Total Gray Matter Volume Research Articles

Modeling the development of cognitive reserve in children: A residual index approach.

To model cognitive reserve (CR) longitudinally in a neurodiverse pediatric sample using a residual index approach, and to test the criterion and construct validity of this index. Participants were N = 115 children aged 9.5-13 years at baseline (MAge = 10.48 years, SDAge = 0.61), and n = 43 (37.4%) met criteria for ADHD. The CR index represented variance in Matrix Reasoning scores from the WASI that was unexplained by MRI-based brain variables (bilateral hippocampal volumes, total gray matter volumes, and total white matter hypointensity volumes) or demographics (age and sex). At baseline, the CR index predicted math computation ability (estimate = 0.50, SE = 0.07, p < .001), and word reading ability (estimate = 0.26, SE = 0.10, p = .012). Longitudinally, change in CR over time was not associated with change in math computation ability (estimate = -0.02, SE = 0.03, p < .513), but did predict change in word reading ability (estimate = 0.10, SE = 0.03, p < .001). Change in CR was also found to moderate the relationship between change in word reading ability and white matter hypointensity volume (estimate = 0.10, SE = 0.05, p = .045). Evidence for the criterion validity of this CR index is encouraging, but somewhat mixed, while construct validity was evidenced through interaction between CR, brain, and word reading ability. Future research would benefit from optimization of the CR index through careful selection of brain variables for a pediatric sample.

Prenatal exposure to common plasticizers: a longitudinal study on phthalates, brain volumetric measures, and IQ in youth.

Exposure to phthalates, used as plasticizers and solvents in consumer products, is ubiquitous. Despite growing concerns regarding their neurotoxicity, brain differences associated with gestational exposure to phthalates are understudied. We included 775 mother-child pairs from Generation R, a population-based pediatric neuroimaging study with prenatal recruitment, who had data on maternal gestational phthalate levels and T1-weighted magnetic resonance imaging in children at age 10 years. Maternal urinary concentrations of phthalate metabolites were measured at early, mid-, and late pregnancy. Child IQ was assessed at age 14 years. We investigated the extent to which prenatal exposure to phthalates is associated with brain volumetric measures and whether brain structural measures mediate the association of prenatal phthalate exposure with IQ. We found that higher maternal concentrations of monoethyl phthalate (mEP, averaged across pregnancy) were associated with smaller total gray matter volumes in offspring at age 10 years (β per log10 increase in creatinine adjusted mEP = -10.7, 95%CI: -18.12, -3.28). Total gray matter volumes partially mediated the association between higher maternal mEP and lower child IQ (β for mediated path =-0.31, 95%CI: -0.62, 0.01, p = 0.05, proportion mediated = 18%). An association of higher monoisobutyl phthalate (mIBP) and smaller cerebral white matter volumes was present only in girls, with cerebral white matter volumes mediating the association between higher maternal mIBP and lower IQ in girls. Our findings suggest the global impact of prenatal phthalate exposure on brain volumetric measures that extends into adolescence and underlies less optimal cognitive development.

The effects of environmental factors associated with childhood urbanicity on brain structure and cognition.

Urbanization is a trend lasting for more than one century worldwide. Four hundred ninety male and female adult Chinese Han participants with different urban and rural childhoods were included in this study. Early-life urban environment was found benefit for total grey matter volume (GMV), dorsolateral prefrontal cortex (DLPFC) GMV, temporal pole (TP) GMV and cognition function, and negatively correlated with medial prefrontal cortex (MPFC) GMV. Regression analysis showed that maternal education was a protective factor for total and DLPFC GMVs, while having siblings was better for MPFC GMV. Total, DLPFC and TP GMVs acts mediation effects between childhood urbanicity and different cognitive domains. These findings may suggest some pros and cons on brain structure associated with childhood urbanicity and related environmental factors.

Association of Kidney Function With Dementia and Structural Brain Differences: A Large Population-Based Cohort Study.

