Worse Fluency Research Articles

Associations between Later‐life Cerebrovascular Reactivity and Brain Structure and Cognitive Decline: A Longitudinal Study in an Aging Cohort with Varying Dementia Risks

AbstractBackgroundCerebrovascular reactivity (CVR) is implicated in the progression of dementia, though the underlying mechanisms is not understood. This study examines the relationships between CVR and brain structure and cognitive decline, moderated by mid‐life dementia risk.Method163 participants from the Whitehall‐II cohort underwent neuropsychological testing and MRI, including T1‐weighted, FLAIR, and DTI sequences, at two phases (Phase‐I: mean age=68.2±4.4; Phase‐II: mean age=76.9±4.5). CVR was quantified via BOLD response to 5% CO2 only at Phase‐II. Linear regression tested the Phase‐II and Phase‐I to Phase‐II associations between CVR and brain and cognitive outcomes (Table 1), alongside its interaction with dementia risks. Post‐hoc analysis clarified the extent of these associations among different risk groups.ResultTables 2 and 3 list significant cross‐sectional and longitudinal results, respectively. At Phase‐II, global CVR was positively associated with volume of left nucleus accumbens, and temporoparietal junction (p<0.03). Parietal CVR was positively associated with left hippocampus volume (p=0.03). These associations were more pronounced in the low‐risk group. Temporal CVR was related to thalamus volume (p<0.05) across all participants, with associations of the right thalamus exclusive to the high‐risk group (p=0.03). Longitudinally, lower global and regional CVR at Phase‐II was linked to greater reduction in temporoparietal junction volume (p<0.04). In high‐risk individuals, lower frontal, parietal, or global CVR was linked to larger volume declines in total grey matter or right thalamus respectively (p<0.05). Across all participants, lower parietal CVR at follow‐up was linked to greater FA reductions and RD increases between examinations in the corpus callosum (p=0.02) and to greater declines in FA and increases in MD, RD, and L1 in the cingulum bundle (p<0.04), with these effects being more pronounced in the low‐risk group. At Phase‐II, lower parietal and temporal CVR was associated with worse fluency and intelligence, respectively, in high‐risk individuals (p<0.05). Lower frontal CVR was linked to more executive function decline in the low‐risk group over‐time (p=0.03).ConclusionThis study highlights the differential impacts of global and regional CVR on brain structure and cognitive changes dependent on mid‐life dementia risks, which provides evidence for CVR as a potential biomarker for dementia and age‐related cognitive change.

COGNITIVE EFFECTS OF PM2.5 EXPOSURE FROM MID-LIFE TO EARLY OLD AGE

Abstract Air pollution exposure is a notable public health hazard with adverse effects on multiple health outcomes as well as with increased risk of developing cognitive impairment, Alzheimer’s disease, and related dementias. Few studies examine associations between air pollution exposure in midlife or the transition from midlife to old age. We examined associations between exposure in midlife and cognitive functioning in early old age in ~800 men from the Vietnam Era Twin Study of Aging. Measures included PM2.5 and NO2 exposure in the three years prior to the time 1 (mean age 56; range 51-61) assessment, and cognitive performance in 5 domains at time 1 and time 2 (mean age 68; range 65-72). Analyses adjusted for multiple health and lifestyle covariates. Cognitive performance in all domains was worse at age 68 than at age 56. There was a main effect of midlife PM2.5 on verbal fluency; greater PM2.5 exposure was associated with worse fluency. This association was at a trend level for NO2. In addition, we found significant PM2.5-by-APOE genotype interactions. Increased exposure to PM2.5 in midlife was related to lower executive function and working memory performance in APOE-ε4 carriers, but not non-carriers. Both early executive deficits and APOE-ε4 status have been associated with increased risk for progression to mild cognitive impairment and Alzheimer’s disease. The present results indicate that midlife PM2.5 exposure in men is an additional factor contributing to poorer frontal-executive function, and that APOEε4 carriers are more susceptible to the deleterious effects of PM2.5.

Construct and Criterion-Related Validity of the Clinical Frailty Scale in Persons With HIV.

The co-occurrence of frailty and cognitive impairment in older (50+ years) persons with HIV (PWH) is common and increases the risk of poor outcomes. In HIV clinics, the most commonly used frailty measures are the frailty phenotype (FP), which requires measuring grip strength and gait speed to implement, and the frailty index (FI) based on comprehensive health data collected on patients. We examined construct and criterion-related validity (as it predicts cognition) of the Clinical Frailty Scale (CFS), a less resource-intensive approach for assessing frailty, in relation to these more commonly used frailty assessments (FP and FI). A total of 143 older (age 50+) PWH (mean age 57 years; 88% male) seen at the Southern Alberta Clinic underwent both frailty screening with the FP, CFS, and FI and neuropsychological testing. Mixed-effects regressions examined the associations between frailty status and cognition. Concordance with the FP was slightly superior for the CFS than the FI. The FP and CFS had similar associations with domain-specific cognitive performance with frail PWH performing worse than nonfrail individuals on tests requiring manual dexterity (Trail Making Part A and B; Symbol Digit; and Grooved Pegboard; P values <0.05). Neither were associated with executive function, learning, or memory performance. The FI was associated with worse fluency, fine motor skills (Grooved Pegboard), and Trail Making Part A. The CFS is a simple screening tool with good construct and criterion-related validity. It was associated with a similar pattern of cognitive deficits as the FP. If confirmed and the associations are extended to other clinically significant characteristics and outcomes, the CFS can be considered as an alternative to the FP and FI in assessing frailty in older PWH.

Effects of APOE ε4, age, and HIV on glial metabolites and cognitive deficits.

We aimed to evaluate the combined effects of HIV and APOE ε4 allele(s) on glial metabolite levels, and on known cognitive deficits associated with either condition, across the ages. One hundred seventy-seven participants, primarily of white and mixed race (97 seronegative subjects: aged 44.7 ± 1.3 years, 85 [87.6%] men, 28 [28.9%] APOE ε4+; 80 HIV+ subjects: aged 47.3 ± 1.1 years, 73 [91.3%] men, 23 [28.8%] APOE ε4+), were assessed cross-sectionally for metabolite concentrations using proton magnetic resonance spectroscopy in 4 brain regions and for neuropsychological performance. Frontal white matter myo-inositol was elevated in subjects with HIV across the age span but showed age-dependent increase in seronegative subjects, especially in APOE ε4+ carriers. In contrast, only seronegative APOE ε4+ subjects showed elevated myo-inositol in parietal cortex. All APOE ε4+ subjects had lower total creatine in basal ganglia. While all HIV subjects showed greater cognitive deficits, HIV+ APOE ε4+ subjects had the poorest executive function, fluency memory, and attention/working memory. Higher myo-inositol levels were associated with poorer fine motor function across all subjects, slower speed of information processing in APOE ε4+ subjects, and worse fluency in HIV+ APOE ε4+ subjects. In frontal white matter of subjects with HIV, the persistent elevation and lack of normal age-dependent increase in myo-inositol suggest that persistent glial activation attenuated the typical antagonistic pleiotropic effects of APOE ε4 on neuroinflammation. APOE ε4 negatively affects energy metabolism in brain regions rich in dopaminergic synapses. The combined effects of HIV infection and APOE ε4 may lead to greater cognitive deficits, especially in those with greater neuroinflammation. APOE ε4 allele(s) may be a useful genetic marker to identify white and mixed-race HIV subjects at risk for cognitive decline.