The Australian Imaging, Biomarkers and Lifestyle study of ageing (AIBL) Veterans study - Post traumatic stress disorder and risk of Alzheimer's disease

Abstract

Background Epidemiological studies have suggested an association between posttraumatic stress disorder (PTSD) and Alzheimer’s dementia in Vietnam veterans. These studies, however, did not use biomarkers of Alzheimer’s disease (AD) to either confirm the diagnosis or assess the relative prevalence of AD pathology when investigating the risk of dementia in PTSD. Aim This study aimed at testing the hypothesis that Vietnam veterans with combat PTSD have an increased risk for Alzheimer’s disease in comparison with veteran controls as measured by biomarkers such as amyloid-beta and tau retention in the brain and regional hypometabolism and atrophy. Method Vietnam veterans with a history of PTSD as defined by the Clinicians-Administered PTSD scale (CAPS) score of 40 or above and veteran control subjects as defined by CAPS score of 30 or below and with no current clinical evidence of dementia participated in the study. Outcome measurements were amyloid-beta and tau deposition and regional brain metabolism and volumetry. Amyloid-beta and tau burden was estimated by the Specific Uptake Value Ratio (SUVR) of 18F-florbetaben, and 18F-AV-1451 respectively. 18F-fluorodeoxyglucose positron emission tomographic (PET) scan measured regional brain metabolism, and 3-Tesla T1 MP-RAGE Magnetic Resonance Imaging (MRI) estimated regional volumetry. Comprehensive neuropsychological battery measured cognitive function. Results Between March 2014 and June 2017, 83 male Vietnam Veterans (controls, n=30, CAPS=4; lifetime PTSD, n=53, CAPS=73.95; lifetime and current PTSD, n=30, CPAS=52.50) completed the assessments. There was no significant difference between the two groups in the uptake of 18F-florbetaben, 18F-AV-1451 or 18F-fluorodeoxyglucose, or regional brain volumetry. The rate of apolipoprotein E e4 allele was not significantly different between the groups. Compared with control veterans, the PTSD participants had a significantly lower level of education, predicted premorbid Intelligent Quotient (IQ), and total intracranial volume and higher depression rating score. The Montreal Cognitive Assessment score was significantly lower in the PTSD group than in controls. The group differences in Montreal Cognitive Assessment did not remain, however, when adjusted for premorbid IQ or depression in a multilinear regression model analysis. Conclusions Posttraumatic stress disorder is not associated with an increased prevalence of biomarkers of Alzheimer’s disease. The proxy measures of cognitive reserve, a factor that may delay the onset of Alzheimer’s dementia, were relatively low in subjects with PTSD, and this may explain the previously reported higher incidence of dementia in subjects with PTSD compared to age-matched controls.