The association between kidney function and dementia risk and the mechanisms underlying this relationship remain unclear. Within the UK Biobank, 191 970 dementia-free participants aged ≥60 (mean age: 64.1 ± 2.9 years) were followed for 16 years to detect incident dementia. Serum creatinine and Cystatin C were measured at baseline to calculate estimated glomerular filtration rate (eGFR, mL/min/1.73 m2). Kidney function was categorized as normal (eGFR ≥ 90), mildly impaired (60 ≤ eGFR < 90), or moderately to severely impaired (eGFR < 60). Dementia was assessed based on self-reported medical history and medical records. During the follow-up, a subsample of 12 637 participants underwent brain MRI scans. Volumes of total brain, gray matter, white matter, hippocampus, and white matter hyperintensities were assessed. Over the follow-up, 5 327 (2.8%) participants developed dementia. Compared to normal kidney function, there was an increased risk of dementia with moderate to severely impaired kidney function (hazard ratio = 1.53, 95% confidence interval [CI]: 1.32-1.76) but not mildly impaired kidney function. In Laplace regression, dementia onset among people with moderate to severely impaired kidney function occurred 1.53 (95% CI: 0.98-2.08) years earlier than those with normal kidney function. Moderate to severely impaired kidney function was related to significantly lower gray matter volume (β = -0.11, 95% CI: -0.19 to -0.03), but not to other brain magnetic resonance imaging measures. Impaired kidney function is associated with about 50% increased risk of dementia and anticipates dementia onset by more than 1.5 years. Brain neurodegeneration may underlie the kidney function-dementia association.

Associations between polygenic risk scores and accelerated brain ageing in smokers.

Smoking contributes to a variety of neurodegenerative diseases and neurobiological abnormalities, suggesting that smoking is associated with accelerated brain aging. However, the neurobiological mechanisms affected by smoking, and whether they are genetically influenced, remain to be investigated. Using structural magnetic resonance imaging data from the UK Biobank (n = 33 293), a brain age predictor was trained on non-smoking healthy groups and tested on smokers to obtain the BrainAge Gap (BAG). The cumulative effect of multiple common genetic variants associated with smoking was then calculated to acquire a polygenic risk score (PRS). The relationship between PRS, BAG, total gray matter volume (tGMV), and smoking parameters was explored and further genes included in the PRS were annotated to identify potential molecular mechanisms affected by smoking. The BrainAge in smokers was predicted with very high accuracy (r = 0.725, MAE = 4.16). Smokers had a greater BAG (Cohen's d = 0.074, p < 0.0001) and higher PRS (Cohen's d = 0.63, p < 0.0001) than non-smokers. A higher PRS was associated with increased amount of smoking, mediated by BAG and tGMV. Several neurotransmitters and ion channel pathways were enriched in the group of smoking-related genes involved in addiction, brain synaptic plasticity, and some neurological disorders. By using a simplified single indicator of the entire brain (BAG) in combination with the PRS, this study highlights the greater BAG in smokers and its linkage with genes and smoking behavior, providing insight into the neurobiological underpinnings and potential features of smoking-related aging.

Reduced mammillary body volume in individuals with a schizophrenia diagnosis: an analysis of the COBRE data set

While the frontal cortices and medial temporal lobe are well associated with schizophrenia, the involvement of wider limbic areas is less clear. The mammillary bodies are important for both complex memory formation and anxiety and are implicated in several neurological disorders that present with memory impairments. However, little is known about their role in schizophrenia. Post-mortem studies have reported a loss of neurons in the mammillary bodies but there are also reports of increased mammillary body volume. The findings from in vivo MRI studies have also been mixed, but studies have typically only involved small sample sizes. To address this, we acquired mammillary body volumes from the open-source COBRE dataset, where we were able to manually measure the mammillary bodies in 72 individuals with a schizophrenia diagnosis and 74 controls. Participant age ranged from 18 to 65. We found the mammillary bodies to be smaller in the patient group, across both hemispheres, after accounting for the effects of total brain volume and gender. Hippocampal volumes, but not subiculum or total grey matter volumes, were also significantly lower in patients. Given the importance of the mammillary bodies for both memory and anxiety, this atrophy could contribute to the symptomology in schizophrenia.

Long-term neurodevelopmental outcome and serial cerebral magnetic resonance imaging assessment in Fontan patients at school age.

Children with univentricular congenital heart disease undergoing staged surgical palliation are at risk for impaired neurodevelopmental (ND) outcome. Little is known about the long-term effects on brain growth until school age. In a prospective two-centre study, consecutive patients undergoing stage I (Hybrid or Norwood) to stage III (Fontan procedure) were evaluated by 2 serial cerebral magnetic resonance imaging examinations, somatic growth and ND testing before Fontan procedure at 2 years of age (Bayley-III) and after Fontan at 6-8 years of age (Wechsler Intelligence Scale for Children-third edition). Magnetic resonance imaging findings were compared with 8 healthy controls. Medical and sociodemographic characteristics were documented and related to cerebral and ND findings. We examined 33 children (16 female) at a mean age of 2.3 (0.35) and 6.8 (± 0.7) years. The mean Bayley-III cognitive scales were 99.1 (9.9), language scales 98.4 (11.9) and motor scales 98.5 (13.8) at the first examination. Follow-up at school age showed a mean total IQ of 86.7 (13.6). The rate of structural brain lesions increased from 39% at 2 years to 58% at school age. Bayley-III language scale (P = 0.021) and mean Wechsler Intelligence Scale for Children-third edition (P = 0.019) were lower in children with pathological MR findings. Total brain volume (P < 0.001), total grey matter volume (P = 0.002), deep grey matter volume (P = 0.001) and white matter volume (P < 0.001) were smaller in patients compared to age- and gender-matched healthy controls. Smaller brain volumes and structural brain lesions in complex congenital heart defect patients at school age are associated with impaired ND outcome. For the evaluation of predictive surgical or clinical factors, larger multicentre studies are needed.

