This study investigated the relationship between insulin-resistance and constituent components of executive function in a sample of neurologically intact older adult subjects using the homeostasis model assessment (HOMA-IR) and latent factors of working memory, cognitive control and processing speed derived from confirmatory factor analysis. Low-density lipoprotein (LDL), mean arterial pressure (MAP), along with body mass index (BMI) and white matter hypointensity (WMH) were used to control for vascular risk factors, adiposity and cerebrovascular injury. The study included 119 elderly subjects recruited from the University of California, San Francisco Memory and Aging Center. Subjects underwent neuropsychological assessment, fasting blood draw and brain magnetic resonance imaging (MRI). Partial correlations and linear regression models were used to examine the HOMA-IR-executive function relationship. Pearson correlation adjusting for age showed a significant relationship between HOMA-IR and working memory (rp = -.18; p = .047), a trend with cognitive control (rp = -.17; p = .068), and no relationship with processing speed (rp = .013; p = .892). Linear regression models adjusting for demographic factors (age, education, and gender), LDL, MAP, BMI, and WMH indicated that HOMA-IR was negatively associated with cognitive control (r = -.256; p = .026) and working memory (r = -.234; p = .054). These results suggest a greater level of peripheral insulin-resistance is associated with decreased cognitive control and working memory. After controlling for demographic factors, vascular risk, adiposity and cerebrovascular injury, HOMA-IR remained significantly associated with cognitive control, with working memory showing a trend. These findings substantiate the insulin-resistance-executive function hypothesis and suggest a complex interaction, demonstrated by the differential impact of insulin-resistance on processing speed and specific aspects of executive function.

Objective

Vascular risk factors like hyperlipidemia may adversely affect brain function. We hypothesized that increased serum triglycerides are associated with decreased executive function and memory in nondemented elderly subjects. We also researched possible vascular mediators and white matter microstructure as assessed with diffusion tensor imaging (DTI).

Design/method

Participants were 251 nondemented elderly adults (54% male) with a mean age of 78 (SD = 6.4; range: 62-94) years and a mean education of 15.6 (SD = 2.9; range: 8-23) years. Fasting blood samples were used to detect serum triglyceride and low-density lipoprotein (LDL) levels along with ApoE4 status. DTI was used to determine whole brain fractional anisotropy (FA). Composite executive and memory scores were derived from item response theory. Clinical Dementia Rating (CDR) scores provided informant-based measures of daily functioning.

Results

Triglyceride levels were inversely correlated with executive function, but there was no relationship with memory. Controlling for age, gender, and education did not affect this correlation. This relationship persisted after controlling for vascular risk factors like LDL, total cholesterol, CDR and ApoE4 status. Lastly, adding whole-brain FA to the model did not affect the correlation between triglycerides and executive function.

Conclusion

Triglyceride levels are inversely correlated with executive function in nondemented elderly adults after controlling for age, education, gender, total cholesterol, LDL, ApoE4 status, CDR, and white-matter microstructure. The fact that the effect of triglycerides on cognition was not clearly mediated by vascular risks or cerebrovascular injury raises questions about widely held assumptions of how triglycerides might impact cognition function. (PsycINFO Database Record

Objective: To examine the impact of genetic, inflammatory, cardiovascular, lifestyle, and neuroanatomical factors on cognitive processing speed (CPS) change over time in functionally intact older adults. Methods: This observational study conducted over two time points, included 120 community dwelling cognitively normal older adults between the ages of 60 and 80 from the University of California San Francisco Memory and Aging Center. Participants were followed with composite measures of CPS, calculated based on norms for 20-30 year-olds. Variables of interest were AD risk genes (APOE, CR1), markers of inflammation (interleukin 6) and cardiovascular health (BMI, LDL, HDL, mean arterial pressure, fasting insulin), self-reported physical activity, and corpus callosum (CC) volumes. The sample was divided into three groups: 17 "resilient-agers" with fast and stable processing speed; 56 "average-agers" with average and stable processing speed; and 47 "sub-agers" with average baseline speed who were slower at follow-up. Results: Resilient-agers had larger baseline CC volumes than sub-agers (p < 0.05). Resilient-agers displayed lower levels of interleukin-6 (IL-6) and insulin (ps < 0.05) than sub-agers, and reported more physical activity than both average- and sub-agers (ps < 0.01). In a multinomial logistic regression, physical activity and IL-6 predicted average- and sub-ager groups. Resilient-agers displayed a higher frequency of APOE e4 and CR1 AA/AG alleles. Conclusion: Robust and stable CPS is associated with larger baseline CC volumes, lower levels of inflammation and insulin, and greater self-reported physical activity. These findings highlight the relevance of neuroanatomical, biological, and lifestyle factors in the identification and prediction of heterogeneous cognitive aging change over time.

