Functional magnetic resonance imaging (MRI) studies have demonstrated a critical role of hippocampus and inferior frontal gyrus (IFG) in associative memory. Similarly, evidence from structural MRI ...studies suggests a relationship between gray-matter volume in these regions and associative memory. However, how brain volume and activity relate to each other during associative-memory formation remains unclear. Here, we used joint independent component analysis (jICA) to examine how gray-matter volume and brain activity would be associated during associative encoding, especially in medial-temporal lobe (MTL) and IFG. T1-weighted images were collected from 27 young adults, and functional MRI was employed during intentional encoding of object pairs. A subsequent recognition task tested participants’ memory performance. Unimodal analyses using voxel-based morphometry revealed that participants with better associative memory showed larger gray-matter volume in left anterior hippocampus. Results from the jICA revealed one component that comprised a covariance pattern between gray-matter volume in anterior and posterior MTL and encoding-related activity in IFG. Our findings suggest that gray matter within the MTL modulates distally distinct parts of the associative encoding circuit, and extend previous studies that demonstrated MTL-IFG functional connectivity during associative memory tasks.
•Younger adults with better associative memory show larger gray-matter volume in left anterior hippocampus.•Gray-matter volume in medial temporal lobes covaries with encoding-related activity in inferior frontal gyrus.•The association between gray-matter volume and encoding-related activity did not predict associative memory performance.
The purpose of this study was to examine the associations between combined and individual cerebral small vessel disease (cSVD) markers on future walking speed over 9 years; and to explore whether ...these associations varied by the presence of cardiovascular risk factors (CRFs).
This population-based cohort study included 331 adults, aged ≥60 years, without limitation in walking speed (≥0.8 m/s). At baseline, cSVD markers, including white matter hyperintensities (WMH), lacunes, and perivascular spaces (PVS), were assessed on magnetic resonance imaging. The modifiable CRFs (physical inactivity, heavy alcohol consumption, smoking, hypertension, high total cholesterol, diabetes, and overweight/obese) were combined into a score. The association between baseline cSVD markers and the decline in walking speed was examined using linear mixed-effects models, whereas Cox proportional hazards models were used to estimate the association with walking speed limitation (defined as < 0.8 m/s) over the follow-up.
Over the follow-up period, 76 (23.0%) persons developed walking speed limitation. Participants in the highest tertile of the combined cSVD marker score had a hazard ratio (HR) of 3.78 (95% confidence interval CI 1.70-8.45) for walking speed limitation compared with people in the lowest score tertile, even after adjusting for socio-demographics, CRFs, cognitive function, and chronic conditions. When investigating the cSVD markers individually, having the highest burden of WMH was associated with a significantly faster decline in walking speed (β coefficient - 0.020; 95% CI -0.035-0.004) and a greater HR of walking speed limitation (HR 2.78; 95% CI 1.31-5.89) compared with having the lowest WMH burden. Similar results were obtained for the highest tertile of PVS (HR 2.13; 95% CI 1.04-4.36). Lacunes were associated with walking speed limitation, but only in men. Having ≥4 CRFs and high WMH volume simultaneously, showed a greater risk of walking speed limitation compared with having ≥4 CRFs and low WMH burden. CRFs did not modify the associations between lacunes or PVS and walking speed.
Combined cSVD markers strongly predict walking speed limitation in healthy older adults, independent of cognitive function, with WMH and PVS being the strongest contributors. Improving cardiovascular health may help to mitigate the negative effects of WMH on future walking speed.
We investigated progression and interrelationships of cerebral small vessel disease (cSVD) markers. This population-based cohort study included 325 participants (age ≥ 60 years) who had repeated ...measures of cSVD markers over 6 years: white-matter hyperintensity (WMH), perivascular spaces (PVS), lacunes, and grey-matter (GM) and ventricular volumes. We found that all cSVD markers, except PVS, progressed faster with increasing age. Regional WMH progressed faster in males and less-educated people (p < 0.05). Each 10-point increment in global WMH score was associated with multi-adjusted hazard ratio of 1.78 (95% CI = 1.50‒2.10) for incident lacunes and multi-adjusted β-coefficients of 0.15 (0.08–0.22), -0.37 (-0.58‒-0.16), and 0.11 (0.03‒0.18) for annual changes of global WMH score, GM volume, and ventricular volume, respectively. The corresponding figures associated with per 10-PVS increment were 1.14 (1.01‒1.28), 0.07 (0.03‒0.11), -0.18 (-0.32‒-0.04), and 0.02 (-0.03‒0.07). Prevalent lacunes were related to multi-adjusted β-coefficients of 0.29 (0.00‒0.58), 0.22 (0.05‒0.38), 0.10 (0.01‒0.18), and -0.93 (-1.83‒-0.03) for annual changes of global, deep, and periventricular WMH scores and GM volume, respectively. These results suggest that cSVD progresses faster in older, male, and less-educated people, and that greater loads of WMH, PVS, and lacunes anticipate faster cSVD progression.