Associations of Glucose Metabolism Status with Brain Macrostructure and Microstructure: Findings from the UK Biobank.

Evidence linking glucose metabolism status with brain macro- and microstructure is limited and inconsistent. We aim to investigate the associations of glucose metabolism status with brain macrostructure and microstructure, including brain volumes, subcortical gray matter volumes, and white matter microstructural metrics. This study enrolled 29 251 participants from the UK Biobank. Glucose metabolism status was classified into normal glucose metabolism (NGM), prediabetes, type 2 diabetes (T2D) with HbA1c <7%, and T2D with HbA1c ≥7%. Brain macrostructural metrics included volumes of total and subcortical gray matter, white matter, white matter hyperintensity (WMH), cerebrospinal fluid, and brain stem. Brain microstructural metrics included fractional anisotropy (FA) and mean diffusivity in white matter tracts. Multivariable linear regression models were used to estimate β values and 95% CI. After multivariable adjustment including demographic and lifestyle factors, medical history, and total intracranial volume, those with prediabetes had smaller total and subcortical gray matter volumes than participants with NGM, while atrophy of total and subcortical gray matter was more pronounced in those with T2D (all P trend < .05). Moreover, participants with T2D had larger volumes of white matter and WMH (both P trend < .05). For brain microstructure, participants with prediabetes had lower FA values in commissural fibers (β -0.04; 95% CI -0.08, -0.003). Global and tract-specific microstructural abnormalities of white matter were observed in participants with T2D, especially for T2D with HbA1c ≥ 7% (all P trend < .05), except for FA values in projection fibers. These findings suggest that interventions for hyperglycemia at an earlier stage may help protect brain health.

Differential response to donepezil in MRI subtypes of mild cognitive impairment

BackgroundDonepezil is an approved therapy for the treatment of Alzheimer’s disease (AD). Results across clinical trials have been inconsistent, which may be explained by design-methodological issues, the pathophysiological heterogeneity of AD, and diversity of included study participants. We investigated whether response to donepezil differs in mild cognitive impaired (MCI) individuals demonstrating different magnetic resonance imaging (MRI) subtypes.MethodsFrom the Hippocampus Study double-blind, randomized clinical trial, we included 173 MCI individuals (donepezil = 83; placebo = 90) with structural MRI data, at baseline and at clinical follow-up assessments (6–12-month). Efficacy outcomes were the annualized percentage change (APC) in hippocampal, ventricular, and total grey matter volumes, as well as in the AD cortical thickness signature. Participants were classified into MRI subtypes as typical AD, limbic-predominant, hippocampal-sparing, or minimal atrophy at baseline. We primarily applied a subtyping approach based on continuous scale of two subtyping dimensions. We also used the conventional categorical subtyping approach for comparison.ResultsDonepezil-treated MCI individuals showed slower atrophy rates compared to the placebo group, but only if they belonged to the minimal atrophy or hippocampal-sparing subtypes. Importantly, only the continuous subtyping approach, but not the conventional categorical approach, captured this differential response.ConclusionsOur data suggest that individuals with MCI, with hippocampal-sparing or minimal atrophy subtype, may have improved benefit from donepezil, as compared with MCI individuals with typical or limbic-predominant patterns of atrophy. The newly proposed continuous subtyping approach may have advantages compared to the conventional categorical approach. Future research is warranted to demonstrate the potential of subtype stratification for disease prognosis and response to treatment.Trial registrationClinicalTrial.gov NCT00403520. Submission Date: November 21, 2006.

Longitudinal Gray Matter Trajectories in Pediatric Mild Traumatic Brain Injury.

