White matter hyperintensities (WMH) in patients with cerebrovascular risk factors (CVRF), are often linked to cerebral vascular changes, but can be caused by genetic variants selectively targeting whi Show more
White matter hyperintensities (WMH) in patients with cerebrovascular risk factors (CVRF), are often linked to cerebral vascular changes, but can be caused by genetic variants selectively targeting white matter. In addition, WMH can be present in neurodegenerative disorders such as frontotemporal lobar degeneration (FTLD) and are linked to some FTLD genetic variants. This study aims to investigate WMH burden in patients with behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA) versus controls and to evaluates the influence of CVRF. This cross-sectional retrospective analysis examined individuals meeting research diagnostic criteria for bvFTD and svPPA with high-quality structural MRI at the UCSF Memory and Aging Center between September 2008 and December 2021. WMH burden and spatial distribution were assessed by disease group compared to age- and sex-matched controls and associations with CVRF evaluated. We included 109 individuals with bvFTD [mean age (SD) 62.9 (8.6), 40% female], 47 with svPPA [mean (SD) age 65.4 (7.5), 51% female], and matched controls. After adjusting for age, bvFTD and svPPA are associated with elevated WMH burden independent of CVRF. In bvFTD, WMH are primarily distributed within the frontal lobes, while svPPA shows widespread distribution across lobes. Study limitations include its retrospective, single-center design and limited power for genetic subgroup analyses. Show less
Antiretroviral therapies have become widely available, and as a result, individuals infected with the human immunodeficiency virus (HIV) are living longer, and becoming integrated into the geriatric p Show more
Antiretroviral therapies have become widely available, and as a result, individuals infected with the human immunodeficiency virus (HIV) are living longer, and becoming integrated into the geriatric population. Around half of the HIV+ population shows some degree of cognitive impairment, but it is unknown how their neural networks and brain connectivity compare to those of noninfected people. Here we combined magnetic resonance imaging-based cortical parcellations with high angular resolution diffusion tensor imaging tractography in 55 HIV-seropositive patients and 30 age-matched controls, to map white matter connections between cortical regions. We set out to determine selective virus-associated disruptions in the brain's structural network. All individuals in this study were aged 60-80, with full access to antiretroviral therapy. Frontal and motor connections were compromised in HIV+ individuals. HIV+ people who carried the apolipoprotein E4 allele (ApoE4) genotype-which puts them at even greater risk for neurodegeneration-showed additional network structure deficits in temporal and parietal connections. The ApoE4 genotype interacted with duration of illness. Carriers showed greater brain network inefficiencies the longer they were infected. Neural network deficiencies in HIV+ populations exceed those typical of normal aging, and are worse in those genetically predisposed to brain degeneration. This work isolates neuropathological alterations in HIV+ elders, even when treated with antiretroviral therapy. Network impairments may contribute to the neuropsychological abnormalities in elderly HIV patients, who will soon account for around half of all HIV+ adults. Show less