ABSTRACT
INTRODUCTION: Prospective memory (PM) deficits have been documented in multiple sclerosis (MS). This study aimed to explore the specific types of errors made by persons with MS (PwMS), including differences between PwMS and healthy controls (HC) and PwMS who do and do not have impairments in processing speed and/or verbal learning and memory. METHOD: PwMS (n = 111) and HC (n = 75) completed the Memory for Intentions Test (MIST), an objective measure of PM that has five types of errors that can be coded (PM failure, task substitution, loss of content, loss of time, and random errors). The number and types of PM errors were calculated for the overall MIST and six subscales, which break down performance by types of delay (2-Minute and 15-Minute), cue (Time and Event), and response (Verbal and Action). Impairment was defined as performing < 1.5 SD on either the Symbol Digit Modalities Test (SDMT) or Rey Auditory Verbal Learning Test (RAVLT). Bivariate analyses were used to examine group differences, with post-hoc pairwise comparisons with Bonferroni corrections. RESULTS: Nearly 93% of PwMS made at least one PM error, compared to 76% of HC (V = .24, p = .001). The most commonly made PM error by PwMS was loss of content errors (45.0%). PwMS made significantly more task substitution errors (26.4% vs. 7.6%, p < .001) and fewer loss of time errors (9.5% vs. 21.2%, p < .001) than HC. Impaired PwMS made more errors than non-impaired PwMS, specifically PM failures on time-based tasks. CONCLUSIONS: PM errors are common in PwMS, particularly when there are longer delays and time-based cues. Not only do PwMS make more errors than demographically similar HC, but they exhibit different cognitive process failures.
ABSTRACT
Obesity and excess adiposity at midlife are risk factors for Alzheimer disease (AD). Visceral fat is known to be associated with insulin resistance and a pro-inflammatory state, the two mechanisms involved in AD pathology. We assessed the association of obesity, MRI-determined abdominal adipose tissue volumes, and insulin resistance with PET-determined amyloid and tau uptake in default mode network areas, and MRI-determined brain volume and cortical thickness in AD cortical signature in the cognitively normal midlife population. Thirty-two middle-aged (age: 51.27±6.12 years, 15 males, body mass index (BMI): 32.28±6.39 kg/m2) cognitively normal participants, underwent bloodwork, brain and abdominal MRI, and amyloid and tau PET scan. Visceral and subcutaneous adipose tissue (VAT, SAT) were semi-automatically segmented using VOXel Analysis Suite (Voxa). FreeSurfer was used to automatically segment brain regions using a probabilistic atlas. PET scans were acquired using [11C]PiB and AV-1451 tracers and were analyzed using PET unified pipeline. The association of brain volumes, cortical thicknesses, and PiB and AV-1451 standardized uptake value ratios (SUVRs) with BMI, VAT/SAT ratio, and insulin resistance were assessed using Spearman's partial correlation. VAT/SAT ratio was associated significantly with PiB SUVRs in the right precuneus cortex (p=0.034) overall, controlling for sex. This association was significant only in males (p=0.044), not females (p=0.166). Higher VAT/SAT ratio and PiB SUVRs in the right precuneus cortex were associated with lower cortical thickness in AD-signature areas predominantly including bilateral temporal cortices, parahippocampal, medial orbitofrontal, and cingulate cortices, with age and sex as covariates. Also, higher BMI and insulin resistance were associated with lower cortical thickness in bilateral temporal poles. In midlife cognitively normal adults, we demonstrated higher amyloid pathology in the right precuneus cortex in individuals with a higher VAT/SAT ratio, a marker of visceral obesity, along with a lower cortical thickness in AD-signature areas associated with higher visceral obesity, insulin resistance, and amyloid pathology.
