Clinical Diagnoses and Characterization of Patients With Amyloid-Negative Amyloid-Beta, p-Tau, and Neurofilament...

The novel amyloid-beta, p-Tau, and neurofilament light chain (ATN) classification scheme has become a promising system for clinically detecting and diagnosing Alzheimer's disease (AD). In addition to its utility in Alzheimer's diagnosis and treatment, the ATN framework may also have clinical relevance in identifying non-Alzheimer's pathologies. In this study conducted at Broadlawns Geriatric and Memory Center, 92 amyloid-negative profiles out of 182 patients with an ATN framework were categorized into subjective cognitive impairment (SCI), non-amnestic mild cognitive impairment (non-amnestic MCI), amnestic MCI, Alzheimer's dementia, vascular dementia, mixed dementia, unspecified dementia, or other memory changes based on diagnoses written in the chart. Additionally, other secondary diagnoses were found in the differential, including sleep disorders, anxiety, depressive disorders and grief, and cerebrovascular disease. The results are concordant with our expectations that amyloid-negative ATN profiles are associated with mostly non-Alzheimer's cognitive decline. We were also able to demonstrate that amyloid-negative patients have other secondary neurologic or psychiatric diagnoses related to memory or cognitive changes. However, certain enigmatic patient presentations warrant further scrutiny in the medical chart. It is possible that ATN may pose a risk of misclassification in both Alzheimer and non-Alzheimer pathologies, particularly at early stages. Future work may be required to corroborate findings using other new plasma biomarkers, such as p-Tau217. Overall, we hope that this study will provide options for early detection and future treatment of AD and other neurocognitive disorders. We also anticipate that this work will lead to the recognition of other non-neurocognitive conditions comorbid with such neurocognitive disorders.