This prospective, longitudinal cohort study examined trajectories of brain gray matter macrostructure after pediatric mild traumatic brain injury (mTBI). Children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) were recruited from 5 pediatric emergency departments. Reliable change between preinjury and 1 month postinjury symptom ratings was used to classify mTBI with or without persistent symptoms. Children completed postacute (2-33 days) and/or chronic (3 or 6 months) postinjury T1-weighted MRI, from which macrostructural metrics were derived using automated segmentation. Linear mixed-effects models were used, with multiple comparisons correction. Groups (N = 623; 407 mTBI/216 OI; 59% male; age mean = 12.03, SD = 2.38 years) did not differ in total brain, white, or gray matter volumes or regional subcortical gray matter volumes. However, time postinjury, age at injury, and biological sex-moderated differences among symptom groups in cortical thickness of the angular gyrus, basal forebrain, calcarine cortex, gyrus rectus, medial and posterior orbital gyrus, and the subcallosal area all corrected p < 0.05. Gray matter macrostructural metrics did not differ between groups postacutely. However, cortical thinning emerged chronically after mTBI relative to OI in the angular gyrus in older children (d [95% confidence interval] = -0.61 [-1.15 to -0.08]); and in the basal forebrain (-0.47 [-0.94 to -0.01]), subcallosal area (-0.55 [-1.01 to -0.08]), and the posterior orbital gyrus (-0.55 [-1.02 to -0.08]) in females. Cortical thinning was demonstrated for frontal and occipital regions 3 months postinjury in males with mTBI with persistent symptoms vs without persistent symptoms (-0.80 [-1.55 to -0.05] to -0.83 [-1.56 to -0.10]) and 6 months postinjury in females and younger children with mTBI with persistent symptoms relative to mTBI without persistent symptoms and OI (-1.42 [-2.29 to -0.45] to -0.91 [-1.81 to -0.01]). These findings signal little diagnostic and prognostic utility of postacute gray matter macrostructure in pediatric mTBI. However, mTBI altered the typical course of cortical gray matter thinning up to 6 months postinjury, even after symptoms typically abate in most children. Collapsing across symptom status obscured the neurobiological heterogeneity of discrete clinical outcomes after pediatric mTBI. The results illustrate the need to examine neurobiology in relation to clinical outcomes and within a neurodevelopmental framework.

Lifestyle-related risk factors and their cumulative associations with hippocampal and total grey matter volume across the adult lifespan: A pooled analysis in the European Lifebrain consortium

BackgroundLifestyle-related risk factors, such as obesity, physical inactivity, short sleep, smoking and alcohol use, have been associated with low hippocampal and total grey matter volumes (GMV). However, these risk factors have mostly been assessed as separate factors, leaving it unknown if variance explained by these factors is overlapping or additive. We investigated associations of five lifestyle-related factors separately and cumulatively with hippocampal and total GMV, pooled across eight European cohorts. MethodsWe included 3838 participants aged 18–90 years from eight cohorts of the European Lifebrain consortium. Using individual person data, we performed cross-sectional meta-analyses on associations of presence of lifestyle-related risk factors separately (overweight/obesity, physical inactivity, short sleep, smoking, high alcohol use) as well as a cumulative unhealthy lifestyle score (counting the number of present lifestyle-related risk factors) with FreeSurfer-derived hippocampal volume and total GMV. Lifestyle-related risk factors were defined according to public health guidelines. ResultsHigh alcohol use was associated with lower hippocampal volume (r = −0.10, p = 0.021), and overweight/obesity with lower total GMV (r = −0.09, p = 0.001). Other lifestyle-related risk factors were not significantly associated with hippocampal volume or GMV. The cumulative unhealthy lifestyle score was negatively associated with total GMV (r = −0.08, p = 0.001), but not hippocampal volume (r = −0.01, p = 0.625). ConclusionsThis large pooled study confirmed the negative association of some lifestyle-related risk factors with hippocampal volume and GMV, although with small effect sizes. Lifestyle factors should not be seen in isolation as there is evidence that having multiple unhealthy lifestyle factors is associated with a linear reduction in overall brain volume.

