Cerebrovascular reactivity deficits in cognitively unimpaired older adults: vasodilatory versus vasoconstrictive responses

Abstract

Cerebrovascular reactivity (CVR) deficits may index vulnerability to vascular brain injury and cognitive impairment, but findings on age-related changes in CVR have been mixed, and no studies to date have directly compared age-related changes in CVR to hypercapnia versus hypocapnia. The present study compared CVR in 31 cognitively unimpaired older adults (ages 55-87) and 30 healthy younger adults (ages 18-28). Breath control tasks induced CVR to hypocapnia (0.1 Hz paced breathing) and hypercapnia (15s breath holds) during pseudo-continuous arterial spin labeling MRI. Relative to younger adults, cognitively unimpaired older adults displayed lower levels of global CVR under both hypocapnia and hypercapnia. In region-of-interest analyses, older adults exhibited attenuated CVR to hypocapnia in select frontal and temporal regions, and lower CVR to hypercapnia in all cortical, limbic, and subcortical regions examined, relative to younger adults. Results indicate age-related deficits in CVR are detectible even in cognitively unimpaired older adults and are disproportionately related to vasodilatory (hypercapnia) responses relative to vasoconstrictive (hypocapnia) responses. Findings may offer means for early detection of cerebrovascular dysfunction.

Keywords: Cerebral blood flow; Cerebrovascular reactivity; Cerebrovascular reserve; Hypercapnia; Hypocapnia; Older adults.

Fig. 1.

Schematic illustration of temporal synchronizations between breathing paradigms and pseudo-continuous arterial spin labeling (pCASL) MRI acquisitions. IN = breathe in, OUT = breathe out, NORMAL = breathe normally, BH = breath hold, img = perfusion image.

Fig. 2.

Representative end-tidal CO₂ (etCO₂) timeseries data across the duration of pseudo-continuous arterial spin labeling (pCASL) scans for 0.1Hz paced breathing (top) and breath hold (bottom) conditions. Raw capnography recordings of etCO₂ are shown as gray traces. Extracted etCO₂ values are shown in bold colored lines. Top (blue): EtCO₂ levels are gradually decreasing during 0.1Hz paced breathing (hypocapnia). Bottom (red): Dashed lines indicate breath holds. The exhale immediately following each breath hold shows an increase in etCO₂ (hypercapnia).

Fig. 3.

Average whole-brain gray-matter cerebrovascular reactivity (CVR) maps contrasting young and older adults in 0.1Hz paced breathing (top: hypocapnia) and breath hold (bottom: hypercapnia) conditions. CVR was computed as the percent change in CBF per mmHg change in etCO₂. Warm colors indicate higher CVR values, while cold colors show lower CVR values. It is easily noticeable that older adults demonstrated attenuated CVR in both conditions, compared with younger adults.