Cerebrovascular integrity affects gradients of aging-related dopamine D1 differences in the striatum

Extant research suggest aging-related losses of different dopaminergic markers, including presynaptic dopamine transporters as well as post-synaptic DA receptors. Given the central role of DA in neurocognitive functions, maintenance of a healthy DA system may be a key to mitigate age-related cognitive decline. Mechanisms behind DA losses in aging are however largely uncharted. Past research documented an association between dopaminergic integrity and cerebrovascular health (via white matter lesion volumes). However, it remains unclear whether proximity to lesions affected the spatial patterns of age-related D1DR differences within the striatum, and whether such differences are related to mnemonic function. Here, a large cohort of middle-aged to older healthy participants (age = 40-80 years, n = 119, 50 % women) was assessed for D1-receptor (D1DR) availability with positron emission tomography using [¹¹C]SCH23390, and for white matter lesions using FLAIR-MRI. We found evidence for variations in degree of age-related differences along the ventro-dorsal axis, with more pronounced differences in the dorsal caudate. Further analyses revealed an association between distance to lesions and extent of D1DR losses in the caudate. Furthermore, D1DR differences in dorsal caudate (proximal to lesions) was more strongly associated with memory performance. In conclusion, the present findings suggest that maintenance of cerebrovascular health may be a key factor in promoting successful dopaminergic and memory aging.