JAMA Network Open: Neuropsychiatric Symptoms and Microglial Activation in Patients with Alzheimer Disease

Neuropsychiatric symptoms including irritability, nighttime disturbances, and agitation are highly prevalent in Alzheimer’s disease and related dementias. Although neuropsychiatric symptoms are clinically well characterized in individuals with Alzheimer’s, scientists have more to learn regarding these symptoms’ neurobiological underpinnings. Investigators including Cristiano Schaffer Aguzzoli, MD (former Pitt Psychiatry postdoctoral associate; currently: InsCer, Brazil), Pâmela Lukasewicz Ferreira, PhD (Research Assistant Professor of Psychiatry); Bruna Bellaver, PhD (Research Assistant Professor of Psychiatry); Firoza Lussier, MSc (Research Program Administrator); Douglas Leffa, MD, PhD (PGY2 psychiatry resident); Ann Cohen, PhD (Associate Professor of Psychiatry); Dana Tudorascu, PhD (Associate Professor of Psychiatry and Biostatistics); William Klunk, MD, PhD (Distinguished Professor Emeritus of Psychiatry); Victor Villemagne, MD (Professor of Psychiatry); Thomas Karikari, PhD (Assistant Professor of Psychiatry); and Tharick Pascoal, MD, PhD (Associate Professor of Psychiatry and Neurology), from the University of Pittsburgh, studied the association between neuropsychiatric symptoms and glial markers (microglial activation and astrocyte reactivity), in individuals with Alzheimer’s.

The team conducted a cross-sectional study of 70 cognitively unimpaired and 39 cognitively impaired individuals who underwent neuropsychological assessment, as well as imaging for microglial activation, amyloid-β, and tau tangles. Participants were selected from the Translational Biomarkers in Aging and Dementia cohort at McGill University.

Results from the study revealed that microglial activation is associated with neuropsychiatric symptoms in individuals across the Alzheimer’s disease continuum, and that irritability, nighttime disturbances, and agitation are the neuropsychiatric symptoms most likely to be associated with microglial activation.

“Our results suggest that microglia-targeted therapies could be tested in future clinical trials to mitigate neuropsychiatric symptoms in patients with dementia,” said Dr. Pascoal, the study’s senior author.

Neuropsychiatric Symptoms and Microglial Activation in Patients with Alzheimer Disease
Aguzzoli CS, Ferreira PCL, Povala G, Ferrari-Souza JP, Bellaver B, Katz CS, Zalzale H, Lussier FZ, Rohden F, Abbas S, Leffa DT, Medeiros MS, Therriault J, Benedet A, Tissot C, Servaes S, Rahmouni N, Macedo AC, Bezgin G, Kang MS, Stevenson J, Pallen V, Cohen A, Lopez OL, Tudorascu DL, Klunk WE, Villemagne VL, Soucy JP, Zimmer ER, Schilling LP, Karikari TK, Ashton NJ, Zetterberg H, Blennow K, Gauthier S, Valcour V, Miller BL, Rosa-Neto P, Pascoal TA.
JAMA Network Open. 2023;6(11):e2345175. doi:10.1001/jamanetworkopen.2023.45175