title: CSF biomarkers, impairment of cerebral hemodynamics and degree of cognitive decline in Alzheimer's and mixed dementia.
abstract: 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.
authors.affiliation: Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy. stefani@uniroma2.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Stefani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sancesario
authors.forename: Mariangela
authors.initials: M
authors.lastname: Pierantozzi
authors.forename: Giorgia
authors.initials: G
authors.lastname: Leone
authors.forename: Salvatore
authors.initials: S
authors.lastname: Galati
authors.forename: Atticus H
authors.initials: AH
authors.lastname: Hainsworth
authors.forename: Marina
authors.initials: M
authors.lastname: Diomedi
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D003071:Cognition; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000503:physiopathology*; D015331:Cohort Studies; D003704:Dementia / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004453:Echoencephalography; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011569:Psychiatric Status Rating Scales; D017585:Ultrasonography, Doppler, Transcranial; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins