Objective: To evaluate the Alzheimer’s disease (AD) A/T/N biomarker classification scheme as a predictor of longitudinal cognitive outcomes in Parkinson’s disease (PD).

Background: Dementia is one of the most devastating complications of PD, affecting up to 80% of people with the disease. Co-occurring AD pathology is common in PD, and is more severe in patient with co-morbid dementia. In vivo biomarker studies of AD pathology in can be informative in PD, and the NIA-AA A/T/N biomarker classification scheme for Alzheimer’s disease is an unbiased multi-domain binary classification scheme incorporating amyloid (A), tau (T), and neuronal degeneration (N). Here we evaluate the A/T/N biomarker classification scheme as a predictor of cognitive decline in PD.

Method: 171 non-demented participants with a clinical diagnosis of PD were followed for up to 10.43 years (Med 4.11/IQR 3.23 – 8.14). Cerebrospinal fluid (CSF) was collected at enrollment, and levels of amyloid-Beta_1-42 (A), tau phosphorylated at residue Ser189 (T), and total tau (N) were measured using Innogenetics reagent on the xMAP Luminex platform. A positive or negative baseline A, T, and N score was assigned based on established cut-off values for risk of AD. The Mattis Dementia Rating Scale-2 (DRS-2) scale was administered at annual or biennial intervals, and a cognitive diagnosis (normal cognition, mild cognitive impairment, or dementia) was assigned by a consensus panel. Linear mixed effects-models were used to evaluate associations between A, T, or N status and rate of change in DRS over time.  A Cox proportional hazard model was used to evaluate the effect of A, T, or N status on time to dementia.

Results: Positive A status was associated with a lower baseline DRS-2 score, a faster rate of decline in DRS-2 score, as well as a shorter time to cognitive impairment. The T or N status did not associate with changes in DRS-2 score or time to cognitive impairment or dementia in this cohort.

Conclusion: These results demonstrate that positive amyloid status, but not tau, predicts future dementia in PD. Early changes in amyloid deposition in PD patients may be an important driver of dementia in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-a-in-the-a-t-n-alzheimers-disease-biomarker-classification-predicts-cognitive-outcomes-in-parkinsons-disease/