Structural Brain Integrity In Midlife Research Articles

Association of childhood lead exposure with MRI measurements of structural brain integrity in midlife

BACKGROUND AND AIM: Childhood lead exposure has been linked to disrupted brain development, but long-term consequences for structural brain integrity are unknown. This study tested the hypothesis that childhood lead exposure is associated with magnetic resonance imaging (MRI) measurements of lower structural integrity of the brain in midlife. METHODS: Hypotheses tested in the Dunedin Study, a New Zealand-based population-representative 1972-1973 birth cohort (N=564 analytic sample) followed to age 45 years. Childhood blood-lead levels measured at age 11 years were combined with MRI-measures of brain integrity at age 45 years, including gray matter (cortical thickness, surface area, hippocampal volume), white matter (white matter hyperintensities, fractional anisotropy), and brainAGE, a composite index of the gap between chronological age and a machine-learning algorithm-estimated brain age. Age-45 cognitive function was also assessed, objectively via the Wechsler Adult Intelligence Scale–IV and subjectively via informant and self-reports. RESULTS:Mean(SD) age-11 blood-lead level was 10.99(4.63)µg/dL. After adjusting for covariates, each 5µg/dL higher childhood blood-lead level was significantly associated with 1.19-cm2 smaller cortical surface area (95%CI:-2.35,-0.02, P=.05), 0.10-cm3 smaller hippocampal volume (95%CI:-0.17,-0.03, P=.006), lower global fractional anisotropy (b=-0.12, 95%CI:-0.24,-0.01, P=.04), and 0.77-years older brainAGE (95%CI:0.02, 1.51, P=.05). There were no statistically significant associations between blood-lead level and log-transformed white matter hyperintensity volume (b=0.05 log mm3, 95%CI:-0.02, 0.13, P=.17) or mean cortical thickness (b=-0.004 mm, 95%CI:-0.012, 0.004, P=.39). Each 5µg/dL higher childhood blood-lead level was significantly associated with a 2.07-point lower score (95%CI:-3.39,-0.74, P=.002) in age-45 IQ, and a 0.12-point higher score (95%CI:0.01, 0.23, P=.03) on informant-rated cognitive problems. There was no statistically significant association between childhood blood-lead levels and self-reported cognitive problems (b=-0.02 points, 95%CI: -0.10, 0.07, P=.68). CONCLUSIONS:In this four-decade study, higher childhood blood-lead level was associated with lower structural brain integrity in midlife. Childhood lead exposure may have long-term consequences for adult brain health. KEYWORDS: Heavy metals, Neurodegenerative outcomes, Environmental epidemiology

Better cardiovascular fitness is associated with better structural brain integrity in midlife: A population‐representative birth cohort study

AbstractBackgroundImproving cardiovascular fitness has been promoted as a promising nonpharmacological strategy for buffering against age‐related cognitive decline and mitigating risk for Alzheimer’s disease and related dementia (ADRD). These beneficial effects may be related to the capacity for improved cardiovascular fitness to stave off age‐related brain atrophy. However, there is evidence that some neurological benefits associated with adult cardiovascular fitness may be better explained by early childhood factors—referred to as neuroselection—rather than any active neuroprotective effects of fitness on the brain.MethodData from 875 participants from the population‐representative Dunedin Study were utilized to investigate associations between cardiovascular fitness (VO2Max) at age 45, changes in cardiovascular fitness across adulthood, and structural brain integrity (cortical thickness, surface area, and subcortical grey matter volume) at age 45. Critically, the potential confounding effects of childhood IQ on any observed associations in midlife were evaluated in order to disentangle potential neuroselective from neuroprotective effects.ResultBetter VO2Max at age 45 was associated with thicker cortex in frontal and temporal lobes (βs:0.14 to 0.25, Figure 1b) and smaller hippocampal fissure volumes at age 45 (β=‐0.18). Higher rates of decline in VO2max were associated with lower total (β=‐0.11) and distributed regional (βs:‐0.11 to ‐0.19, Figure 2b) surface area at age 45. These associations were unaffected by the inclusion of childhood IQ in the analyses.ConclusionBetter midlife cardiovascular fitness may offer neuroprotective effects on brain structure, which may in turn mitigate ADRD risk and buffer against cognitive decline.

Association of Childhood Lead Exposure With MRI Measurements of Structural Brain Integrity in Midlife

Childhood lead exposure has been linked to disrupted brain development, but long-term consequences for structural brain integrity are unknown. To test the hypothesis that childhood lead exposure is associated with magnetic resonance imaging (MRI) measurements of lower structural integrity of the brain in midlife. The Dunedin Study followed a population-representative 1972-1973 birth cohort in New Zealand (N = 564 analytic sample) to age 45 years (until April 2019). Childhood blood lead levels measured at age 11 years. Structural brain integrity at age 45 years assessed via MRI (primary outcomes): gray matter (cortical thickness, surface area, hippocampal volume), white matter (white matter hyperintensities, fractional anisotropy [theoretical range, 0 {diffusion is perfectly isotropic} to 100 {diffusion is perfectly anisotropic}]), and the Brain Age Gap Estimation (BrainAGE), a composite index of the gap between chronological age and a machine learning algorithm-estimated brain age (0 indicates a brain age equivalent to chronological age; positive and negative values represent an older and younger brain age, respectively). Cognitive function at age 45 years was assessed objectively via the Wechsler Adult Intelligence Scale IV (IQ range, 40-160, standardized to a mean of 100 [SD, 15]) and subjectively via informant and self-reports (z-score units; scale mean, 0 [SD, 1]). Of 1037 original participants, 997 were alive at age 45 years, of whom 564 (57%) had received lead testing at age 11 years (302 [54%] male) (median follow-up, 34 [interquartile range, 33.7-34.7] years). Mean blood lead level at age 11 years was 10.99 (SD, 4.63) μg/dL. After adjusting for covariates, each 5-μg/dL higher childhood blood lead level was significantly associated with 1.19-cm2 smaller cortical surface area (95% CI, -2.35 to -0.02 cm2; P = .05), 0.10-cm3 smaller hippocampal volume (95% CI, -0.17 to -0.03 cm3; P = .006), lower global fractional anisotropy (b = -0.12; 95% CI, -0.24 to -0.01; P = .04), and a BrainAGE index 0.77 years older (95% CI, 0.02-1.51 years; P = .05) at age 45 years. There were no statistically significant associations between blood lead level and log-transformed white matter hyperintensity volume (b = 0.05 log mm3; 95% CI, -0.02 to 0.13 log mm3; P = .17) or mean cortical thickness (b = -0.004 mm; 95% CI, -0.012 to 0.004 mm; P = .39). Each 5-μg/dL higher childhood blood lead level was significantly associated with a 2.07-point lower IQ score at age 45 years (95% CI, -3.39 to -0.74; P = .002) and a 0.12-point higher score on informant-rated cognitive problems (95% CI, 0.01-0.23; P = .03). There was no statistically significant association between childhood blood lead levels and self-reported cognitive problems (b = -0.02 points; 95% CI, -0.10 to 0.07; P = .68). In this longitudinal cohort study with a median 34-year follow-up, higher childhood blood lead level was associated with differences in some MRI measures of brain structure that suggested lower structural brain integrity in midlife. Because of the large number of statistical comparisons, some findings may represent type I error.