ABSTRACT BACKGROUND AND PURPOSE A substantial overlap exists between declines in cerebral vasoreactivity (CVR) and symptomatic Alzheimer's disease (AD). CVR can be quantified using transcranial Doppler (TCD) measurement of cerebral blood flow velocities (CBFV) in the middle cerebral artery (MCA) with CO 2 as a vasodilatory stimulus. The breath‐hold acceleration index (BHAI) is a new, more reliable measure of CVR developed recently in our laboratory. Our primary goal is to explore the possibility of using TCD for asymptomatic AD screening. METHODS A pilot study population was divided into three groups: 9 healthy control subjects, 8 subjects identified as preclinical AD, and 10 patients diagnosed with prodromal or mild AD. Control subjects had a Clinical Dementia Rating (CDR) score of 0 without elevated amyloid‐β (Aβ) on amyloid positron emission tomography (PET) imaging, preclinical AD subjects had CDR = 0 with elevated Aβ, and prodromal to mild AD subjects had CDR scores ≥.5 and elevated Aβ. CVR was calculated using two indices: the conventional breath‐holding index (BHI) and the new BHAI. TCD parameters between the three groups were compared. RESULTS BHAI was able to distinguish between 9 normal control subjects and 8 preclinical‐AD subjects with high statistical significance ( P < .001). BHI and pulsatility index were able only to distinguish AD from healthy and preclinical subjects ( P < .001). CONCLUSIONS In this exploratory pilot study, CVR was significantly decreased in preclinical, prodromal, and mild AD subjects as compared to the healthy group. Lower CVR in the preclinical AD group was detected using the new BHAI index but not the conventional BHI index.