Background The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer’s disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer’s Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods The program is open for laboratories using commercially available kits for Aβ, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results Forty laboratories participated. Twenty-six used INNOTESTenzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Aβ-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN-42, AβN-40, and AβN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.

We examined if baseline level of cognitive reserve (CR) and of Alzheimer’s disease (AD) biomarkers modify the rate of change in cognition among individuals with normal cognition at baseline (n=303, mean baseline age = 57 years, mean follow-up = 12 years); 66 participants subsequently developed Mild Cognitive Impairment (MCI) or dementia due to AD. CR was indexed by years of education, reading, and vocabulary measures. AD biomarkers were measured with a composite score composed of measures of amyloid, phosphorylated tau and neurodegeneration. Higher CR scores were associated with better cognitive performance, but did not modify the rate of change in cognition among those who remained cognitively normal, nor among those who progressed to MCI prior to symptom onset, independent of baseline biomarker levels. However, higher CR scores were associated with faster cognitive decline after symptom onset of MCI. These results suggest that the mechanism by which CR mediates the relationship between pathology and cognitive function is by delaying the onset of symptoms rather than reducing the rate of cognitive decline.

Background and Purpose-Changes in patterns of regional cerebral blood flow (rCBF) were assessed over a period of 6 years in 14 treated hypertensive participants (HTNs) and 14 age-matched healthy older participants (healthy controls [HCs]) in the Baltimore Longitudinal Study of Aging. Methods-Resting-state PET scans collected at years 1, 3, 5, and 7 were used to determine differences in longitudinal patterns of rCBF change in HTNs relative to HCs. Pulse pressure, arterial pressure, systolic/diastolic blood pressure, and hypertension duration were also correlated with patterns of rCBF change in the HTN group. Results-Relative to HCs, the HTN group shows greater rCBF decreases in prefrontal, anterior cingulate, and occipital areas over time, suggesting that these regions are more susceptible to hypertension-related dysfunction with advancing age. The HTN group also fails to show preservation of function over time in motor regions and in the temporal cortex and hippocampus as observed in HC. Although pulse pressure, mean arterial pressure, and systolic and diastolic pressure all correlate similarly with longitudinal rCBF changes, increased duration of hypertension is associated with decreased rCBF in prefrontal and anterior cingulate areas of functional vulnerability observed in the HTN group. Conclusions-These results show that hypertension significantly affects resting brain function in older individuals and suggest that duration of hypertension contributes significantly to the patterns of change over time.