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P1‐143: LONGITUDINAL CHANGES IN CEREBROSPINAL FLUID BIOMARKERS OF ALZHEIMER'S DISEASE: FINDINGS FROM A COGNITIVELY NORMAL, MIDDLE‐AGED COHORT
Author(s) -
Sutphen Courtney L.,
Shah Aarti R.,
Jasielec Mateusz,
Xiong Chengjie,
Vlassenko Andrei G.,
Benzinger Tammie,
Stoops Erik,
Vanderstichele Hugo,
Brix Britta,
Darby Heather,
Leen Jef Vandijck Manu,
Ladenson Jack H.,
Holtzman David,
Morris John Carl,
Fagan Anne M.
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.380
Subject(s) - medicine , biomarker , cohort , dementia , cerebrospinal fluid , clinical dementia rating , natural history study , disease , longitudinal study , oncology , clinical trial , population , cognitive decline , cohort study , pathology , biochemistry , chemistry , environmental health
possible contribution of alterations in cerebral hemodynamics to the evolution of cognitive impairment in patientswithAD.Methods:A total of 232 subjects representing 5 1 controls, 82 patients with mild cognitive impairment (MCI) and98patientswithADwere included.Demographiccharacteristics, vascular risk profile, themini-mental state examination (MMSE) and clinical dementia rating (CDR)were assessed, andmagnetic resonance imaging of the brainwas performed to evaluate the white matter hyperintensities (WMHs) of subjects. By using TCD, cerebrovascular reactivity (CVR) to hypercapnia was evaluated by the breath-holding, in addition to the mean blood flow velocity (MFV), pulsatility index (PI) and resistance index (RI) of the middle cerebral artery. Analyses were adjusted for age, education, severity of WMHs, and vascular risk factors such as the presence of cerebral artery stenosis. Results: ADpatientswere olderand low-educated, compared to controls orMCIpatients (all, p<0.001). The severity of WMHs as well as MMSE and CDR were also different, independently to age and education. After adjusting for other additional covariate, TCD parameters such asMFV, PI and RI did not differ among three groups. However, CVR was significantly reduced in AD group (45.69611.74 cm/sec), compared with other groups (56.22614.78 cm/sec in controls and 53.25615.26 cm/sec in MCI, p<0.001). CVR was correlated with MMSE score (r 1⁄40.228, p1⁄40.001). Conclusions: Our finding that CVR is reduced in AD, independent of large cerebral artery stenosis, may be suggestive of underlying microangiopathic mechanism in AD patients. Furthermore, there was an association between impaired function of cerebral microvessels and cognitive decline in subjects, including cognitively normal elders and AD.