Cerebral vasomotor reactivity across the continuum of subjective cognitive impairment, amnestic mild cognitive impairment and probable Alzheimer's dementia: A transcranial Doppler and PET/MRI study

Cerebrovascular dysfunction has been suggested as a physiomarker of Alzheimer's disease (AD)-associated neuronal degeneration, but the underlying mechanisms are still debated. Herein cerebral vasomotor reactivity (VMR, breath-hold index: BHI), metabolic activity (lobar SUVs, FDG PET MRI), amyloid load (Centiloid score, Flutemetamol PET MRI), hemispheric cortical thickness, white matter lesion load and cerebral blood flow (ASL) were studied in 43 consecutive subjects (mean age: 64 years, female 13), diagnosed with subjective cognitive impairment (SCI, n = 10), amnestic mild cognitive impairment (aMCI, n = 15), and probable Alzheimer's dementia (AD, n = 18). BHI was significantly reduced in AD and aMCI patients compared to SCI subjects. A highly significant inverse correlation was found between BHI and the centiloid score (r = -0.648, p < 0.001). There was moderate positive correlation between BHI and frontal, temporal and parietal FDG SUV and ASL values, and a borderline negative correlation with age and white matter lesion volume. The link between amyloid burden and VMR was independent and strong in linear regression models where all these parameters were included (β from -0.580 to -0.476, p < 0.001). In conclusion, our study confirms the negative association of cerebral amyloid accumulation and vasomotor reactivity in Alzheimer's disease with the most direct data to date in humans.