Circulating extracellular vesicles of neurovascular origin are elevated in women with severe preeclampsia years after their affected pregnancies

AbstractBackgroundPreeclampsia (PE), a pregnancy specific hypertensive disorder, has been associated with elevated risk for strokes, cognitive decline, and smaller brain volumes later in life. As severe PE has been associated with the highest risks for cerebrovascular disease, we hypothesized that circulating extracellular vesicles (EVs) of neurovascular origin will be detectable in women years after severe PE as a marker of persistent neurovascular damage and amyloid‐β.MethodA cohort of 40 women with histories of normotensive pregnancies (control group) and age‐ and parity‐matched to 40 women with history of mild (n = 33) and severe (n = 7) PE were identified using the Rochester Epidemiology Project. Diagnosis of severe PE was ascertained based on clinical criteria (Table). While none of the women had any major cardiovascular events, our previous study of this cohort has demonstrated that total gray matter volumes were smaller in women with a history of preeclampsia and late‐life hypertension compared with the other groups. Blood‐borne EVs derived from neurovascular cellular activation were determined by standardized digital flow cytometry. Plasma concentration of amyloid‐β was measured by ELISA. Differences among the groups were tested by ANOVA, with the least difference test for pos hoc analysis. The association between EVs and MRI brain imaging was assessed by Pearson correlation coefficient.ResultWomen with history of severe PE had a significantly higher concentration of amyloid‐β carrying EVs compared to controls (p = 0.003). EVs positive for the markers of blood‐brain barrier‐ endothelial damage (LDL‐R) and inflammatory coagulation pathway activator (tissue factor), were significantly higher in women with history of severe PE compared to controls (p = 0.008 and p = 0.002, respectively), as well as to the women with history of mild PE. Plasma concentration of total amyloid‐β was also significantly greater in women with history of severe vs. mild PE (p = 0.037) (Table). The number of tissue factor positive EVs was negatively correlated with total gray matter volume (cm3) (p&lt;0.05).ConclusionWomen with a history of severe PE demonstrate elevated levels of markers of neuroinflammation and neurovascular damage, as well as greater amyloid‐β secretion. Excessive inflammation may contribute to previously described brain atrophy in these women.

Association of motor function with cognitive trajectories, risk of mild cognitive impairment, and structural brain differences

AbstractBackgroundThe impact of motor function (MF) on cognitive trajectories and mild cognitive impairment (MCI) remains unclear. This study aimed to examine the association of MF with cognitive trajectories, risk of MCI, and structural brain differences on magnetic resonance imaging (MRI).MethodWithin the Rush Memory and Aging Project, 1,216 cognitively intact participants (mean age: 78.60±7.25 years) were followed for up to 22 years. Baseline global MF was assessed by averaging the z‐scores of 10 motor tests and categorizing these scores tertiles (low middle, and high). Global and domain‐specific cognitive functions – including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed – were assessed annually through 19 cognitive tests. Incident MCI was detected and diagnosed based on standard criteria. A subsample (n = 284) underwent brain MRI and regional structural brain volumes were measured. Data were analyzed using linear mixed‐effects models, Cox regression, and linear regression.ResultAt baseline, global MF scores ranged from 0.46 to 1.82 (mean score: 1.06 ± 0.22). During the follow‐up (median, 6.98 years; interquartile range, 3.08‐10.75 years), 553 participants (45.48%) developed MCI. Compared to participants with high MF, those with low MF had faster decline in global cognition (β = ‐0.05, 95% confidence interval [CI]: ‐0.06 to ‐0.03), episodic memory (β = ‐0.05, 95% CI: ‐0.07 to ‐0.03), semantic memory (β = ‐0.04, 95% CI: ‐0.05 to ‐0.02), working memory (β = ‐0.04, 95% CI: ‐0.05 to ‐0.03), visuospatial ability (β = ‐0.03, 95% CI: ‐0.04 to ‐0.02), and perceptual speed (β = ‐0.04, 95% CI: ‐0.06 to ‐0.03) over the follow‐up. The multi‐adjusted hazard ratio (95% CI) of MCI was 1.84 (1.41 to 2.42) for the lowest MF tertile compared to the highest. Furthermore, the low MF was related to a significantly greater volume of white matter hyperintensities (β = 0.16, 95% CI: 0.01 to 0.32), but not total brain, white matter, or gray matter volumes (all P &gt;0.05).ConclusionLow MF is associated with faster cognitive decline (including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed) and a moderately increased risk of MCI. Vascular pathologies might play an important role in the MF‐MCI association.

