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Age-Related Differences in Brain Morphology and the Modifiers in Middle-Aged and Older Adults.

ABSTRACT: Brain structural morphology differs with age. This study examined age-differences in surface-based morphometric measures of cortical thickness, volume, and surface area in a well-defined sample of 8137 generally healthy UK Biobank participants aged 45-79 years. We illustrate that the complexity of age-related brain morphological differences may be related to the laminar organization and regional evolutionary history of the cortex, and age of about 60 is a break point for increasing negative associations between age and brain morphology in Alzheimer's disease (AD)-prone areas. We also report novel relationships of age-related cortical differences with individual factors of sex, cognitive functions of fluid intelligence, reaction time and prospective memory, cigarette smoking, alcohol consumption, sleep disruption, genetic markers of apolipoprotein E, brain-derived neurotrophic factor, catechol-O-methyltransferase, and several genome-wide association study loci for AD and further reveal joint effects of cognitive functions, lifestyle behaviors, and education on age-related cortical differences. These findings provide one of the most extensive characterizations of age associations with major brain morphological measures and improve our understanding of normal structural brain aging and its potential modifiers.

SUBMITTER: Zhao L

PROVIDER: S-EPMC6931275 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Age-Related Differences in Brain Morphology and the Modifiers in Middle-Aged and Older Adults.

Zhao Lu L Matloff William W Ning Kaida K Kim Hosung H Dinov Ivo D ID Toga Arthur W AW

Cerebral cortex (New York, N.Y. : 1991) 20190901 10

Brain structural morphology differs with age. This study examined age-differences in surface-based morphometric measures of cortical thickness, volume, and surface area in a well-defined sample of 8137 generally healthy UK Biobank participants aged 45-79 years. We illustrate that the complexity of age-related brain morphological differences may be related to the laminar organization and regional evolutionary history of the cortex, and age of about 60 is a break point for increasing negative asso ...[more]

PMID: 30535294

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Project description:BackgroundThe impacts of age and sex on brain structures related to cognitive function may be important for understanding the role of aging in Alzheimer disease for both sexes. We intended to investigate the age and sex differences of cortical morphology in middle-aged and older adults and their relationships with the decline of cognitive function.MethodsIn this cross-sectional study, we examined the cortical morphology in 204 healthy middle-aged and older adult participants aged 45 to 89 years using structural magnetic resonance imaging (sMRI) data from the Dallas Lifespan Brain Study data set. Brain cortical thickness, surface complexity, and gyrification index were analyzed through a completely automated surface-based morphometric analysis using the CAT12 toolbox. Furthermore, we explored the correlation between cortical morphology differences and test scores for processing speed and working memory.ResultsThere were no significant interactions of age and sex with cortical thickness, fractal dimension, or gyrification index. Rather, we found that both males and females showed age-related decreases in cortical thickness, fractal dimension, and gyrification index. There were significant sex differences in the fractal dimension in middle-aged participants and the gyrification index in older adult participants. In addition, there were significant positive correlations between the cortical thickness of the right superior frontal gyrus and Wechsler Adult Intelligence Scale (WAIS)-III Letter-Number Sequencing test scores in males (r=0.394; P<0.001; 95% CI for r values 0.216-0.577) and females (r=0.344; P<0.001; 95% CI for r values 0.197-0.491), respectively. Furthermore, a significant relationship between the gyrification index of the right supramarginal gyrus (SupraMG) and WAIS-III Digit Symbol test scores was observed in older adult participants (r=0.375; P<0.001; 95% CI for r values 0.203-0.522).ConclusionsThe results suggest that, compared with males, females have more extensive differences in cortical morphology. The gyrification index of the right SupraMG can be used as an imaging marker of sexual cognitive differences between males and females in older adults. This study helps to further understand sex differences in the aging of the brain and cognition.

