 AG005136 (PI Thomas Montine, MD, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), and P50 AG047270 (PI Stephen Strittmatter, MD, PhD).
The authors declare no conflicts of interest.
Reprints: David G. Munoz, MD, Department of Laboratory Medicine, Room 2-097 CC Wing, St. Michael’s Hospital, 30 Bond Street, Toronto, ON, Canada, M5B 1W8 (e-mail: MunozD@smh.ca).
Received August 29, 2017
Accepted January 23, 2018