Brain neural synchronization mechanisms are affected by aging in cognitively unimpaired seniors and patients with Alzheimer’s disease and mild cognitive impairment

AbstractBackgroundThe resting state eyes‐closed electroencephalographic (rsEEG) alpha (8‐12 Hz) rhythms reflect cortical neural synchronization mechanisms underpinning the inhibition of sensory, cognitive, and motor areas in parietal, temporal, and occipital cortex during a condition of low vigilance. Here we tested the hypothesis that age may diversely affect rsEEG alpha (8‐12 Hz) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer’s disease and mild cognitive impairment (ADMCI).MethodClinical, magnetic resonance imaging (MRI) and rsEEG datasets in 63 ADMCI and 60 Nold individuals were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands as well as fixed beta (14‐30 Hz) and gamma (30‐40 Hz) bands. Each group was stratified into three subgroups based on age ranges (i.e., tertiles).ResultAs compared to the younger Nold subgroups, the older one showed greater reductions in the rsEEG alpha rhythms with major topographical effects in posterior regions (Figure 1). On the contrary, in relation to the younger ADMCI subgroups, the older one displayed lesser reduction in those rhythms (Figure 1). Furthermore, a decrease in the total grey matter (GM) volume and total cortical thickness as well as an increase in the white matter (WM) hypointensity were found in the older ADMCI subgroups compared to the younger ADMCI subgroups (Figure 2).ConclusionThe results of the present study suggest that in Nold seniors, the aging factor may significantly affect neurophysiological brain neural synchronization mechanisms underpinning the generation of dominant rsEEG alpha rhythms. In contrast, rsEEG alpha rhythms in ADMCI patients may be more affected by the disease variants, with more deleterious effects observed in early‐ than the late‐onset ADMCI patients. In the ADMCI patients, the mere effects of the aging factor may be hidden by dysfunctions in subcortical structures, including the cholinergic basal forebrain and thalamus.

Dietary pattern and brain structure among young adults

AbstractBackgroundEnvironmental factors, such as nutrition, influence brain physiology and health throughout the life course. While research has focused on the extremes of the age spectrum, less is known about early adulthood, yet a critical period for the consolidation of brain maturation and the building of adult behaviors. Nutrition may impact late maturational changes in the post‐adolescent brain and contribute to the degree of brain reserve that minimizes the risk to develop dementia. We took advantage of a large sample of young adults to evaluate the association of dietary behavior with brain structure characteristics.MethodThis cross‐sectional study included 1721 university students (18‐35 years‐old) from the French i‐Share cohort, who underwent brain MRI. A 12‐item online Food Frequency Questionnaire was used to evaluate consumption in major food groups and to determine dietary patterns from Principal Component Analysis (PCA). Multivariable‐adjusted linear regressions were used to estimate the association of PCA scores with brain structure (cortical thickness and surface area, grey matter and white matter volumes, diffusion parameters).ResultThe first PCA component (explained variance, 17%) contrasted a healthy diet (higher fruit and vegetable intakes) to a poor diet (higher fast food, sugary drink and snack consumptions). In models adjusted for total intracranial volume, age, sex, physical activity, body mass index, alcohol and tobacco consumptions, a higher PCA score (reflecting healthier diet) was associated with lower total gray matter volume (β for 1 point score = –0.17 [95%CI, –0.31; –0.03] cm3), in various brain areas (Figure). Healthy diet was also associated with lower global white matter volume (β = –0.18 [–0.32; –0.03] cm3). No association was found with diffusion tensor imaging, and neurite orientation dispersion and density imaging metrics in the white matter.ConclusionIn this large sample of young adults, healthier diet was associated with lower brain volumes, independent of multiple potential confounders. Gray matter volume loss during post‐adolescence is a marker of brain maturation; thus, environmental factors emphasizing this loss may benefit maturation. Our results raise the hypothesis that a healthy diet may favor and a poor diet may hamper brain maturation; an assumption which deserves further investigation in other populations.

Mediterranean diet and longitudinal change of white matter hyperintensity in cognitively intact young and older adults

