The relationship of parental longevity with the aging brain—results from UK Biobank

Abstract

A few studies report that parental longevity is associated with preserved cognition and physical function and lower risk of Alzheimer's disease. However, data on structural neuroimaging correlates of parental longevity and its spatial distribution are limited. This study aims to examine relationships of parental longevity with regional brain structure and to explore sex differences. We identified 12,970 UK Biobank participants (mean age=64.4, 51.5%women) with data on parental longevity, regional gray matter volumes, and white matter microstructure. Participants were categorized based on whether at least one parent lived to age 85 or older or neither parent survived to age 85. Associations of parental longevity, maternal and paternal longevity with each neuroimaging marker of interest were examined using linear regression, adjusted for demographics, APOE e4 status, lifestyle, and cardiometabolic conditions.Compared to participants whose both parents died before 85 (43%), those with at least one parent surviving to 85 (57%) had greater volumes in hippocampus, parahippocampal gyrus, middle temporal lobe, and primary sensorimotor cortex, and had lower mean diffusivity in posterior thalamic radiation and uncinate fasciculus. Associations were prominent with maternal longevity. Adjustment for cardiometabolic conditions did not affect observed associations except mean diffusivity in posterior thalamic radiation. There were no structural differences in other areas. Parental longevity is associated with preserved brain structure localized in primary sensorimotor cortex and temporal areas including hippocampus. These relationships are prominent with maternal longevity. Longitudinal studies are needed to determine whether changes in these brain structures account for the association between parental longevity and dementia.

Parental lifespan and polygenic risk score of longevity are associated with white matter hyperintensities

“…Our finding of a lack of association of the longevity measures with cortical and grey matter volumes is also consistent with the aforementioned study that examined the association with parental longevity (⩾85 yrs) (Murabito et al, 2014). However, in another study also using UK Biobank data (Tian et al, 2020), parental longevity was associated with some brain structures, including hippocampal volumes, which we did not find in the present study. The Tian et al study again defined parental longevity differently using age 85 as the cut-off, unlike our examination in relation to parental lifespan beyond 40 years, which we analysed as a continuous trait.…”

“…Observational studies have shown that individuals with long-lived parents have less cognitive impairment (Andersen et al, 2019; Dutta et al, 2014), lower risk of Alzheimer’s disease (Lipton et al, 2010), healthier brain ageing processes (Murabito et al, 2014), and better-preserved brain structure (Tian et al, 2020). Furthermore, it has been shown that age-related brain changes occur over the adult lifespan, with GM and white matter (WM) atrophy (Driscoll et al, 2009; Fjell et al, 2009; Pfefferbaum et al, 2013; Raz et al, 2010; Storsve et al, 2014) and the accumulation of WMH (Wen and Sachdev, 2004; Wen et al, 2009), which are also features of neurodegeneration and cerebrovascular burden.…”

“…Therefore, the empirical evidence indicates that GM and WMH volumes are well-established brain neuroimaging metrics associated with brain ageing. Although the relationship between parental longevity and the ageing brain has been explored (Tian et al, 2020), the associations between these ageing-related metrics and longevity-related genes, and the age and sex differences in these associations remain unclear.…”

Effect of Familial Longevity on Frailty and Sarcopenia: A Case–Control Study

“…Pain is a complex experience that involves sensory-discriminative, affective-motivational, and cognitive-evaluative dimensions. When investigating the relationships of parental longevity with the regional brain structure, some differences in zones involved in transferring and processing sensory and nociceptive information, which might support our results, have been found, but more research is needed on this issue [ 53 ].…”

Associations of Midlife Diet Quality with Incident Dementia and Brain Structure: Findings from the UK Biobank Study

“…In total, 19 IDPs were involved, including volume of grey matter (GM), the volume of white matter (WM), volume of brain (GM+WM), regional grey matter volumes (i.e., volumes of GM in superior frontal gyrus, inferior frontal gyrus, middle frontal gyrus, supplementary motor cortex, precentral gyrus, postcentral gyrus, precuneus, superior parietal lobe, parahippocampal gyrus, middle temporal gyrus, and inferior temporal gyrus), and volumes of several subcortical areas (including hippocampus, putamen, thalamus, caudate, and amygdala). Especially, volumes of grey matter, white matter, and the total brain were normalized by head size 32 . For the other IDPs, the sum of volumes in the left and right hemispheres was calculated.…”