Background and objectives:Olfactory function declines with aging and olfactory deficits are one of the earliest features of neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Previous studies have shown that olfaction is associated with brain volumes and cognitive function, but data are exclusively cross-sectional. We aimed to examine longitudinal associations of olfaction with changes in brain volumes and neuropsychological function.Methods:In the Baltimore Longitudinal Study of Aging, we chose the first assessment of olfaction to examine the associations with retrospective and prospective changes in neuropsychological performance and brain volumes in participants aged 50 or older using linear mixed-effects models, adjusted for demographic variables and cardiovascular disease. Olfaction was measured as odor identification scores via the 16-item Sniffin’ sticks.Results:We analyzed data from 567 (58% women, 42% men, 27% Black, 66% White, 7% Others) participants who had data on odor identification scores and brain volumetric MRI (n=420 with retrospective repeats over a mean of 3.7 years, n=280 with prospective repeats over a mean of 1.2 years). We also analyzed data from 754 participants (56% women, 44% men, 29% Black, 65% White, 6% Others) with neuropsychological assessments (n=630 with retrospective repeats over a mean of 6.6 years, n=280 with prospective repeats over a mean of 1.5 years). After adjustment, higher odor identification scores were associated with prior and subsequent slower brain atrophy in entorhinal cortex (β±SE=0.0093±0.0031,p=0.0028 and β±SE=0.0176±0.0073,p=0.0169,respectively), hippocampus (β±SE=0.0070±0.0030,p=0.0192 and β±SE=0.0173±0.0066,p=0.0089,respectively), and additional frontal and temporal areas (all p<0.05). Higher odor identification scores were also associated with prior slower decline in memory, attention, processing speed, and manual dexterity, and subsequent slower decline in attention (all p<0.05). Some associations were attenuated after exclusion of data points at and after symptom onset of cognitive impairment or dementia.Discussion:In older adults, olfaction is related to brain atrophy of specific brain regions and neuropsychological changes in specific domains over time. The observed associations are driven, in part, by those who developed cognitive impairment or dementia. Future longitudinal studies with longer follow-ups are needed to understand whether olfactory decline precedes cognitive decline and whether it is mediated through regionally-specific brain atrophy.
Background and Objectives.Although an infectious etiology of Alzheimer’s Disease (AD) has received renewed attention with a particular focus on herpes viruses, the longitudinal effects of symptomatic herpes viruses (sHHV) infection on brain structure and cognition remain poorly understood, as does the effect of sHHV on AD/neurodegeneration biomarkers.Methods.We used a longitudinal, community-based cohort to characterize the association of sHHV diagnoses with changes in 3T MRI brain volume and cognitive performance. Additionally, we related sHHV to cross-sectional differences in plasma biomarkers of AD (Aβ42/40), astrogliosis (glial fibrillary acidic protein [GFAP]) and neurodegeneration (neurofilament light [NfL]). Baltimore Longitudinal Study of Aging (BLSA) participants were recruited from the community and assessed with serial brain MRIs and cognitive exams over an average of 3.4 (SD=3.2) and 8.6 (SD=7.7) years, respectively. sHHV classification used ICD9 codes documented at comprehensive health and functional screening evaluations at each study visit. Linear mixed effects and multivariable linear regression models were used in analyses.Results.A total of 1,009 participants were included in the primary MRI analysis, 98% of whom were cognitively normal at baseline MRI (mean age = 65.7 years; 54.8% female). Having a sHHV diagnosis (N=119) was associated with longitudinal reductions in white matter volume (annual additional rate of change -0.34 cm3/year; p = 0.035), particularly in the temporal lobe. However, there was no association between sHHV and change in total brain, total gray matter, or AD signature region volume. Among the 119 participants with sHHV, exposure to antiviral treatment attenuated declines in occipital white matter (p = 0.04). Although the sHHV group had higher cognitive scores at baseline, sHHV diagnosis was associated with accelerated longitudinal declines in attention (annual additional rate of change -0.01 Z-score/year; p = 0.008). Additionally, sHHV diagnosis was associated with elevated plasma GFAP, but not related to Aβ42/40 and NfL levels.Discussion.These findings suggest an association of sHHV infection with white matter volume loss, attentional decline, and astrogliosis. Although the findings link sHHV to several neurocognitive features, the results do not support an association between sHHV and AD-specific disease processes.
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