Athanasia M. Mowinckel
Profile Url: athanasia-m--mowinckel
Researcher at University of Oslo
0
0
0
Video Abstract (AI generated)
Paper
Preprint
SI
While development and aging of the cerebral cortex show a similar topographic organization and are mainly governed by the same genes, it is unclear whether the same is true for subcortical structures, which follow fundamentally different ontogenetic and phylogenetic principles than the cerebral cortex. To test the hypothesis that genetically governed neurodevelopmental processes can be traced in subcortical structures throughout life, we analyzed a longitudinal magnetic resonance imaging dataset (n = 974, age 4-89 years), identifying five clusters of longitudinal change in development. With some exceptions, these clusters followed placement along the cranial axis in embryonic brain development, suggesting continuity in the pattern of change from prenatal stages. Developmental change patterns were conserved through the lifespan and predicted general cognitive function in an age-invariant manner. The results were replicated in longitudinal data from the Lifebrain consortium (n = 756, age 19-83 years). Genetic contributions to longitudinal brain changes were calculated from the Vietnam Era Twin Study of Aging (n = 331 male twins, age 51-60 years), revealing that distinct sets of genes tended to govern change for each developmental cluster. This finding was confirmed with single nucleotide polymorphisms and cross-sectional MRI data from the UK Biobank (n = 20,588, age 40-69), demonstrating significantly higher co-heritability among structures belonging to the same developmental clusters. Together, these results suggest that coordination of subcortical change adheres to fundamental principles of lifespan continuity, genetic organization and age-invariant relationships to cognitive function. ### Competing Interest Statement The authors have declared no competing interest.
0
0
0
Video Abstract (AI generated)
Paper
Preprint
Supplementary
Brain age is an influential index for quantifying brain health, assumed partially to reflect the rate of brain aging. We explicitly tested this assumption in two large datasets and found no association between cross-sectional brain age and steeper brain decline. Rather, brain age in adulthood was associated with early-life influences indexed by birth weight and polygenic scores. The results call for nuanced interpretations of cross-sectional indices of the aging brain.
0
0
0
Video Abstract (AI generated)
Paper
Preprint
Supplemental Information
Socio-economic status (SES) has been proposed to have facilitating and protective effects on brain and cognition. Here we show that relationships between SES, brain volumes and general cognitive ability differ significantly across European and US cohorts (4-97 years, N â 500,000; 54,000 with brain imaging). Education was positively related to intracranial (ICV) and total brain gray matter (GM) volume. Income was related to ICV, but not GM. Relationships varied significantly across samples, and SES was more strongly related to brain and cognition in US than European cohorts. Differences in neuroanatomical volumes explained part of the SES-cognition relationships. SES was more strongly related to ICV than to GM, implying that SES-cognition relations in adulthood are less likely grounded in neuroprotective effects on GM volume in aging. Rather, a relationship may be established early in life. The findings underscore that SES has no uniform association with, or impact on, brain and cognition. ### Competing Interest Statement Christian A Drevon is a cofounder, stock-owner, board member and consultant in the contract laboratory Vitas AS, performing personalized analyses of blood biomarkers. None of the other authors declare competing interests.
0
0
0
Video Abstract (AI generated)
Paper
Preprint
INTRODUCTION: It is unknown whether genetic risk for Alzheimer`s disease (AD) represents a stable influence on the brain from early in life, or whether effects are age-dependent. It is critical to characterize the effects of genetic risk factors on the primary neural substrate of AD, the hippocampus, throughout life. METHODS: Relations of polygenic risk score (PGS) for AD, including variants in Apolipoprotein E (APOE) with hippocampal volume and its change were assessed in a healthy longitudinal lifespan sample (n = 1181, 4-95 years), followed for up to 11 years with a total of 2690 MRI scans. RESULTS: AD-PGS showed a significant negative effect on hippocampal volume. Offset effects of AD-PGS and APOE ϔ4 were present in hippocampal development, and interactions between age and genetic risk on volume change were not consistently observed. DISCUSSION: Endophenotypic manifestation of polygenic risk for AD may be seen across the lifespan in healthy persons.