Association between metabolic syndrome and white matter integrity in young and mid-age post-9/11 adult Veterans.

Metabolic syndrome has been associated with reduced brain white matter integrity in older individuals. However, less is known about how metabolic syndrome might impact white matter integrity in younger populations. This study examined metabolic syndrome-related global and regional white matter integrity differences in a sample of 537 post-9/11 Veterans. Metabolic syndrome was defined as ≥3 factors of: increased waist circumference, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension, and high fasting glucose. T1 and diffusion weighted 3 T MRI scans were processed using the FreeSurfer image analysis suite and FSL Diffusion Toolbox. Atlas-based regions of interest were determined from a combination of the Johns Hopkins University atlas and a Tract-Based Spatial Statistics-based FreeSurfer WMPARC white matter skeleton atlas. Analyses revealed individuals with metabolic syndrome (n = 132) had significantly lower global fractional anisotropy than those without metabolic syndrome (n = 405), and lower high-density lipoprotein cholesterol levels was the only metabolic syndrome factor significantly related to lower global fractional anisotropy levels. Lobe-specific analyses revealed individuals with metabolic syndrome had decreased fractional anisotropy in frontal white matter regions compared with those without metabolic syndrome. These findings indicate metabolic syndrome is prevalent in this sample of younger Veterans and is related to reduced frontal white matter integrity. Early intervention for metabolic syndrome may help alleviate adverse metabolic syndrome-related brain and cognitive effects with age.

Early onset adolescent binge drinking is associated with reduced white matter integrity in post-9/11 adult veterans.

Adolescence represents a critical period of neural development during which binge drinking (BD) is prevalent. Though prior work has shown that white matter (WM) integrity is susceptible to damage from excessive alcohol intake in adults, the effect of early adolescent BD on WM health in adulthood remains unknown. Veterans with a history of BD onset before age 15 [n = 49; mean age = 31.8 years; early-onset adolescent binge drinkers (EBD)] and after age 15 [n = 290; mean age = 32.2 years; late-onset adolescent binge drinkers (LBD)] were studied with diffusion tensor imaging. Group differences in fractional anisotropy (FA; movement of water molecules along the WM) and mean diffusivity (MD; average movement of water molecules) were examined as indices of WM integrity using FreeSurfer and FMRIB Software Library (FSL) processing streams. Lower FA and higher MD are thought to represent degradations in WM integrity. A reference group (RG) of social drinkers with no history of BD (n = 31) was used to provide comparative normative data. We observed widespread decreased FA and increased MD in EBDs, compared to LBDs, as well as decreased FA in the pars triangularis, lateral orbitofrontal cortex, superior frontal cortex, isthmus cingulate, and genu and splenium of the corpus callosum EBDs also had lower WM integrity compared to the RG. Adults who initiated BD during early adolescence demonstrated decreased FA and increased MD throughout the frontostriatal circuits that mediate inhibitory control and thus may result in impulsive behavior and a predisposition for developing alcohol use disorder during adulthood.

Direct access to specific autobiographical memories is lower in healthy middle-aged to older adult Apolipoprotein E ε4 carriers compared to non-carriers.

Recent research suggests that the retrieval of autobiographical memories among cognitively healthy middle-aged and older adults is sensitive to the Apolipoprotein E ε4 (APOE4) allele, a genetic marker that increases the risk of Alzheimer's disease (AD) dementia. However, whether the APOE4-associated alteration in autobiographical memory retrieval encompasses rapid (i.e. direct retrieval) or iterative (i.e. generative retrieval) processes remains unclear. In the present study, 39 APOE4 carriers and 45 non-carriers (ages 60-80) who scored within normal limits on neuropsychological testing were cued to generate specific autobiographical events. We examined group differences in direct and generative retrieval and correlated direct and generative retrieval rates with performance on neuropsychological tests. Direct retrieval rates were lower in the APOE4 carriers compared to non-carriers. Episodic memory positively correlated with direct retrieval rates across the sample, though this relationship became non-significant when factoring in age and sex. There were no significant findings related to successful generative retrieval rates and its efficiency. In summary, compared to non-carriers, cognitively unimpaired middle-aged to older adult APOE4 carriers demonstrated greater difficulty, rapidly reconstructing specific autobiographical events without the support of semantic memory, suggesting that early autobiographical memory retrieval processes demonstrate vulnerability to AD-related risk factors.

Metabolic syndrome is associated with reduced default mode network functional connectivity in young post-9/11 Veterans.

Metabolic syndrome is a collection of health factors that increases risk for cardiovascular disease. A condition of aging, metabolic syndrome is associated with reduced brain network integrity, including functional connectivity alterations among the default mode, regions vulnerable to neurodegeneration. Prevalence of metabolic syndrome is elevated in younger populations including post-9/11 Veterans and individuals with posttraumatic stress disorder, but it is unclear whether metabolic syndrome affects brain function in earlier adulthood. Identifying early effects of metabolic syndrome on brain network integrity is critical, as these impacts could contribute to increased risk for cognitive disorders later in life for Veterans. The current study examined whether metabolic syndrome and its individual components were associated with default mode functional connectivity. We also explored the contribution of posttraumatic stress disorder and traumatic brain injury on these metabolic syndrome-brain relationships. Post-9/11 Veterans with combat deployment history (95 with and 325 without metabolic syndrome) underwent functional magnetic resonance imaging to capture seed-based resting-state functional connectivity within the default mode. The metabolic syndrome group demonstrated reduced positive functional connectivity between the posterior cingulate cortex seed and the bilateral superior frontal gyrus. Data-driven analyses demonstrated that metabolic syndrome components, particularly cholesterol and central adiposity, were associated with widespread reductions in default mode network connectivity. Functional connectivity was also reduced in participants with metabolic syndrome but without current posttraumatic stress disorder diagnosis and with traumatic brain injury history. These results suggest that metabolic syndrome disrupts resting-state functional connectivity decades earlier than prior work has shown.