The life's simple 7 approach was proposed to define cardiovascular health (CVH) metrics. We sought to investigate the associations between behavioral, biological, and genetic markers for CVH and ...vascular brain aging in older adults.
This population-based cohort study included participants who had repeated brain MRI measures from 2001 to 2003 to 2007-2010 (i.e., count of perivascular spaces, volumes of white matter hyperintensity WMH and gray matter, and lacunes). At baseline, global, behavioral, and biological CVH metrics were defined and scored following the life's simple 7 approach and categorized into unfavorable, intermediate, and favorable profiles according to tertiles. The metabolic genetic risk score was calculated by counting 15 risk alleles associated with hypertension, diabetes, or dyslipidemia. Data were analyzed using linear mixed-effects and Cox proportional hazards models, adjusting for age, sex, and education.
The study sample consisted of 317 participants (age 60 years or older; 61.8% women). Favorable and intermediate (vs unfavorable) global CVH profiles were related to slower WMH progression, with β-coefficients (95% CI) being -0.019(-0.035-0.002) and -0.018(-0.034-0.001), respectively. Favorable and intermediate (vs unfavorable) biological CVH profiles were significantly related to slower WMH increase only in people aged 60-72 years. CVH profiles were not related to progression of other brain measures. Furthermore, a higher metabolic genetic risk score (range: 6-21) was associated with faster WMH increase (β-coefficient = 0.005; 95% CI: 0.003-0.008). There were statistical interactions of metabolic genetic risk score with global and behavioral CVH profiles on WMH accumulation. A higher metabolic genetic risk score was related to faster WMH accumulation, with β-coefficients being 0.015(0.007-0.023), 0.005(0.001-0.009), and 0.003(-0.001 to 0.006) among people with unfavorable, intermediate, and favorable global CVH profiles, respectively; the corresponding β-coefficients were 0.013(0.006-0.020), 0.006(0.003-0.009), and 0.002(-0.002 to 0.006) among people with unfavorable, intermediate, and favorable behavioral CVH profiles.
Intermediate to favorable global CVH profiles in older adults are associated with slower vascular brain aging. The association of metabolic genetic risk load with accelerated vascular brain aging was evident among people with unfavorable to intermediate, but not favorable, CVH profiles. These findings highlight the importance of adhering to favorable CVH profiles, especially healthy behaviors, in vascular brain health.
Vitamin B12, folate, and sulfur amino acids may be modifiable risk factors for structural brain changes that precede clinical dementia.
To investigate the association of circulating levels of vitamin ...B12, red blood cell folate, and sulfur amino acids with the rate of total brain volume loss and the change in white matter hyperintensity volume as measured by fluid-attenuated inversion recovery in older adults.
The magnetic resonance imaging subsample of the Swedish National Study on Aging and Care in Kungsholmen, a population-based longitudinal study in Stockholm, Sweden, was conducted in 501 participants aged 60 years or older who were free of dementia at baseline. A total of 299 participants underwent repeated structural brain magnetic resonance imaging scans from September 17, 2001, to December 17, 2009.
The rate of brain tissue volume loss and the progression of total white matter hyperintensity volume.
In the multi-adjusted linear mixed models, among 501 participants (300 women 59.9%; mean SD age, 70.9 9.1 years), higher baseline vitamin B12 and holotranscobalamin levels were associated with a decreased rate of total brain volume loss during the study period: for each increase of 1 SD, β (SE) was 0.048 (0.013) for vitamin B12 (P < .001) and 0.040 (0.013) for holotranscobalamin (P = .002). Increased total homocysteine levels were associated with faster rates of total brain volume loss in the whole sample (β SE per 1-SD increase, -0.035 0.015; P = .02) and with the progression of white matter hyperintensity among participants with systolic blood pressure greater than 140 mm Hg (β SE per 1-SD increase, 0.000019 0.00001; P = .047). No longitudinal associations were found for red blood cell folate and other sulfur amino acids.
This study suggests that both vitamin B12 and total homocysteine concentrations may be related to accelerated aging of the brain. Randomized clinical trials are needed to determine the importance of vitamin B12 supplementation on slowing brain aging in older adults.
Dopaminergic neuromodulation is critically important for brain and cognitive integrity. The DRD2/ANKK1 Taq1A polymorphism is associated with striatal dopamine (DA) D2 receptor availability. Some ...previous studies have found that the A allele of the Taq1A polymorphism influences brain structure, but the results are inconsistent, likely due to population heterogeneity and small sample sizes. We investigated the genetic effect on caudate volume in a large sample of older adults without dementia. Results show that A-allele carriers have smaller caudate volume compared to non-carriers in relatively older adults (
n
= 167; Mage = 77.8 years), whereas the genotype did not influence caudate volume in a younger age group (
n
= 220; Mage = 62.8 years). Cognitive performance was not significantly affected by the DRD2 gene. Our findings extend previous observations by showing magnified genetic effects on brain volume in old age, and provide evidence for a link between a DA-related genetic polymorphism and grey matter volume in a brain region within the nigrostriatal dopaminergic pathway.