AbstractBackgroundA healthy dietary pattern, Mediterranean diet (MeDi), has been reported to be associated with better brain and cognition. White matter hyperintensities (WMHs), seen in brain magnetic resonance imaging, are considered to be due to cerebral small vessel diseases and have been shown to predict faster cognitive decline in older adults. However, current evidence on the association between MeDi and WMH is inconsistent and longitudinal data are scarce. This study aims to examine whether better adherence to MeDi is associated with less accumulation of WMH over time.MethodThis longitudinal study was conducted among 183 cognitively intact adults aged 20‐80 years. MeDi was calculated from dietary data assessed by a self‐reported food frequency questionnaire, ranging from 0‐55, with a higher score indicating better adherence. WMH was assessed by 3T MRI, and log‐transformed prior to analyses. A one‐sample T‐test was used to examine if WMH burden increased from baseline to follow‐up over an average of five years. Multivariable linear regression was used to estimate the effect of MeDi on the change in WMH. Covariates included age, gender, race/ethnicity, education, IQ, follow‐up interval, caloric intake, baseline WMH, baseline total gray matter volume, and baseline mean cortical thickness. Moderation effects by age (young: &lt;43, middle‐aged: 43‐65, and older: ≥65 years), sex, and race/ethnicity (non‐Hispanic White and other, non‐Hispanic Black, and Hispanic) were examined, followed by stratification analyses.ResultAmong all participants, WMH increased from baseline to follow‐up (mean difference [follow‐up‐baseline][standard error(SE)] = 0.31[0.04], p&lt;0.001). A higher MeDi was associated with less increase of WMH (β[SE] = ‐0.014[0.006], p = 0.034), adjusting by all covariates. The association between MeDi and WMH change was moderated by age group (young group as the reference, p‐interaction[middle‐aged*MeDi] = 0.024, p‐interaction[older*MeDi] = 0.017), adjusting by follow‐up interval: the association was observed among the young group (β[SE] = ‐0.038[0.010], p&lt;0.001), but not among the middle‐aged ((β[SE] = ‐0.002[0.013, p = 0.872]) or the older group ((β[SE] = ‐0.002[0.009], p = 0.836). No significant moderation effects by sex or race/ethnicity were found, adjusting by age and follow‐up interval.ConclusionBetter adherence to MeDi was associated with reduced increase of WMH over time. Following a healthy diet, especially at an early age, may help maintain a healthy brain.

Brain reserve is associated with cognition in AD and MCI patients with different vascualr risk factors status

AbstractBackgroundDementia due to Alzheimer’s disease (AD) is the major type of dementias in the world. In addition to amyloid plaques and neurofibrillary tangles, cerebrovascular disease is another important pathophysiological cause of AD. Cerebrovascular disease is highly associated with vascular risk factors (VRFs). Well‐treated VRFs might decrease the risk and progression of AD. However, findings on the impact of VRFs treatment status on cognitive decline after the diagnosis of AD established are unclear, and there is no direct evidence supporting well‐treated VRFs can slow down the AD progression.MethodThis study recruited mild cognitive impairment (MCI) and mild AD patients (CDR = 0.5 or 1) with at least one VRF from at Taichung Veteran General Hospital. The treatment status of the VRFs was identified and all participants were evaluated by a standard neuropsychological test battery. We collected the participants’ brain MRI done within one year and performed Apolipoprotein E genotyping. FreeSurfer was used for structural MRI reconstruction and calculated total gray matter volume, hippocampus volume, and AD signature cortical thickness. Cerebrovascular lesions, including perivascular spaces in centrum semiovale, basal ganglia and presence of lobar cerebral microbleeds (LCMBs), and the volume of white matter hyperintensities were estimated by visual rating scales and Lesion Segmentation Tool for Statistical Parametric Mapping. We analyzed the relationships among the treatment status of VRFs, neuropsychological tests, and brain MRI.ResultWe recruited 61 patients in this study. Four patients refused to keep involving the study, 6 patients were not compatible with the criteria of MCI and AD after neuropsychiatric testing, and 4 patients’ brain MRI images cannot be analyzed after quality checked. The remaining 47 patients (15 MCI patients and 32 AD patients) constituted the final sample for analysis. The patients with well‐controlled VRFs present with similar cognitive function compared to the patients with partially‐controlled VRFs even though the more severe hippocampal atrophy was noted in the patients with well controlled VRFs. The severity of white matter hyperintensities and other cerebrovascular lesions are not correlated with the cognitive function in MCI and AD patients.ConclusionBrain reserve in the AD and MCI patients with well‐controlled VRFs might contribute cognitive function

Association between 10‐year cardiovascular mortality‐risk and neuroimaging biomarkers in the FINGER trial

