1. Boston Naming Test predicts deterioration of cerebrospinal fluid biomarkers in pre-symptomatic Alzheimer’s disease Charleen Wilder, MA, Kristina Moncrieffe, MA, Anne Nolty, PhD, ABPP-CN, Michael G. Harrington, MB., ChB, FRCP
Background
Results
Results (continued)
Identifying early predictors of Alzheimer’s disease is crucial in order to provide early treatment and minimize the negative impact of the disease. The current study is a longitudinal neuropsychological examination of cognitively healthy pre-symptomatic elderly participants with cerebrospinal fluid (CSF) amyloid and tau measurements. CSF amyloid and tau levels are established biomarkers of Alzheimer’s disease.
Based on their amyloid and tau measurements, participants were classified as having normal amyloid/tau levels (NAT) or pathological amyloid/tau levels (PAT). Examining the neuropsychological differences between cognitively healthy individuals with initial normal biochemistry, NATs, and those who convert over time to abnormal biochemistry, PATs, can identify predictive behavioral markers.
Hypothesis: Neuropsychological data will predict the change in biochemistry in participants who convert from NATs to PATs over 40 months.
Figure 3. The difference in mean (SD) BNT scores are significantly stronger for the NAT-NAT participants than for the NAT-PAT participants.
Conclusion
Method
The neuropsychological data suggest that CH individuals who convert to abnormal CSF biochemistry over the course of 4 years perform worse at Time 1 on the BNT than cognitively healthy individuals who maintain normal biochemistry. We propose that performance on the BNT may predict changes in amyloid and tau biochemistry in cognitively healthy individuals.
Further work and research will focus on:
Assessing neuropsychological and clinical categories among different groups of participants
Examining the difference in BNT scores between NAT-NAT and NAT-PAT participants over time
Different age groups
Participants: A total of 63 elderly participants were classified by clinical consensus as cognitively healthy. They were tested at two time points: first at an average age of 80 years, then again 40 months later. Out of the 23 NATs, 14 remained NATs (NAT-NAT) and 9 converted to PATs (NAT-PAT) at the second time point. A logistic regression was used to classify participants based on their amyloid and tau measurements.
Biochemical classification: At the first visit, lumbar CSF was collected and assayed for Aß42 and tau using a sandwich enzyme-linked immunosorbent assay kit (Innotest β-amyloid(1-42) and Innotest hTAU-Ag, Innogenetics, Gent, Belgium) according to the manufacturer’s protocol. Multinomial logistic regression was used to determine a cutoff for the ratio Aß42/Tau that would provide 85% sensitivity in discriminating cognitively healthy individuals from those with Alzheimer’s disease or mild cognitive impairment. Cognitively healthy participants with a ratio above or on the cutoff (i.e., those with Normal Aß42/Tau proteins) were classified NAT, and those with a ratio below the cutoff (i.e., those with Pathological Aß42/Tau proteins) were classified PAT. We considered our cognitively healthy PAT participants to have pre-symptomatic Alzheimer’s disease.
Neuropsychological Testing: Participants were administered a 4-hour battery of neuropsychological tests, which included the Boston Naming Test (BNT), a measure of word retrieval based on visual cues.
Analyses: GraphPad Prism 7 was used to analyze the data. Mann-Whitney t tests were used to compare the two participant groups and determine significant differences.
4 years. Predict conversion of CSF AMT from normal to pathological. Chnats that are at greater chance of converting over 4 years.
Figure 1. The graph above shows the regression-derived cutoff for the ratio of beta-amyloid and tau that correctly classified 85% of AD patients. The plots include all participants who participated at time 1 and 2. The graph plots tau (X axis) vs. amyloid (Y axis) values for cognitively healthy NAT participants.
Test
p value
Mean (NAT-PAT) SD
(NAT-PAT)
Mean (NAT-NAT)
(NAT-NAT)
BNT
0.03
0.39
0.65
0.95
0.60
Acknowledgments
We would like to thank the L.K. Whittier Foundation and Huntington Medical Research Institutes for funding.
Figure 2. The table above shows the results of the Mann Whitney t tests and the means and standard deviations for NAT-NAT and NAT-PAT on the BNT at Time 1.