Recent Research in Alzheimer’s & Dementia
Recent research published in Alzheimer's & Dementia from Anne Cohen, PhD (Associate Professor of Psychiatry), and Victor Villemagne, MD (Levidow-Pittsburgh Foundation Chair in Alzheimer's Disease and Dementia Disorders and Professor of Psychiatry), advance our understanding of Alzheimer’s disease pathology and progression.
Progression to Alzheimer's disease is hypothesized to begin with a preclinical phase of normal cognition that can precede dementia diagnosis by up to 20 years. The continuum of Alzheimer's disease can span from clinically asymptomatic to severely impaired stages. Higher daily physical activity levels have been associated with slower cognitive decline, a lower risk of Alzheimer’s and related dementias, and less amyloid and tau burden. However, self-reported temporal patterns of physical activity can be inaccurate, particularly among older adults.
Scientists led by Dr. Cohen, along with lead author Yurun Cai, PhD (Assistant Professor of Health & Community Systems), developed an activity complexity measure for older adults that quantifies the complexity of daily activities (e.g., more diverse and non-repetitive patterns of movement), and examined whether this measure was associated with cognitive status and Alzheimer's disease pathology. Results of the study suggested that relative to conventional volume or intensity measures of activity, a low complexity of daytime activities is associated with poorer cognition. In addition, more stable activity patterns across days may be linked to less Alzheimer's disease-related biomarker burden.
Cai Y, Snitz B, Cohen A.
Alzheimer's & Dementia. 2026; 22:e71181. https://doi.org/10.1002/alz.71181
2-Aminobutyrate Mediates the Impact of Air Pollution on Blood Biomarkers of Alzheimer's Disease
Early biomarkers of Alzheimer's disease, such as plasma phosphorylated tau and amyloid beta (Aβ), and neurodegeneration may be associated with altered metabolic profiles alterations in mid-life. Metabolic alterations and profiles are shaped by both lifestyle factors and environmental exposures. Recent data suggest that long-term exposure to air pollution may be linked to Alzheimer's disease pathology and dementia.
A team of scientists led by Dr. Cohen and including lead author Anum Saeed, MD (Assistant Professor of Medicine), as well as Dr. Villemagne, Tharick Pascoal, MD, PhD (Associate Professor of Psychiatry and Neurology), and Thomas Karikari, PhD (Associate Professor of Psychiatry and Clinical and Translational Science), from Pitt Psychiatry, examined the association of mid-life metabolic markers with late-life Alzheimer's disease plasma biomarkers, then evaluated their role as mediators of air pollution on Alzheimer's disease risk. The team found evidence of a metabolic mediator between air pollution and Alzheimer's disease risk, with seven mid-life metabolites inversely linked to late-life plasma phosphorylated tau 181 (an Alzheimer’s disease biomarker).
Saeed A, McKennan C, Clougherty JE, Zhou P, Tripathy S, Kinnee EJ, Duan J, Kip K, Zeng X, Villemagne V, Pascoal T, Mapstone M, Whitsel EA, Lopez OI, Ballantyne C, Karikari TK, Yu B, Reis S, Cohen A.
Alzheimer's & Dementia. 2026; 22:e71388. https://doi.org/10.1002/alz.71388
Complex Interplay of Astrogliosis and Pathology in Preclinical Alzheimer's Disease
Neuroinflammation is a recent inclusion in the revised National Institute on Aging and the Alzheimer's Association guidelines for diagnosing and staging Alzheimer's disease. This update necessitates further investigation of neuroinflammation’s role in the Alzheimer's development pathway. Reactive astrogliosis is a diverse spectrum of molecular, morphological, and functional changes in astrocytes as they respond to central nervous system injury, and is an early neuroinflammatory event in several neurodegenerative conditions including Alzheimer's disease.
Investigators led by Dr. Villemagne, along with lead author Alexandra Gogola (Senior Medical Data Scientist, Department of Radiology PET Research Center), investigated the impact of reactive astrogliosis in early stages of Alzheimer's disease development by directly comparing indices of regional SMBT-1 PET and plasma glial fibrillary acidic protein (GFAP) with respect to early Alzheimer's disease pathology and symptoms.
The investigators found that plasma GFAP and SMBT-1 were not associated in cognitively unimpaired individuals and were only associated when cognitive impairment was present. Astrogliosis assessed by SMBT-1 acts as an attenuating moderator between Aβ and tau and memory impairment, whereas plasma GFAP-assessed astrogliosis does not. The findings indicate that SMBT-1 and plasma GFAP are not necessarily reflecting the same type of astrogliosis, with regional SMBT-1 as a potential earlier indicator.
Minjie Wu, PhD (Assistant Professor of Psychiatry), Howard Aizenstein, MD, PhD (Charles F. Reynolds III and Ellen G. Detlefsen Endowed Chair in Geriatric Psychiatry and Professor of Psychiatry, Bioengineering and Clinical and Translational Science), Dr. Karikari, and Dr. Cohen, from Pitt Psychiatry, are co-authors on the paper.
Gogola A, Minhas D, Lopresti B, Snitz B, Reese AC, Matan C, Wu M, Zeng X, Saeed A, Reis S, Aizenstein H, Ikonomovic MD, Lopez O, Karikari T, Cohen A, Villemagne V.
Alzheimer’s & Dementia. 2026; 22:e71520. https://doi.org/10.1002/alz.71520