AbstractBackgroundCardiovascular risk factors are associated with cognitive decline and dementia. Timely estimation and targeting of cardiovascular risk burden may contribute towards the prevention of cognitive decline. The cardiovascular risk scores of the European Society of Cardiology’s, SCORE (for adults up to 64 years) and SCORE‐OP (for older adults aged 65 years or more), are commonly used tool for estimation of 10‐year CVD mortality and may reflect the impact of cardiovascular risk burden on brain pathology if validated against neuroimaging biomarkers.MethodThis study investigated associations between (i) baseline SCORE/SCORE‐OP and baseline neuroimaging biomarkers (brain magnetic resonance imaging [MRI] and Pittsburgh Compound B‐positron emission tomography [PiB‐PET] measures) (ii) change in SCORE/SCORE‐OP and change in neuroimaging measures during the 2‐year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). FINGER targeted at‐risk older adults, aged 60‐77 years, from the general population. Participants were randomized to either multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice). Neuroimaging (MRI and PiB‐PET) data from baseline and 2‐year visits were used. A total of 112 participants had repeated brain MRI measures (hippocampus, total grey matter, and white matter lesion volumes, and Alzheimer’s disease signature cortical thickness). Repeated PiB‐PET scans were available for 39 participants.ResultPreliminary results suggest that at baseline higher SCORE/SCORE‐OP, indicating increased risk of CVD mortality was significantly associated with lower hippocampus volume (estimate = ‐0.010; p = 0.004), lower total grey matter volume (estimate = ‐0.016; p = 0.007), higher white matter lesion volume (estimate = 0.048; p = 0.015), and lower AD signature cortical thickness (‐0.004; p = 0.048) but not with PiB‐PET. No significant associations were found for change in neuroimaging measures and baseline SCORE/SCORE‐OP or change in SCORE/SCORE‐OP during the 2‐year follow‐up.ConclusionCardiovascular risk scores need to be validated against different brain pathology markers in diverse populations. This will enable more precise identification and estimation of dementia risk profiles, guiding at‐risk persons to precise intervention strategies, good for both, heart, and brain.

Pathophysiology of multiple sclerosis damage and repair: Linking cerebral hypoperfusion to the development of irreversible tissue loss in multiple sclerosis using magnetic resonance imaging.

Reduced cerebral perfusion has been observed in multiple sclerosis (MS) and may contribute to tissue loss both acutely and chronically. Here, we test the hypothesis that hypoperfusion occurs in MS and relates to the presence of irreversible tissue damage. In 91 patients with relapsing MS and 26 healthy controls (HC), gray matter (GM) cerebral blood flow (CBF) was assessed using pulsed arterial spin labeling. GM volume, T1 hypointense and T2 hyperintense lesion volumes (T1LV and T2LV, respectively), and the proportion of T2-hyperintense lesion volume that appears hypointense on T1-weighted magnetic resonance imaging (T1LV/T2LV) were quantified. GM CBF and GM volume were evaluated globally, as well as regionally, using an atlas-based approach. Global GM CBF was lower in patients (56.9 ± 12.3 mL/100 g/min) than in HC (67.7 ± 10.0 mL/100 g/min; p < 0.001), a difference that was widespread across brain regions. Although total GM volume was comparable between groups, significant reductions were observed in a subset of subcortical structures. GM CBF negatively correlated with T1LV (r = -0.43, p = 0.0002) and T1LV/T2LV (r = -0.37, p = 0.0004), but not with T2LV. GM hypoperfusion occurs in MS and is associated with irreversible white matter damage, thus suggesting that cerebral hypoperfusion may actively contribute and possibly precede neurodegeneration by hampering tissue repair abilities in MS.

Association of Arterial Stiffness and Atherosclerotic Burden With Brain Structural Changes Among Japanese Men.

Background Little is known regarding whether arterial stiffness and atherosclerotic burden are each independently associated with brain structural changes. Simultaneous assessments of both arterial stiffness and atherosclerotic burden in associations with brain could provide insights into the mechanisms of brain structural changes. Methods and Results Using data from the SESSA (Shiga Epidemiological Study of Subclinical Atherosclerosis), we analyzed data among 686 Japanese men (mean [SD] age, 67.9 [8.4] years; range, 46-83 years) free from history of stroke and myocardial infarction. Brachial-ankle pulse wave velocity and coronary artery calcification on computed tomography scans were measured between March 2010 and August 2014. Brain volumes (total brain volume, gray matter, Alzheimer disease signature and prefrontal) and brain vascular damage (white matter hyperintensities) were quantified using brain magnetic resonance imaging from January 2012 through February 2015. In multivariable adjustment models including mean arterial pressure, when brachial-ankle pulse wave velocity and coronary artery calcification were entered into the same models, the β (95% CI) for Alzheimer disease signature volume for each 1-SD increase in brachial-ankle pulse wave velocity was -0.33 (-0.64 to -0.02), and the unstandardized β (95% CI) for white matter hyperintensities for each 1-unit increase in coronary artery calcification was 0.68 (0.05-1.32). Brachial-ankle pulse wave velocity and coronary artery calcification were not statistically significantly associated with total brain and gray matter volumes. Conclusions Among Japanese men, higher arterial stiffness was associated with lower Alzheimer disease signature volumes, whereas higher atherosclerotic burden was associated with brain vascular damage. Arterial stiffness and atherosclerotic burden may be independently associated with brain structural changes via different pathways.