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Multi-compartment modelling of white matter microstructure using Neurite Orientation Dispersion and Density Imaging (NODDI) can provide information on white matter health through neurite density index and free water measures. We hypothesized that cerebrovascular disease, Alzheimer's disease, and TDP-43 proteinopathy would be associated with distinct NODDI readouts of white matter damage which would be informative for identifying the substrate for cognitive impairment. We identified two independent cohorts with multi-shell diffusion MRI, amyloid and tau PET, and cognitive assessments: specifically, a population-based cohort of 347 elderly randomly sampled from the Olmsted county, Minnesota, population and a clinical research-based cohort of 61 amyloid positive Alzheimer's dementia participants. We observed an increase in free water and decrease in neurite density using NODDI measures in the genu of the corpus callosum associated with vascular risk factors, which we refer to as the vascular white matter component. Tau PET signal reflective of 3R/4R tau deposition was associated with worsening neurite density index in the temporal white matter where we measured parahippocampal cingulum and inferior temporal white matter bundles. Worsening temporal white matter neurite density was associated with (antemortem confirmed) FDG TDP-43 signature. Post-mortem neuropathologic data on a small subset of this sample lend support to our findings. In the community-dwelling cohort where vascular disease was more prevalent, the NODDI vascular white matter component explained variability in global cognition (partial R2 of free water and neurite density = 8.3%) and MMSE performance (8.2%) which was comparable to amyloid PET (7.4% for global cognition and 6.6% for memory). In the AD dementia cohort, tau deposition was the greatest contributor to cognitive performance (9.6%), but there was also a non-trivial contribution of the temporal white matter component (8.5%) to cognitive performance. The differences observed between the two cohorts were reflective of their distinct clinical composition. White matter microstructural damage assessed using advanced diffusion models may add significant value for distinguishing the underlying substrate (whether cerebrovascular disease versus neurodegenerative disease caused by tau deposition or TDP-43 pathology) for cognitive impairment in older adults. [ABSTRACT FROM AUTHOR]

Background. Minnesota (MN) is home to one of the highest number of refugees in the United States. The primary objective of this study was to evaluate the prevalence of latent and active tuberculosis (TB) infection in primary refugee arrivals to MN. Secondary objectives were to determine the association of TB infection with gender, age, and ethnicity of the refugees. Methods. A retrospective study of primary refugee arrivals to MN between January 1, 1997, and December 31, 2001, was conducted. Chi-square tests and logistic regression analyses were used to assess the association of TB infection with gender, age, and ethnicity. Results. Of the 9,842 refugees who had Mantoux test results, 4,990 (50.7%) had a positive test. A positive test was more common in men [odds ratio (OR) = 1.6; p < 0.0001], in Africans (OR = 1.6, p = <0.0001), and increased with 10-year age intervals (OR = 1.4; p < 0.0001). A total of 116 (0.8%) refugees received treatment for active TB. Active TB was more common in men (OR = 1.7; p = 0.006), African ethnicity (OR = 4.3; p < 0.0001), and increased with 10-year age intervals (OR = 1.1; p = 0.05). Conclusions. Screening and treatment for latent and active TB should be actively managed among refugees resettling in the United States, as this is common and can have significant public health implications. [ABSTRACT FROM AUTHOR]

Importance: Intellectual lifestyle enrichment throughout life is increasingly viewed as a protective strategy against commonly observed cognitive decline in the older population., Objectives: To investigate the association of lifetime intellectual enrichment with baseline cognitive performance and rate of cognitive decline in an older population without dementia and to estimate the years of protection provided against cognitive impairment by these factors., Design, Setting, and Participants: Prospective analysis of individuals enrolled from October 1, 2004, and in 2008 and 2009 in the Mayo Clinic Study of Aging, a longitudinal, population-based study of cognitive aging in Olmsted County, Minnesota. We studied 1995 individuals without dementia (1718 cognitively normal individuals and 277 individuals with mild cognitive impairment) who completed intellectual lifestyle enrichment measures at baseline and underwent at least 1 follow-up visit., Main Outcomes and Measures: We studied the effect of lifetime intellectual enrichment by separating the variables into 2 nonoverlapping principal components: education/occupation score and mid/late-life cognitive activity based on self-report questionnaires. A global cognitive z score served as the summary cognition measure. Linear mixed-effects models were used to investigate the associations of demographic and intellectual enrichment measures with global cognitive z score trajectories., Results: Baseline cognitive performance was lower in older individuals; individuals with lower education/occupation score, lower mid/late-life cognitive activity, and APOE genotype; and men (P < .001). The interaction between the 2 intellectual enrichment measures was significant (P < .03) such that the beneficial effect of mid/late-life cognitive activity on baseline cognitive performance was reduced with increasing education/occupation score. Only baseline age, mid/late-life cognitive activity, and APOE4 genotype were significantly associated with longitudinal change in cognitive performance from baseline (P < .05). For APOE4 carriers with high lifetime intellectual enrichment (75th percentile of education/occupation score and midlife to late-life cognitive activity), the onset of cognitive impairment was approximately 8.7 years later compared with low lifetime intellectual enrichment (25th percentile of education/occupation score and mid/late-life cognitive activity)., Conclusions and Relevance: Higher education/occupation scores were associated with higher levels of cognition. Higher levels of mid/late-life cognitive activity were also associated with higher levels of cognition, but the slope of this association slightly increased over time. Lifetime intellectual enrichment might delay the onset of cognitive impairment and be used as a successful preventive intervention to reduce the impending dementia epidemic.