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Introduction: We examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up.Methods: Framingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified.Results: Baseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion from normal cognition to MCI at 6.5-year follow-up. Annualized change rates in total cerebral brain volume and hippocampal volume were associated with conversion from normal cognition to MCI to follow-up.Discussion: Baseline WMH and hippocampal volume are markers that are both associated with conversion from normal cognition to MCI, highlighting the role of both vascular lesions and neurodegeneration in MCI. [ABSTRACT FROM AUTHOR]

We investigated whether midlife pulse pressure is associated with brain atrophy and cognitive decline, and whether the association was modified by apolipoprotein-E ε4 (APOE-ε4) and hypertension. Participants (549 stroke-free and dementia-free Framingham Offspring Cohort Study participants, age range=55.0 to 64.9 y) underwent baseline neuropsychological and magnetic resonance imaging (subset, n=454) evaluations with 5- to 7-year follow-up. Regression analyses investigated associations between baseline pulse pressure (systolic-diastolic pressure) and cognition, total cerebral volume and temporal horn ventricular volume (as an index of smaller hippocampal volume) at follow-up, and longitudinal change in these measures. Interactions with APOE-ε4 and hypertension were assessed. Covariates included age, sex, education, assessment interval, and interim stroke. In the total sample, baseline pulse pressure was associated with worse executive ability, lower total cerebral volume, and greater temporal horn ventricular volume 5 to 7 years later, and longitudinal decline in executive ability and increase in temporal horn ventricular volume. Among APOE-ε4 carriers only, baseline pulse pressure was associated with longitudinal decline in visuospatial organization. Findings indicate arterial stiffening, indexed by pulse pressure, may play a role in early cognitive decline and brain atrophy in mid to late life, particularly among APOE-ε4 carriers. [ABSTRACT FROM AUTHOR]

Objective: To examine how phenotype affects longitudinal decline on the Mini-Mental State Examination (MMSE) in patients with frontotemporal lobar degeneration (FTLD) and Alzheimer disease (AD). Background: The MMSE is the most commonly administered assessment for dementia severity; however, the effects of phenotype on longitudinal MMSE performance in FTLD and AD have not been extensively studied. Methods: Data from 185 patients diagnosed with AD (n = 106) and 3 FTLD (n = 79) phenotypes [behavioral variant frontotemporal dementia (bvFTD), nonfiuent agrammatic variant of primary progressive aphasia (nfaPPA), and semantic variant PPA (svPPA)] were collected for up to 52 months since initial evaluation. Results: Differential rates of decline were noted in that MMSE scores declined more precipitously for AD and svPPA compared with bvFTD and nfaPPA patients (P = 0.001). The absolute 4-year MMSE decline given median baseline MMSE for bvFTD [14.67; 95% confidence interval (CI), 14.63-14.71] and nfaPPA (11.02; 95% CI, 10.98-11.06) were lower than svPPA (22.32; 95% CI, 22.29-22.34) or AD (22.24; 95% CI, 22.22-22.26). Conclusions: These data suggest that within-group AD and FTLD phenotypes present distinct patterns of longitudinal decline on the MMSE. MMSE may not be adequately sensitive to track disease progression in some phenotypes of FTLD. [ABSTRACT FROM AUTHOR]

Objective: To examine how phenotype affects longitudinal decline on the Mini-Mental State Examination (MMSE) in patients with frontotemporal lobar degeneration (FTLD) and Alzheimer disease (AD)., Background: The MMSE is the most commonly administered assessment for dementia severity; however, the effects of phenotype on longitudinal MMSE performance in FTLD and AD have not been extensively studied., Methods: Data from 185 patients diagnosed with AD (n=106) and 3 FTLD (n=79) phenotypes [behavioral variant frontotemporal dementia (bvFTD), nonfluent agrammatic variant of primary progressive aphasia (nfaPPA), and semantic variant PPA (svPPA)] were collected for up to 52 months since initial evaluation., Results: Differential rates of decline were noted in that MMSE scores declined more precipitously for AD and svPPA compared with bvFTD and nfaPPA patients (P=0.001). The absolute 4-year MMSE decline given median baseline MMSE for bvFTD [14.67; 95% confidence interval (CI), 14.63-14.71] and nfaPPA (11.02; 95% CI, 10.98-11.06) were lower than svPPA (22.32; 95% CI, 22.29-22.34) or AD (22.24; 95% CI, 22.22-22.26)., Conclusions: These data suggest that within-group AD and FTLD phenotypes present distinct patterns of longitudinal decline on the MMSE. MMSE may not be adequately sensitive to track disease progression in some phenotypes of FTLD.