The association between post-traumatic stress disorder (PTSD) and cognitive impairment: A systematic review of neuroimaging findings.

BACKGROUND: Accumulating evidence suggests that post-traumatic stress disorder (PTSD) may increase the risk of various types of dementia. Despite the large number of studies linking these critical conditions, the underlying mechanisms remain unclear. The past decade has witnessed an exponential increase in interest on brain imaging research to assess the neuroanatomical underpinnings of PTSD. This systematic review provides a critical assessment of available evidence of neuroimaging correlates linking PTSD to a higher risk of dementia. METHODS: The EMBASE, PubMed/MEDLINE, and SCOPUS electronic databases were systematically searched from 1980 to May 22, 2021 for original references on neuroimaging correlates of PTSD and risk of dementia. Literature search, screening of references, methodological quality appraisal of included articles as well as data extractions were independently conducted by at least two investigators. Eligibility criteria included: 1) a clear PTSD definition; 2) a subset of included participants must have developed dementia or cognitive impairment at any time point after the diagnosis of PTSD through any diagnostic criteria; and 3) brain imaging protocols [structural, molecular or functional], including whole-brain morphologic and functional MRI, and PET imaging studies linking PTSD to a higher risk of cognitive impairment/dementia. RESULTS: Overall, seven articles met eligibility criteria, comprising findings from 366 participants with PTSD. Spatially convergent structural abnormalities in individuals with PTSD and co-occurring cognitive dysfunction involved primarily the bilateral frontal (e.g., prefrontal, orbitofrontal, cingulate cortices), temporal (particularly in those with damage to the hippocampi), and parietal (e.g., superior and precuneus) regions. LIMITATIONS: A meta-analysis could not be performed due to heterogeneity and paucity of measurable data in the eligible studies. CONCLUSIONS: Our systematic review provides putative neuroimaging correlates associated with PTSD and co-occurring dementia/cognitive impairment particularly involving the hippocampi. Further research examining neuroimaging features linking PTSD to dementia are clearly an unmet need of the field. Future imaging studies should provide a better control for relevant confounders, such as the selection of more homogeneous samples (e.g., age, race, education), a proper control for co-occurring disorders (e.g., co-occurring major depressive and anxiety disorders) as well as the putative effects of psychotropic medication use. Furthermore, prospective studies examining imaging biomarkers associated with a higher rate of conversion from PTSD to dementia could aid in the stratification of people with PTSD at higher risk for developing dementia for whom putative preventative interventions could be especially beneficial.

Neuroimaging assessment of pediatric cerebral changes associated with SARS-CoV-2 infection during pregnancy.

Background: SARS-CoV-2 infection and perinatal neurologic outcomes are still not fully understood. However, there is recent evidence of white matter disease and impaired neurodevelopment in newborns following maternal SARS-CoV-2 infection. These appear to occur as a consequence of both direct viral effects and a systemic inflammatory response, with glial cell/myelin involvement and regional hypoxia/microvascular dysfunction. We sought to characterize the consequences of maternal and fetal inflammatory states in the central nervous system of newborns following maternal SARS-CoV-2 infection. Methods: We conducted a longitudinal prospective cohort study from June 2020 to December 2021, with follow-up of newborns born to mothers exposed or not exposed to SARS-CoV-2 infection during pregnancy. Brain analysis included data from cranial ultrasound scans (CUS) with grayscale, Doppler studies (color and spectral), and ultrasound-based brain elastography (shear-wave mode) in specific regions of interest (ROIs): deep white matter, superficial white matter, corpus callosum, basal ganglia, and cortical gray matter. Brain elastography was used to estimate brain parenchymal stiffness, which is an indirect quantifier of cerebral myelin tissue content. Results: A total of 219 single-pregnancy children were enrolled, including 201 born to mothers exposed to SARS-CoV-2 infection and 18 from unexposed controls. A neuroimaging evaluation was performed at 6 months of adjusted chronological age and revealed 18 grayscale and 21 Doppler abnormalities. Predominant findings were hyperechogenicity of deep brain white matter and basal ganglia (caudate nuclei/thalamus) and a reduction in the resistance and pulsatility indices of intracranial arterial flow. The anterior brain circulation (middle cerebral and pericallosal arteries) displayed a wider range of flow variation than the posterior circulation (basilar artery). Shear-wave US elastography analysis showed a reduction in stiffness values in the SARS-CoV-2 exposed group in all analyzed regions of interest, especially in the deep white matter elasticity coefficients (3.98 ± 0.62) compared to the control group (7.76 ± 0.77); p-value < 0.001. Conclusion: This study further characterizes pediatric structural encephalic changes associated with SARS-CoV-2 infection during pregnancy. The maternal infection has been shown to be related to cerebral deep white matter predominant involvement, with regional hyperechogenicity and reduction of elasticity coefficients, suggesting zonal impairment of myelin content. Morphologic findings may be subtle, and functional studies such as Doppler and elastography may be valuable tools to more accurately identify infants at risk of neurologic damage.