Project description:Awareness of Age-Related Change (AARC) describes to what extent people become aware of changes which they attribute to getting older. So far little is known regarding how different AARC dimensions change over time, to what extent these changes in different domains of AARC gains and losses are interrelated, and which predictors account for inter-individual differences in within-person longitudinal trajectories. Specifically, the extent to which individuals perceive age-related gains and losses might be shaped by their chronological age, their personality as well as by their general views on aging (i.e., their age stereotypes). We investigated changes in global and domain-specific AARC gains and losses over about five years in a sample of originally N = 423 participants aged 40 to 98 years at baseline. We analyzed the role of personality traits and age stereotypes for levels and changes of AARC, taking into account participants' age at baseline and controlling for gender, education, and subjective health. Based on longitudinal multilevel regression models, we observed mean-level declines in most AARC gain domains. In contrast, perceived general AARC losses, as well as AARC losses in health and physical functioning, in cognitive functioning and in social-cognitive/socio-emotional functioning remained, on average, stable over time. Baseline scores on AARC gains (global scale) were higher among individuals with higher neuroticism, openness, conscientiousness and more positive age stereotypes. Additionally, the association of higher neuroticism with higher AARC gain scores was stronger among individuals with more positive age stereotypes. Higher neuroticism and more negative age stereotypes also predicted higher baseline scores on AARC losses (global scale). At the same time, higher neuroticism was associated with a steeper decrease in AARC loss perceptions over time. Most of the intercorrelations within the intercepts and within the intra-individual trajectories of the different AARC domains were positive, but small in size. Our findings show the importance of considering trajectories of age-related gains and losses in parallel and across multiple developmental domains when investigating the subjective perception of the aging process. They also suggest that personality traits and general age stereotypes are related with individual experiences of aging.

Project description:Changes of cardiac-induced regional pulsatility can be associated with specific regions of brain volumetric changes, and these are related with cognitive alterations. Thus, mapping of cardiac pulsatility over the entire brain can be helpful to assess these relationships. A total of 108 subjects (age: 66.5 ± 8.4 years, 68 females, 52 healthy controls, 11 subjective cognitive decline, 17 impaired without complaints, 19 MCI and 9 AD) participated. The pulsatility map was obtained directly from resting-state functional MRI time-series data at 3T. Regional brain volumes were segmented from anatomical MRI. Multidomain neuropsychological battery was performed to test memory, language, attention and visuospatial construction. The Montreal Cognitive Assessment (MoCA) was also administered. The sparse partial least square (SPLS) method, which is desirable for better interpreting high-dimensional variables, was applied for the relationship between the entire brain voxels of pulsatility and 45 segmented brain volumes. A multiple holdout SPLS framework was used to optimize sparsity for assessing the pulsatility-volume relationship model and to test the reliability by fitting the models to 9 different splits of the data. We found statistically significant associations between subsets of pulsatility voxels and subsets of segmented brain volumes by rejecting the omnibus null hypothesis (any of 9 splits has p < 0.0056 (=0.05/9) with the Bonferroni correction). The pulsatility was positively associated with the lateral ventricle, choroid plexus, inferior lateral ventricle, and 3rd ventricle and negatively associated with hippocampus, ventral DC, and thalamus volumes for the first pulsatility-volume relationship. The pulsatility had an additional negative relationship with the amygdala and brain stem volumes for the second pulsatility-volume relationship. The spatial distribution of correlated pulsatility was observed in major feeding arteries to the brain regions, ventricles, and sagittal sinus. The indirect mediating pathways through the volumetric changes were statistically significant between the pulsatility and multiple cognitive measures (p < 0.01). Thus, the cerebral pulsatility, along with volumetric measurements, could be a potential marker for better understanding of pathophysiology and monitoring disease progression in age-related neurodegenerative disorders.

Project description:BackgroundAntidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users.MethodsThe association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated.ResultsIn antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26-0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17-3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07-2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05-3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01-1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decreased risk (OR = 0.96, 95% CI 0.92-1.00).ConclusionThis is the first study showing that certain genetic variants modify antidepressant-related fall risk. The results were not always consistent across the studies and should be validated in a study with a prospective design. However, pharmacogenetics might have value in antidepressant (de)prescribing in falls prevention.

Dataset Information

Age-Related Differences in Brain Morphology and the Modifiers in Middle-Aged and Older Adults.

Publications

Age-Related Differences in Brain Morphology and the Modifiers in Middle-Aged and Older Adults.

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