The Effects of Cerebrovascular Reactivity on the Coupling Between CSF Dynamics and Global Neurovascular Fluctuations in the Alzheimer's Disease Continuum.

BACKGROUND

Mounting evidence revealed that the weakened coupling between CSF flow and global brain activity (gBOLD-CSF coupling) is associated with Alzheimer's Disease (AD) pathology and cognitive impairments. However, the mechanisms underlying this weakened coupling remain unclear.

PURPOSE: To investigate the region-specific effects of cerebrovascular reactivity (CVR) on the gBOLD-CSF coupling.

STUDY TYPE: Retrospective.

POPULATION: One hundred ninety-eight cognitively normal controls (70.2 ± 8.7 years; 128 female, 70 male), 115 mild cognitive impairment patients (73.1 ± 7.1 years; 50 female, 65 male), and 24 dementia patients (75 ± 9.3 years; 14 female, 10 male) from ADNI.

FIELD STRENGTH/SEQUENCE: 3 T gradient-echo blood-oxygenation-level-dependent (BOLD).

ASSESSMENT: gBOLD-CSF coupling and CVR maps were respectively derived from resting-state fMRI. The former reflects the temporal coordination between CSF dynamics and global neurovascular fluctuations, while the latter quantifies the capacity of vessels to dilate or constrict. AD-related clinical scales including Aβ-PET, tau-PET, and cognitive assessments were also involved.

STATISTICAL TESTS: Linear regression models were employed to examine the association of gBOLD-CSF coupling with AD-related clinical scales and with CVR of major cerebral arteries. Mediation analyses were employed to investigate the potential pathways linking these metrics. p < 0.05 was considered significant.

RESULTS

gBOLD-CSF coupling was significantly associated with cognitive assessments (CDR Global: β = 0.366; ADAS-Cog: β = 10.613), accumulation of cortical summary Aβ (β = 37.937) and tau in Braak stage ROIs (Braak I-II: β = 0.444; Braak III-IV: β = 0.565; Braak V-VI: β = 0.474). Analysis also revealed the regional differences in the association of gBOLD-CSF coupling with CVR. CVR, especially in posterior cerebral arteries (PCA) region, was significantly associated with gBOLD-CSF coupling (β = -0.313). The gBOLD-CSF coupling, both directly and through its effect on the accumulation of Aβ and tau, mediated the association between CVR and cognition.

DATA

CONCLUSION

Data revealed a significant CVR-coupling association in the PCA region and potential pathways linking CVR, gBOLD-CSF coupling, AD pathology, and cognition, providing deeper insights into weakened gBOLD-CSF coupling in AD.

EVIDENCE LEVEL: 3.

TECHNICAL EFFICACY: Stage 2.