This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a single-site, investigator-initiated study of transcranial color doppler (TCD) in the diagnosis of mild cognitive impairment (MCI). Up to forty percent of individuals with MCI convert to Alzheimer's disease per year; thus, diagnosis at the MCI stage may result in earlier intervention with medications that may promote optimal functioning and help to slow the progression of memory loss. Interventions that could achieve even modest reductions in the rate at which MCI converts to dementia would result in considerable healthcare savings. TCD provides objective measures of blood flow velocities in the basal cerebral arteries that are reliable, reproducible, and that can be followed over time. Cerebrovascular reactivity (CVR) can be assessed with TCD using acetazolamide (ACZ). A linear relation exists between a change in flow velocity and a change in cerebral blood flow (CBR) after ACZ injection, suggesting that the change in flow velocity can be used as an indicator of CVR. The hypothesis of this study is that TCD can differentiate between normal aging and MCI.
The specific aims i nclude determining the sensitivity, specificity, and positive and negative predictive values of TCD in detecting MCI. The study hopes to identify whether resting mean cerebral blood flow velocity (MCBFV) or post-ACZ CVR indices best discern MCI. Among the CVR indices, the study would like to determine whether the absolute or relative differences between resting and post-ACZ MCBFV differentiate the two groups. It is expected that there will be little or no differences in the resting MCBFV between the normal individuals and those with MCI. However, it is predicted that when individuals with MCI are stressed with ACZ, CVR indices post-ACZ will be reduced by fifty percent or more, indicating that they have reduced CVR. Ten patients with MCI and ten age-matched normal individuals will be recruited over a one-year period from the University Memory and Aging Center (UMAC) registry. If subjects have not had a neuropsychological examination in the last year they will complete standardized cognitive and neuropsychological assessments at the UMAC prior to the TCD. Resting MCBFV and pulsatility indices (PI) are obtained during the first TCD. One gram of ACZ is then injected through a vein in the subject's arm. Twenty-minutes post ACZ, another TCD is performed and the following measurements are made: MCBFV, PI, and CVR indices (i.e. absolute and relative differences in MCBFV between pre- and post-ACZ). Blood pressure and heart rate will be obtained prior to and after each TCD is performed. All subjects will have one outpatient study visit at the GCRC for a blood draw, transcranial color doppler, and an injection of acetazolamide.
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