One metric that may underlie neurological changes in Long COVID among older adults is Cerebrovascular reactivity (CVR), which is an indicator of neurovascular function and has been found to correlate with cognitive decline in aging. CVR relies on vascular and inflammatory processes, making it an interesting metric, as Long COVID is a heterogeneous condition. To examine CVR in older Long COVID patients, a subject-specific abnormalities (SSA) approach called Distribution corrected z-scores (DisCo-Z) was employed, which may be more suited to detect differences. The study also examined the association between CVR and subjective cognitive concerns.

24 (6 men, 8 women) healthy older adults (mean age = 66.7 years) and 15 (6 men, 9 women) older adults with Long COVID (mean age = 66.7 years) performed a breath-holding fMRI task while in the MR scanner to examine CVR. DisCo-Z was used to examine the presence and size of extreme clusters of increased or decreased CVR (>100 voxels) within the seven Yeo functional networks. Non-parametric tests were used to examine group differences in presence and mean size of extreme clusters. Finally, relationships between the extent of subjective cognitive concerns and extreme cluster values in Long COVID were examined.

The groups did not differ significantly on age (p = 0.324) or sex (p = 0.323).  Within the Ventral Attention (p=.028) and Limbic (p=.049) networks there was a greater incidence of positive extreme clusters observed in Long COVID (with minimal incidences of negative extreme clusters across networks). Group differences were observed for mean cluster size in the Ventral Attention network (p=.016), as well. Extent of subjective cognitive concerns (range: 3-6 cognitive domains impacted) was positively correlated with DisCo-Z values for the Ventral Attention network (p=.021) with a trending level of significance for the Limbic network (p=0.053).

Using the SSA approach, abnormal CVR amongst the elderly patients with Long COVID were identified. These differences were noted within functional networks that are believed to be responsible for attention, executive function, and emotional regulation. Further, these findings were associated with a number of reported subjective cognitive concerns. Though preliminary, these findings suggest that CVR could potentially be a neurobiological mechanism linked to subjective cognitive decline in older adults with Long COVID. Future research is warranted to evaluate the relationships between CVR and the potential acceleration of cognitive decline within Long COVID in aging.