Altered Functional Connectivity and Amyloid Deposition in PTSD-Associated Cognitive Impairment.

Abstract

Background and purpose: PTSD has been linked to an increased risk of cognitive impairment and dementia, with neuroinflammation, metabolic dysfunction, and neuropathological markers such as beta-amyloid and tau implicated as potential mechanisms. However, the roles of altered functional connectivity and amyloid deposition as biomarkers in the progression of cognitive impairment among PTSD patients remain unclear, with limited and often conflicting evidence from existing neuroimaging studies. This study examines these neuroimaging markers in PTSD patients with and without cognitive impairment to better understand the neurobiological pathways contributing to cognitive decline in PTSD.

Materials and methods: Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Department of Defense (DOD) ADNI databases. A cohort of 178 age-matched male subjects was divided into four groups: PTSD with cognitive impairment (CI) (PTSD-CI); PTSD and cognitively normal (CN) (PTSD-CN); non-PTSD (NPTSD with CI (NPTSD-CI); and NPTSD and CN (NPTSD-CN). All subjects underwent resting-state functional MRI and amyloid PET imaging, with PTSD diagnosis and CI confirmed through clinical assessments. Functional connectivity was analyzed using the CONN Toolbox, and amyloid burden was quantified via standardized uptake value ratios. Analyses controlled for demographic and genetic factors, including age, education, APOE4 status, and depression.

Results: Compared to the NPTSD-CN group, the PTSD-CI group showed significantly increased amyloid uptake in the temporal and parietal lobes, with corresponding functional connectivity increase between the bilateral temporal lobes and parietal operculum. In contrast, PTSD-CN patients exhibited no significant amyloid increase but showed increased connectivity between the salience network, postcentral gyri and sensorimotor areas, and decreased connectivity between the sensorimotor network and anterior cingulate cortex. These distinct patterns suggest differing neurobiological profiles between PTSD-CI and PTSD-CN patients.

Conclusions: The findings suggest that elevated amyloid and altered connectivity patterns are associated with CI in PTSD, particularly in the temporal and parietal regions. In contrast, PTSD without cognitive decline was associated with functional connectivity changes in salience and sensorimotor networks but no increased amyloid deposition. This study underscores the importance of neuroimaging biomarkers in understanding PTSD-related cognitive decline and suggests avenues for further investigation into the mechanistic pathways involved.

Abbreviations: ACC = anterior division of the cingulate gyrus; ADAS-Cog = Alzheimer's Disease Assessment Scale-Cognitive; CAPS = Clinician-Administered PTSD Scale; PTSD = post-traumatic stress disorder; CI = cognitively impaired; CN = cognitively normal; ECog = Everyday Cognition; GDS = Geriatric Depression Scale; MoCA = Montreal Cognitive Assessment; NPTSD = non-PTSD.