Cerebral Blood Flow in Alzheimer's Disease: A Meta-Analysis on Transcranial Doppler Investigations

Cerebrovascular hemodynamic impairment has been reported in Alzheimer's disease (AD). We performed a systematic review and meta-analysis to investigate changes in cerebral blood flow (CBF) in AD patients. Data were obtained by searching MEDLINE and Scopus for all investigations published between 1 January 2011 and 1 November 2021, comparing the cerebrovascular hemodynamic between AD patients and cognately healthy age-matched controls, using transcranial Doppler (TCD) ultrasound. Twelve studies, based on 685 patients [395 with AD and 290 age-matched cognitively healthy controls, with a mean age of 71.5 and 72.1 years, respectively] were included in the analysis. A random effect model revealed that AD patients, in the proximal segments of the middle cerebral artery (MCA), have a significantly lower CBF velocity, compared to controls (MD: -7.80 cm/s, 95%CI: -10.78 to -5.13, < 0.0001, I = 71.0%). Due to a significant Egger's test (t = 3.12, = 0.008), a trim-and-fill analysis was performed, confirming the difference (MD: -11.05 cm/s, 95%CI: -12.28 to -9.82, < 0.0001). Meta-regression analysis demonstrated that the mean CBF at the proximal MCA was directly correlated with arterial hypertension ( = 0.03) and MMSE score ( < 0.001), but inversely correlated with age ( = 0.01). In AD patients, the pulsatility index was significantly higher compared to controls (MD: 0.16, 95%CI: 0.07 to 0.25, < 0.0001, I : 84.5%), while the breath-holding index test results were significant lower (MD: -1.72, 95%CI: -2.53 to -0.91, < 0.001, I : 85.4%). AD patients have a significant impairment in relation to their cerebrovascular perfusion, suggesting that cerebrovascular hemodynamic deterioration, evaluated using TCD, may be a useful diagnostic tool.