This study examined biological sex differences in the development of mild cognitive impairment (MCI) and probable Alzheimer's disease (AD) development as predicted by changes in the hippocampus or white matter hyperintensities. A secondary data analysis of the National Alzheimer's Coordinating Center Uniform Data Set was conducted. We selected samples of participants with normal cognition at baseline who progressed to MCI (n = 483) and those who progressed to probable AD (n = 211) to determine if hippocampal volume or white matter hyperintensities (WMH) at baseline predicted progression to probable AD or MCI and whether the rate of progression differed between men and women. The survival analyses indicated that changes in hippocampal volumes affected the progression to probable AD (HR = 0.535, 95% CI [0.300-0.953]) only among women. White men had an increased rate of progression to AD (HR = 4.396, CI [1.012-19.08]; HR = 4.665, 95% CI [1.072-20.29]) compared to men in other race and ethnic groups. Among women, increases in hippocampal volume ratio led to decreased rates of progressing to MCI (HR = 0.386, 95% CI [0.166-0.901]). Increased WMH among men led to faster progression to MCI (HR = 1.048. 95% CI [1.011-1.086]). Women and men who were older at baseline were more likely to progress to MCI. In addition, results from longitudinal analyses showed that women with a higher CDR global score, older age at baseline, or more disinhibition symptoms experienced higher odds of MCI development. Changes in hippocampal volumes affect the progression to or odds of probable AD (and MCI) more so among women than men, while changes in WMH affected the progression to MCI only among men.

Objectives: The aim of this study was to determine the presence and severity of potential cultural and language bias in widely used cognitive and other assessment instruments, using structural MRI measures of neurodegeneration as biomarkers of disease stage and severity. Methods: Hispanic (n = 75) and White non-Hispanic (WNH) (n = 90) subjects were classified as cognitively normal (CN), amnestic mild cognitive impairment (aMCI) and mild dementia. Performance on the culture-fair and educationally fair Fuld Object Memory Evaluation (FOME) and Clinical Dementia Rating Scale (CDR) between Hispanics and WNHs was equivalent, in each diagnostic group. Volumetric and visually rated measures of the hippocampus entorhinal cortex, and inferior lateral ventricles (ILV) were measured on structural MRI scans for all subjects. A series of analyses of covariance, controlling for age, depression, and education, were conducted to compare the level of neurodegeneration on these MRI measures between Hispanics and WNHs in each diagnostic group. Results: Among both Hispanics and WNH groups there was a progressive decrease in volume of the hippocampus and entorhinal cortex, and an increase in volume of the ILV (indicating increasing atrophy in the regions surrounding the ILV) from CN to aMCI to mild dementia. For equivalent levels of performance on the FOME and CDR, WNHs had greater levels of neurodegeneration than did Hispanic subjects. Conclusions: Atrophy in medial temporal regions was found to be greater among WNH than Hispanic diagnostic groups, despite the lack of statistical differences in cognitive performance between these two ethnic groups. Presumably, unmeasured factors result in better cognitive performance among WNH than Hispanics for a given level of neurodegeneration.

Background: Plasma NfL (pNfL) levels are elevated in many neurological disorders. However, the utility of pNfL in a clinical setting has not been established. Objective: In a cohort of diverse older participants, we examined: 1) the association of pNfL to age, sex, Hispanic ethnicity, diagnosis, and structural and amyloid imaging biomarkers; and 2) its association to baseline and longitudinal cognitive and functional performance. Methods: 309 subjects were classified at baseline as cognitively normal (CN) or with cognitive impairment. Most subjects had structural MRI and amyloid PET scans. The most frequent etiological diagnosis was Alzheimer’s disease (AD), but other neurological and neuropsychiatric disorders were also represented. We assessed the relationship of pNfL to cognitive and functional status, primary etiology, imaging biomarkers, and to cognitive and functional decline. Results: pNfL increased with age, degree of hippocampal atrophy, and amyloid load, and was higher in females among CN subjects, but was not associated with Hispanic ethnicity. Compared to CN subjects, pNfL was elevated among those with AD or FTLD, but not those with neuropsychiatric or other disorders. Hippocampal atrophy, amyloid positivity and higher pNfL levels each added unique variance in predicting greater functional impairment on the CDR-SB at baseline. Higher baseline pNfL levels also predicted greater cognitive and functional decline after accounting for hippocampal atrophy and memory scores at baseline. Conclusion: pNfL may have a complementary and supportive role to brain imaging and cognitive testing in a memory disorder evaluation, although its diagnostic sensitivity and specificity as a stand-alone measure is modest. In the absence of expensive neuroimaging tests, pNfL could be a used for differentiating neurodegenerative disease from neuropsychiatric disorders.

Mild AD could be distinguished from mild LBD by the severity of MTA and memory impairment. The severity of parkinsonism was associated with the severity of atrophy in the third ventricular region, but was not a good discriminator between AD and LBD.