Aging-related magnification of genetic effects on cognitive and brain integrity

Influence of the DRD2/ANKK1 Taq1A polymorphism on caudate volume in older adults without dementia

“…This inconsistency may reflect the relatively small sample sizes and the heterogeneity of the investigated samples. As predicted by the resource-modulation hypothesis (Lindenberger et al 2008; Papenberg et al 2015a), the association between genes and different phenotypes may be weaker in younger adults and individuals with dementia compared with normal older adults. To address these possibilities, we explored the interaction between the DRD2/ANKK1 Taq1A polymorphism and age on caudate volume in a large sample of older adults without dementia ( n  = 387).…”

“…A recent meta-analysis of cross-sectional PET and SPECT studies found reliable negative effects of age on D1 and D2 receptors and DA transporters, but a spared DA synthesis capacity with age, which might act as a compensatory mechanism for reduced DA receptor binding (Karrer et al 2017). An increasing number of studies have found that the effects of genetic variations on cognition, brain structure, and brain function may be magnified in aging (for a review, see Papenberg et al 2015a). The resource-modulation hypothesis assumes that genetic influences on cognition are more pronounced for individuals with limited neuroanatomical or neurochemical resources, such as older adults (Lindenberger et al 2008).…”

Executive function performance and change in aging is predicted by apolipoprotein E, intensified by catechol-O-methyltransferase and brain-derived neurotrophic factor, and moderated by age and lifestyle

“…An APOE effect modification would be observed if there is, as expected, a differing relationship of ( COMT + BDNF ) on executive functioning in the context of APOE stratification (i.e., ε4+ versus ε4- groups). According to the brain-resource modulation hypothesis (Lindenberger et al, 2008; Papenberg et al, 2015a), genetic effects may be magnified in late adulthood, as compared with earlier adulthood. Therefore, our dynamic synergistic analyses involves both the overall sample ( n = 634; age range = 53–95 years) and as stratified by age group.…”

Neurocognitive functioning and genetic variation in patients with primary brain tumours

“…Explanations for this variability include gene-gene and gene-environment interactions, with some evidence suggesting that genetic effects upon neurocognition may become magnified in older adults. 14 However, when investigating genetic influences upon neurocognitive functioning in medical populations, one must also consider the possibility that stochastic events (e.g., disease and treatment) may have greater effects on neurocognition than genetic variability, obscuring inter-individual differences in relationships between genes and neurocognition. Indeed, this has been observed in patients with Alzheimer’s disease, in which heritability of neurocognitive function is less than that of their unaffected family members.…”

“…Further, smoking may attenuate some of the risk associated with the ε4 polymorphism, perhaps by counteracting cholinergic dysfunction known to be associated with the at-risk allele. 14 …”