The in vivo diagnosis of Alzheimer's disease (AD) may be facilitated by 
cerebro-spinal fluid (CSF) biomarkers in combination with imaging and clinical 
assessments. By determining the concentration of beta amyloid fragments, total 
tau (t-tau) and phospho-tau (p-tau), it is possible to detect the conversion of 
mild cognitive impairment (MCI) to AD or distinguish AD vs. pseudo-dementia. 
However, these markers are poorly sensitive to the progressive disease stages. 
And far from clear is their role in "mixed" forms of dementia, as far as 
hemodynamic deficits complicate the clinical history. We have studied cerebral 
hemodynamic impairment in AD patients, relative to control subjects. Mean flow 
velocity (MFV), pulsatility index (PI) and cerebrovascular reactivity (assayed 
as breath-holding index, BHI) were evaluated by bilateral transcranial Doppler 
(TCD) monitoring of middle cerebral arteries. MFV and BHI were significantly 
lower and PI was significantly higher in AD patients with respect to control 
subjects. The presence of white-matter changes (WMC) in the AD cases did not 
influence any of the hemodynamic variables. Noticeably, MMSE score was 
correlated to BHI reduction (P<0.005). Our results, consistent with the recent 
literature indicate that hemodynamic impairment is a critical marker of 
cognitive decline and supports once more the hypothesis of a significant 
pathigenic role of vascular damage in AD. Similar functional alterations might 
be early hallmarks in a variety of dementia subtypes, including "mixed" 
dementia, whose prevalence is undoubtedly increased. Assessment of hemodynamic 
reactivity could provide valuable correlations with individual patient's 
cognitive profile, which in turn would assist in the identification of critical 
steps in disease progression and the validation of effective therapies.