Reduced Cerebrovascular Reserve Capacity as a Biomarker of Microangiopathy in Alzheimer's Disease and Mild Cognitive Impairment

Background: Cerebral microangiopathy in Alzheimer's disease (AD) causes chronic hypoperfusion and probably accelerates neurodegenerative changes. Objective: We hypothesize microvascular impairment could be present already in mild cognitive impairment (MCI) and can be revealed using transcranial color-coded sonography (TCCS) and the breath-holding maneuver. Methods: Three groups of subjects (AD in the stage of dementia, MCI, and cognitively normal controls) with detailed neuropsychological testing and low cerebrovascular burden (no history of stroke, no intra- or extracranial artery stenoses, and no severe vascular lesions on brain MRI), underwent a TCCS assessment of peak systolic (PSV), mean flow (MFV), and end diastolic velocities (EDV) and resistance and pulsatility indices (RI, PI) in large intracranial vessels bilaterally. Cerebrovascular reserve capacity was assessed using the breath-holding index (BHI) in middle cerebral artery (MCA) bilaterally. The ultrasound parameters were compared between the groups, correlated with neuropsychological tests, and compared between amnestic and non-amnestic MCI subtypes. Results: Fourteen AD (3 males, 67.9 +/- 11.1 years, MMSE 18.0 +/- 4.6), 24 MCI (13 males, 71.9 +/- 7.3 years, MMSE 28.0 +/- 1.6), and 24 risk factor-matched controls (14 males, 67.8 +/- 6.4 years, MMSE 29.1 +/- 1.2) were enrolled. Significant differences were found between AD and controls in MFV, EDV, RI, PI in right MCA after breath holding, in PSV, MFV, EDV in left MCA after breath holding, and in BHI on the left side. The left BHI correlated positively with verbal memory test. Conclusion: Results show decreased cerebrovascular reserve capacity in AD as a sign of impaired cerebral hemodynamic status without severe underlying atherosclerosis. This can be identified using TCCS and BHI.