Cognitive Profiles in Amyloid-Positive Mild Cognitive Impairment and Alzheimer’s Disease with and without Tau (P2.1-030)

Objective: To determine differences in cognitive profiles of amyloid-positive individuals (A+) with mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) with and without concomitant pathologic tau (T+/T−). Background: A major source of heterogeneity in AD is mixed pathology (e.g. vascular with AD pathology), posing challenges for research and clinical care. The recently developed ATN framework for AD pathology classifies individuals based on amyloid (A), tau (T), and neurodegeneration (N) status. Tau pathology is directly linked to neurodegeneration and cognitive decline in AD. Thus, cognitive impairment in setting of amyloid without tau suggests an alternate driver of neuronal injury. Design/Methods: Data from ADNI was utilized. Inclusion criteria were amyloid positivity (based on composite SUVR of 1.11 with florbetapir PET) and diagnosis of MCI or AD. A tau cut-off of 1.22 SUVR in bilateral extrahippocampal medial temporal lobe using the novel tau PET tracer AV-1451 was derived from amyloid-negative controls. A+T− and A+T+ groups were compared. Results: 43 amyloid-positive individuals with MCI or AD met inclusion criteria: 13 A+T− and 30 A+T+. The A+T− group was older (75.8 vs 69.9 years, p=0.026), had higher MMSE (27.2 vs. 24.2, p=0.044), and better scores on verbal memory recall (AVTOT6 5.31 vs 2.70, p=0.024). However, the A+T− group performed worse on Trails B, a measure of executive function/sequencing, but this did not reach significance (145.5 vs 131.1, p=0.628). Conclusions: Amongst a cohort of amyloid-positive MCI and AD, tau-negative individuals displayed clinical differences from counterparts with concomitant tau pathology, including somewhat better memory, but, if anything, relatively more affected executive function. The less AD-like pattern of the A+T− group may support the notion that symptomatic patients who are A+T− may have non-AD pathologies driving their clinical symptoms. Further investigation will examine the burden of white matter hyperintensities, a marker of vascular disease, and patterns of cortical thickness in these groups. Disclosure: Dr. McCollum has nothing to disclose. Dr. Wisse has nothing to disclose. Dr. Das has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Rancho Biosciences. Dr. de Flores has nothing to disclose. Dr. Yushkevich has nothing to disclose. Dr. Wolk has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck, Jannsen, Eli Lilly and GE.