Pitt Psychiatry Research Published in Alzheimer's & Dementia
Pitt Psychiatry investigators have recently published studies in Alzheimer's & Dementia. Below is a summary of recent original research on neural factors underlying cognitive and depressive symptoms in late life, sleep and rest–activity rhythms across different cognitive aging pathways, and the association between attention-deficit/hyperactivity disorder and Alzheimer’s disease.
Pitt Psychiatry investigators sought to identify shared versus distinct neural factors underlying cognitive and depressive symptoms in late life, and investigated resting-state brain connectivity correlates of cognitive and depressive symptoms in older adults using clinical, blood, and neuroimaging data.
The scientists found that altered brain connectivity and increased white matter damage are linked to both cognitive decline and depressive symptoms in older adults. Key shared brain regions included the amygdala, hippocampus, and ventral tegmental area that may be affected in late life. These findings suggest overlapping neural pathways for late-life depression and cognitive impairment, pointing to possible targets for treatment.
Kolobaric A, Andreescu C, Gerlach AR, Jašarević E, Aizenstein H, Pascoal TA, Ferreira PCL, Bellaver B, Hong CH, Roh HW, Cho YH, Hong S, Nam YJ, Park B, Lee DY, Kim N, Choi JW, Son SJ, Karim HT.
Alzheimer's & Dementia 2025. Volume 21, Issue 3. March 2025. 21:e14493. https://doi.org/10.1002/alz.14493
Sleep Trajectories Across Three Cognitive-Aging Pathways in Community Older Adults
Alterations in sleep and circadian rest–activity rhythms are clinical features of Alzheimer's disease and related dementias. However, normative age-related changes in sleep are not well-delineated from sleep changes that may arise from neurodegenerative processes. A multidisciplinary team of sleep-health scientists conducted a community-based longitudinal study to characterize trajectories of modifiable aspects of sleep health (such as sleep duration, timing, and regularity) across different cognitive aging pathways.
Compared to individuals who remain cognitively healthy over time, those who eventually develop dementia demonstrated lower sleep duration prior to the onset of cognitive impairment. However, sleep duration increased over time and following cognitive diagnoses in the dementia pathway, such that individuals with dementia slept on average one hour longer than individuals who remained cognitively unimpaired. The study also found that sleep and circadian rhythms became more irregular over time across all pathways, but that these changes occurred more rapidly following dementia diagnosis. Notably, sleep timing shifted earlier over time regardless of cognitive aging trajectory, which may suggest that it is more closely related to aging than cognitive health. Overall, these findings suggest that while both short and long sleep duration appear to be associated with dementia, short sleep presents earlier in the pathway and may be a risk factor for future cognitive decline and dementia while longer sleep following dementia may reflect more advanced neurodegeneration.
Zaheed AB, Tapia AL, Oryshkewych N, Wheeler BJ, Butters MA, Buysse DJ, Leng Y, Barnes LL, Lim A, Yu L, Soehner AM, Wallace ML.
Alzheimer's & Dementia 2025. Volume 21, Issue 5. May 2025. 21:e70159. https://doi.org/10.1002/alz.70159
Pitt Psychiatry investigators conducted a study aimed at determining whether the attention-deficit/hyperactivity disorder (ADHD) polygenic risk score—a well-established biomarker of ADHD—is linked to cognitive dysfunction and higher biomarker levels of Alzheimer’s disease pathology in individuals with mild cognitive impairment and dementia. The scientists used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a multicenter study aimed at developing clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease.
They observed lower executive function in individuals with high ADHD polygenic risk score for both mild cognitive impairment and dementia participants. Higher levels of cerebrospinal fluid phosphorylated tau, but not Aβ, were observed in dementia participants with higher ADHD polygenic risk score. Increased ADHD polygenic risk score was associated with glucose hypometabolism in the frontal and parietal cortices.
Leffa DT, Povala G, Bellaver B, Ferrari-Souza JP, Ferreira PCL, Lussier FZ, Aguzzoli CS, Soares C, Zalzale H, Rohden F, Bauer-Negrini G, Abbas S, Schneider M, Therriault J, Lopez OL, Villemagne VL, Klunk WE, Tudorascu DL , Cohen AD, Rosa-Neto P, Zimmer ER, Karikari TK, Rohde LA, Molina BSG, Pascoal TA, the Alzheimer's Disease Neuroimaging Initiative.
Alzheimer's & Dementia 2025. Volume 21, Issue 2. February 2025. DOI: 10.1002/alz.70003