Abstract
Normal brain aging is a multidimensional process that includes deterioration in various brain structures and functions, with large heterogeneity in patterns and rates of decline. Sex differences have been reported for various cognitive and brain parameters, but little is known in relation to neuromodulatory aspects of brain aging. We examined sex differences in dopamine D2-receptor (D2DR) availability in relation to episodic memory, but also, grey-matter volumes, white-matter lesions, and cerebral perfusion in healthy older adults (n = 181, age: 64–68 years) from the Cognition, Brain, and Aging study. Women had higher D2DR availability in midbrain and left caudate and putamen, as well as superior episodic memory performance. Controlling for left caudate D2DR availability attenuated sex differences in memory performance. In men, lower left caudate D2DR levels were associated with lower cortical perfusion and higher burden of white-matter lesions, as well as with episodic memory performance. However, sex was not a significant moderator of the reported links to D2DR levels. Our findings suggest that sex differences in multiple associations among DA receptor availability, vascular factors, and structural connectivity contribute to sex differences in episodic memory. Future longitudinal studies need to corroborate these patterns by lead-lag associations. This manuscript is part of the Special Issue entitled ‘Cognitive Neuroscience of Healthy and Pathological Aging’ edited by Drs. M. N. Rajah, S. Belleville, and R. Cabeza. This article is part of the Virtual Special Issue titled COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.
Highlights
Sex differences have been found for several brain parameters (Ritchie et al, 2018; Ruigrok et al, 2014) and researchers have highlighted the importance of understanding those for purposes of personalized medicine, susceptibility to neuropathology, and cognitive deficits in aging (Miller et al, 2015)
In previous descriptive analyses we showed a complex pattern of cognitive sex differences, with a female superiority for episodic memory, a male superiority for working memory, and no sex differences in speed of processing (Nevalainen et al, 2015)
We focus on episodic memory because it is an important cognitive ability with well-documented sex differences (Asperholm et al, 2019) that starts to show average longitudinal decline around 60 years of age (Nyberg, 2017)
Summary
Sex differences have been found for several brain parameters (Ritchie et al, 2018; Ruigrok et al, 2014) and researchers have highlighted the importance of understanding those for purposes of personalized medicine, susceptibility to neuropathology, and cognitive deficits in aging (Miller et al, 2015). Dissimilarities may stem from sex differences in gene expression (Trabzuni et al., 2013), and regulatory effects of the principal sex hormones, estrogen and testosterone (Wilson and Davies, 2007). Multimodal brain imaging studies demonstrate that normal (non-pathological) aging is a multifaceted process with large individual differences (Gorbach et al, 2017; Lindenberger, 2014; Lövden et al, 2018; Nyberg and Pudas, 2018). Sex differences have been found in brain morphology, function, neurochemistry, and synaptic function (Cahill, 2006; Cosgrove et al, 2007; Wilson and Davies, 2007). Mounting evidence demonstrates neurotrophic and neuroprotective effects of estrogen via a broad array of mechanisms, such as promotion
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