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Sex Differences of Neuropsychiatric Symptoms in Amyloid-Positive Early-Onset Alzheimer's Disease
Sára Nemes, Department of Neurology, Indiana University School of Medicine, Indianapolis, United States
Paul Aisen, Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, United States
Jeffrey Dage, Department of Neurology, Indiana University School of Medicine, Indianapolis, United States
Ani Eloyan, Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, United States
Tatiana Foroud, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, United States
Lea Grinberg, Department of Pathology and Department of Neurology, University of California - San Francisco, San Francisco, United States
Dustin Hammers, Department of Neurology, Indiana University School of Medicine, Indianapolis, United States
Leonardo Iaccarino, Department of Neurology, University of California - San Francisco, San Francisco, United States
Clifford Jack Jr., Department of Radiology, Mayo Clinic, Rochester, United States
Joel Kramer, Department of Neurology, University of California - San Francisco, San Francisco, United States
Robert Koeppe, Department of Radiology, University of Michigan, Ann Arbor, United States
Walter Kukull, Department of Epidemiology, University of Washington, Seattle, United States
Renaud La Joie, Department of Neurology, University of California – San Francisco, San Francisco, United States
Nidhi Mundada, Department of Neurology, University of California – San Francisco, San Francisco, United States
Melissa Murray, Department of Neuroscience, Mayo Clinic, Jacksonville, United States
Kelly Nudelman, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, United States
Malia Rumbaugh, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, United States
David Soleimani-Meigooni, Department of Neurology, University of California – San Francisco, San Francisco, United States
Arthur Toga, Laboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Los Angeles, United States
Alexandra Touroutoglou, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, United States
Prashanthi Vemuri, Department of Radiology, Mayo Clinic, Rochester, United States
Alireza Atri, Banner Sun Health Research Institute, Sun City, United States
Gregory Day, Department of Neurology, Mayo Clinic, Jacksonville, United States
Ranjan Duara, Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami, United States
Neill Graff-Radford, Department of Neurology, Mayo Clinic, Jacksonville, United States
Lawrence Honig, Taub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, United States
David Jones, Department of Radiology and Department of Neurology, Mayo Clinic, Rochester, United States
Joseph Masdeu, Nantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, United States
Mario Mendez, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, United States
Erik Musiek, Department of Neurology, Washington University in St. Louis, St. Louis, United States
Chiadi Onyike, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, United States
Meghan Riddle, Department of Neurology, Alpert Medical School, Brown University, Providence, United States
Emily Rogalski, Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Feinberg School of Medicine, Northwestern University, Chicago, United States
Steven Salloway, Department of Neurology, Alpert Medical School, Brown University, Providence, United States
Sharon Sha, Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, United States
Raymond Turner, Department of Neurology, Georgetown University, Washington D.C., United States
Thomas Wingo, Department of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, United States
David Wolk, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Maria Carrillo, Medical & Scientific Relations Division, Alzheimer’s Association, Chicago, United States
Bradford Dickerson, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, United States
Gil Rabinovici, Department of Neurology, University of California – San Francisco, San Francisco, United States
Liana Apostolova, Department of Neurology, Indiana University School of Medicine, Indianapolis, United States
Angelina Polsinelli, Department of Neurology, Indiana University School of Medicine, Indianapolis, United States
LEADS Consortium, Indiana University School of Medicine, Indianapolis, United States
Neuropsychiatric symptoms (i.e., depression, apathy, sleep disturbances, appetite changes) are common among people diagnosed with dementia due to Alzheimer’s disease with prevalence between 60-80% (Eikelboom et al. [2021]. Neurolog., 97,e1276). Sex differences in late-onset Alzheimer’s disease (LOAD) suggest females have a higher prevalence and severity of depressive symptoms, delusions, and aberrant motor behaviors while males display more severe apathy (Eikelboom et al. [2022[. Alz. Res. Ther., 14:48). Despite neuropsychiatric symptoms being more prominent in early-onset AD (EOAD) than LOAD, sex differences have not yet been examined. We explored sex differences in neuropsychiatric symptoms in a large sample of individuals with amyloid-positive EOAD.
299 amyloid-positive EOAD participants from the Longitudinal Early-Onset Alzheimer’s Disease Study (LEADS) were included. The Neuropsychiatric Inventory Questionnaire [NPI-Q] – a 12 item informant-report of neuropsychiatric symptoms – and the Geriatric Depression Scale [GDS] – 15 item self-report of depressive symptoms – were completed at study baseline. Behavioral composites of the NPI-Q (Affective, Distress-Tension, Impulse Control, Psychotic), total NPI-Q score, and total GDS score were the main outcome variables. Binary logistic regression examined sex differences in NPI-Q composites. Odds ratio (OR) for the effect of group were estimated with female sex as the reference group adjusting for disease severity (Clinical Dementia Rating-global score). Linear regression adjusting for disease severity compared females and males on the total GDS and NPI-Q scores.
Participants were generally highly educated (M = 15.5, SD = 2.4), predominantly White (91%), and Non-Latino/a (97%). Average age was 58.5 (SD = 4.0) and 51% of the sample was female. Average CDR sum of boxes was 3.8 (SD = 1.8, range = 0-16), indicating very mild dementia. There were no sex differences among demographic variables, APOEƐ4 status, or disease severity (ps > .05). There were no sex differences in NPI-Q composite categories (OR range: 0.70 – 1.16; ps > .05), total GDS total score (p = .13), or NPI-Q total score (p = .59).
In a large sample of individuals with amyloid-positive EOAD, we found no sex differences in presence of neuropsychiatric symptoms. Clinically, these findings suggest that at least in early symptomatic stages of EOAD, identification and monitoring of neuropsychiatric symptoms is not sex-specific and may not require sex-differentiated treatment approaches. However, given that we examined baseline data in only very mild dementia/mild cognitive impairment, it is possible that sex differences may emerge later in the course of the disease (Xing et al. [2015]. Beh. Neuro.) It is also possible that there are differences in severity of neuropsychiatric symptoms between sexes. As LEADS continues to collect data, future research will examine severity of neuropsychiatric symptoms, neuropsychiatric symptoms at later stages of EOAD, and longitudinal changes in neuropsychiatric symptoms in females and males.
Keyword 1: neuropsychological assessment
Keyword 2: dementia - Alzheimer's disease