The Human Subject Institutional Review Boards of Baylor College of Medicine, Oregon Health & Science University, the University of California at San Diego, VA Puget Sound Health Care System, and the University of Washington approved this study. All individuals provided informed consent, and underwent evaluation that consisted of medical history, physical and neurologic examinations, laboratory tests, and neuropsychological assessment. Laboratory evaluation included complete blood count (serum electrolytes, blood urea nitrogen, creatinine, glucose, vitamin B12, and thyroid stimulating hormone); all results were within normal limits. Exclusion criteria included moderate or heavy cigarette smoking (more than 10 packs/year), alcohol use other than social, and any psychotherapeutic drug use other than for treatment of AD or PD.
Controls were healthy volunteers who had normal cognitive performance on a battery of neuropsychological tests at the time of lumbar puncture as previously described. 15
All controls had at least one year of follow-up (median of 3 years) without demonstrating any symptoms or signs of neurologic disease. AD16
, and aMCI1
were diagnosed by established criteria. The diagnosis of PD-D was determined by established criteria10
and included the “one-year rule” for differentiation from Dementia with Lewy Bodies, viz
., dementia must occur one year after onset of motor parkinsonism in PD-D. The diagnosis of PD-CIND was made in subjects with a diagnosis of PD and a clinical dementia rating of 0.518
but without dementia as determined by PD-D criteria.
All CSF was obtained by lumbar puncture in the morning, was free of visual contamination by blood, had hemoglobin levels < 6.0 μg/ml, and was flash frozen and then stored at −80°C in polypropylene cryovials until used.19
All CSF samples from individuals in research cohorts at our institutions that met the above criteria were assayed for T-tau, P181-tau, and Aβ42
concentrations using AlzBio3 Luminex kits from Innogenetics (Alpharetta, GA) by following exactly the manufacturer’s instructions and were within the range of values reported by others.4, 7
Coded samples were analyzed by individuals who did not know any corresponding clinical information. Statistical analyses were performed with GraphPad Prism (San Diego, CA).