Background and purpose

Carotid atherosclerosis is a risk factor for cerebrovascular disease in older adults. Although age-related cognitive decline has been associated with cerebrovascular disease, not much is known about the consequences of carotid atherosclerosis on longitudinal cognitive function. This study examines the longitudinal relationship between atherosclerosis and cognition in a sample of non-demented older subjects using baseline measurements of carotid intima media thickness (CIMT) and annual cognitive measures of executive function (EXEC) and verbal memory (MEM).

Methods

Baseline measurements included CIMT derived from B-mode carotid artery ultrasound, structural T1-weighted images of white matter hypointensities (WMH), white matter lesions (WML), and cerebral infarct. Hypertension, low-density lipoprotein (LDL), diabetes, and waist to hip ratios (WHR) were included as covariates in our models to control for cerebrovascular risks and central adiposity. Annual composite scores of EXEC and MEM functions were derived from item response theory. Linear mixed models were used to model longitudinal cognitive change.

Results

A significant inverse relationship was found between baseline CIMT and annual EXEC score, but not annual MEM score. Subjects included in the highest 4th quartile of CIMT showed a rate of annual decline in EXEC score that was significant relative to subjects in lower quartile groups (p<0.01). The relationship between the 4th quartile of CIMT and annual EXEC score remained significant after independently adjusting for imaging measures of white matter injury and cerebral infarct.

Conclusions

Older adult subjects with the highest index of CIMT showed an annual decline in EXEC scores that was significant relative to subjects with lower quartile measurements of CIMT, independent of our measures of white matter injury and cerebral infarct. Our findings suggest that elevated measures of CIMT may mark an atherosclerotic state, resulting in a decline in executive function and not memory in non-demented older adults.

Primary progressive aphasia is a neurodegenerative clinical syndrome that presents in adulthood with an isolated, progressive language disorder. Three main clinical/anatomical variants have been described, each associated with distinctive pathology. A high frequency of neurodevelopmental learning disability in primary progressive aphasia has been reported. Because the disorder is heterogeneous with different patterns of cognitive, anatomical and biological involvement, we sought to identify whether learning disability had a predilection for one or more of the primary progressive aphasia subtypes. We screened the University of California San Francisco Memory and Aging Center's primary progressive aphasia cohort (n = 198) for history of language-related learning disability as well as hand preference, which has associations with learning disability. The study included logopenic (n = 48), non-fluent (n = 54) and semantic (n = 96) variant primary progressive aphasias. We investigated whether the presence of learning disability or non-right-handedness was associated with differential effects on demographic, neuropsychological and neuroimaging features of primary progressive aphasia. We showed that a high frequency of learning disability was present only in the logopenic group (χ(2) = 15.17, P < 0.001) and (χ(2) = 11.51, P < 0.001) compared with semantic and non-fluent populations. In this group, learning disability was associated with earlier onset of disease, more isolated language symptoms, and more focal pattern of left posterior temporoparietal atrophy. Non-right-handedness was instead over-represented in the semantic group, at nearly twice the prevalence of the general population (χ(2) = 6.34, P = 0.01). Within semantic variant primary progressive aphasia the right-handed and non-right-handed cohorts appeared homogeneous on imaging, cognitive profile, and structural analysis of brain symmetry. Lastly, the non-fluent group showed no increase in learning disability or non-right-handedness. Logopenic variant primary progressive aphasia and developmental dyslexia both manifest with phonological disturbances and posterior temporal involvement. Learning disability might confer vulnerability of this network to early-onset, focal Alzheimer's pathology. Left-handedness has been described as a proxy for atypical brain hemispheric lateralization. As non-right-handedness was increased only in the semantic group, anomalous lateralization mechanisms might instead be related to frontotemporal lobar degeneration with abnormal TARDBP. Taken together, this study suggests that neurodevelopmental signatures impart differential trajectories towards neurodegenerative disease.