Dr. Kelsey R. Thomas, PhD, VA San Diego Healthcare System and the University of California, San Diego
SAN DIEGO — While cognitive decline in older people often raises suspicion of early Alzheimer’s disease, a new VA study underscores the importance of considering how factors beyond Alzheimer’s—including post-traumatic stress disorder (PTSD), pain and sleep difficulties—might also impact cognition in older veterans.
“Much of the work on early detection of Alzheimer’s disease is done in cohorts of older adults who really don’t represent the complex medical and psychiatric conditions that tend to be more prominent in older veterans,” explained Kelsey R. Thomas, PhD, lead researcher of the study, which was published in the Journal of Alzheimer’s Disease.
For that reason, Thomas, who is with the VA San Diego Healthcare System and the University of California, San Diego, sought to examine groups, based on objective and subjective cognition, as well as amyloid PET imaging, to determine whether psychiatric and health factors were more associated with certain cognitive deficits and amyloid profiles.
To do that, the study team used data from 228 predominantly male Vietnam-era veterans from the DoD’s Alzheimer’s Disease Neuroimaging Initiative post-traumatic stress disorder—a longitudinal multicenter study designed to develop clinical, imaging, genetic and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease. Thomas and her colleagues conducted a cluster analysis of neuropsychological measures, subjective cognitive decline and amyloid burden, as measured by the buildup of abnormal amyloid protein in the brain.
They then compared subgroups on clinical characteristics, biomarkers and longitudinal change in functioning and global cognition. Cluster-derived subgroups were compared on baseline characteristics as well as 1-year changes in everyday functioning and global cognition.1
The cluster analysis identified three groups. At baseline, the largest group, which consisted of 128 veterans, had average-to-above average cognition with low amyloid burden. The middle group, with 72 veterans, showed difficulties with memory and language but had an average risk of Alzheimer’s disease. The middle group also had the highest rates of PTSD, pain and sleep difficulties. The smallest group, with 28 members, had the lowest attention/executive functioning, slightly low memory and language, elevated amyloid and the worst Alzheimer’s disease biomarkers. At one year, the last group also showed the fastest rates of decline in both of everyday functioning and cognition.
“It is very likely that the veterans in this group had a biological Alzheimer’s disease or a pre-clinical Alzheimer’s disease,” Thomas pointed out. She said it was surprising that the most prominent issue for the group was attention and executive function, since memory decline is typically the primary symptom of early Alzheimer’s.
“We are speculating this could represent a unique presentation of biological Alzheimer’s in veterans, who tend to have higher rates of co-occurring psychiatric symptoms, TBI histories and vascular risk factors,” she said, adding that nearly 65% of the sample had hypertension and much higher rates of diabetes than nonveterans.”
“It is possible that some of these co-occurring conditions could interact with Alzheimer’s disease pathology to show more of an effect on executive function, whereas memory is the most prominent symptom in other populations,” Thomas added.
Screenings Might Overlook Some Veterans
The findings suggested that certain Alzheimer’s disease screenings focusing on memory difficulties might overlook older veterans at risk. Such tests also might lead clinicians to suspect Alzheimer’s in veterans whose difficulties with memory are related to other factors.
“I think it just shows the importance of contextualizing the cognitive difficulties,” Thomas advised. “While it does take a bit more, it is probably best done as a kind of multidisciplinary approach that include some psychologic test as well as a more thorough workup of psychiatric health and other conditions be really deciding on a diagnosis and treatment plan.”
She noted that the study highlights the need for an individualized approach to veterans based on factors that may contribute to their cognitive performance. “Things like PTSD, pain and sleep should not be overlooked and are potentially treatable,” she said. “So, even if we think someone does have Alzheimer’s disease, we should not ignore these other factors, because we may see cognitive improvement if we can help with some of these other factors.”
- Thomas, K. R., Clark, A. L., Weigand, A. J., Edwards, L., et al. (2024). Cognition and Amyloid-β in Older Veterans: Characterization and Longitudinal Outcomes of Data-Derived Phenotypes. Journal of Alzheimer’s Disease: JAD, 99(1), 417–427. https://doi.org/10.3233/JAD-240077