Introduction
We investigated whether lifelong exposure to stimulating activities (active life, AL) mitigates diabetes‐associated dementia risk and brain aging.
Methods
In the Swedish National Study ...on Aging and Care‐Kungsholmen, 2286 dementia‐free older adults (407 with MRI volumetric measures) were followed over 12 years to detect incident dementia. AL index (low, moderate, high) combined education, work complexity, leisure activities, and social network.
Results
Participants with diabetes and low AL had higher dementia risk (hazard ratio HR = 2.36, 95% confidence interval CI 1.45–3.87) than patients who were diabetes‐free with moderate‐to‐high AL (reference). Dementia risk in participants with diabetes and moderate‐to‐high AL did not differ from the reference. People with diabetes and low AL had the smallest brain volume, but those with diabetes and moderate‐to‐high AL exhibited total brain and gray‐matter volumes that were similar to those of diabetes‐free participants. AL did not modify the diabetes microvascular lesions association.
Discussion
AL could mitigate the deleterious impact of diabetes on dementia, potentially by limiting the loss of brain tissue volume.
Background
Brain iron overload is linked to brain deterioration, and cognitive and motor impairment in neurodegenerative disorders and normal aging. Mutations in the HFE gene are associated with iron ...dyshomeostasis and are risk factors for peripheral iron overload. However, links to brain iron load and cognition are less consistent and data are scarce.
Aims and methods
Using quantitative susceptibility mapping with magnetic resonance imaging, we investigated whether C282Y and H63D contributed to aging‐related increases in brain iron load and lower cognitive and motor performance in 208 healthy individuals aged 20‐79 years. We also assessed the modulatory effects of HFE mutations on associations between performance and brain iron load, as well as peripheral iron metabolism.
Results
Independent of age, carriers of either C282Y and/or H63D (HFE‐pos group, n = 66) showed a higher load of iron in putamen than non‐carriers (HFE‐neg group, n = 142), as well as higher transferrin saturation and lower transferrin and transferrin receptors in blood. In the HFE‐neg group, higher putaminal iron was associated with lower working memory. In the HFE‐pos group, higher putaminal iron was instead linked to higher executive function, and lower plasma transferrin was related to higher episodic memory. Iron‐performance associations were modest albeit reliable.
Conclusion
Our findings suggest that HFE status is characterized by higher regional brain iron load across adulthood, and support the presence of a modulatory effect of HFE status on the relationships between iron load and cognition. Future studies in healthy individuals are needed to confirm the reported patterns.
This study investigated the contribution of genetic polymorphisms in the HFE gene (C282Y and H63D) on blood and brain iron load, and their relationships with cognition, in a healthy sample of adults. The findings indicated that carriers of C282Y and/or H63D displayed higher iron load in putamen and higher transferrin saturation in blood. Results further suggested that in carriers, higher iron load may be beneficial for cognitive performance, independent of age.
Cerebral small vessel disease, as a potential mechanism underlying the association between atrial fibrillation (AF) and dementia, remains poorly investigated. In this cohort study, we sought to ...examine the association between AF and cerebral small vessel disease markers among older adults.
Data on 336 participants (age ≥60 years, mean 70.2 years; 60.2% women) free of dementia, disability, and cerebral infarcts were derived from the population-based Swedish National Study on Aging and Care in Kungsholmen. Structural brain magnetic resonance imaging examinations were performed at baseline (2001–2004) and follow-ups (2004–2007 and 2007–2010). Magnetic resonance imaging markers of cerebral small vessel disease included perivascular spaces, lacunes, and volumes of white matter hyperintensities, lateral ventricles, and total brain tissue. AF was assessed at baseline and follow-ups through clinical examinations, electrocardiogram, and medical records. Data were analyzed using linear mixed-effects models.
At baseline, 18 persons (5.4%) were identified to have prevalent AF and 17 (5.6%) developed incident AF over the 6-year follow-up. After multivariable adjustment, AF was significantly associated with a faster annual increase in white matter hyperintensities volume (β coefficient=0.45 95% CI, 0.04–0.86) and lateral ventricular volume (0.58 0.13–1.02). There was no significant association of AF with annual changes in perivascular spaces number (β coefficient=0.53 95% CI, −0.27 to 1.34) or lacune number (−0.01 −0.07 to 0.05).
Independent of cerebral infarcts, AF is associated with accelerated progression of white matter lesions and ventricular enlargement among older adults.
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