Abnormal Vascular Hemodynamics Linked With Tau, Constant Therapy Shows Feasibility in Alzheimer Disease, LIFT-AD Study Amended

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Welcome to this special edition of Neurology News Network. I’m Marco Meglio.

Recently published cross-sectional data from the Framingham Heart Study (FHS) showed that higher aortic stiffness and pressure pulsatility were associated with greater rhinal and entorhinal tau burden, supporting the hypothesis that abnormal central vascular hemodynamics contributes to increased tau in specific brain regions susceptible to early tau protein deposition. Published in JAMA Neurology, the study included 257 middle-aged and older adults without dementia who successfully underwent comprehensive hemodynamic evaluations and were considered on the spectrum of vascular risk. After undergoing PET scans, arterial tonometry was used to assess measures of aortic stiffness and pressure pulsatility, including carotid-femoral pulse wave velocity, central pulse pressure, and forward wave amplitude. The study also used C-Pittsburgh compound B (PiB) and FTP to assess the burden of amyloid-ß (Aß) plaques and tau protein deposition in the brain, respectively. Participants in the highest Aß quintile (≥ 1.09 PiB distribution volume ration) were classified as positive for elevated Aß burden.

Constant Therapy, an at-home mobile program geared towards improving cognitive and speech function, demonstrated safety and feasibility in a recent small-scale study of patients with mild cognitive impairment (MCI) secondary to Alzheimer disease (AD).1 Over a 24-week training period, patients adhered more to Constant Therapy than to the paper-and-pencil training, as well as improved their performance over time. In total, 8 of 10 (80%) of participants in the Constant Therapy group completed 24 weeks of the intervention, 5 of whom continued beyond the 24-week period. These participants showed an overall improvement in accuracy and latency (P = .005) in the Constant Therapy scores—scores it calculates with recorded data and session activity to summarize user performance in a specific skill domain—as well as specific improvements in tasks of visual and auditory memory, attention, and arithmetic. No unexpected problems or adverse events were observed. By design, Constant Therapy uses patented artificial intelligence technology to deliver over 244 personalized exercises that rebuild cognitive and speech function for those recovering from stroke or traumatic brain injury or living with aphasia, dementia, and other neurological conditions.

After previously showing higher potential as a monotherapy, Athira Pharma announced it was amending the ongoing pivotal LIFT-AD trial to assess its investigational agent fosgonimeton in patients with Alzheimer disease (AD) without background AChEI inhibitors. LIFT-AD, a double-blind, placebo-controlled, parallel-group study, will continue to have outcomes measured by the Global Statistical Test, which combines scores assessing cognition (Alzheimer’s Disease Assessment Scale-Cognitive Subscale [ADAS-Cog11]) and function (Alzheimer’s Disease Cooperative Study-Activities of Daily Living [ADCS-ADL23]). The study has enrolled more than 300 patients with mild-to-moderate Alzheimer disease in the US, with enrollment still ongoing. According to the update, an independent, unblinded interim analysis will be conducted to inform the required sample size needed to appropriately power the primary end point target patient population. Fosgonimeton, a small molecule HGF and MET enhancer previously known as ATH-1017, failed to meet its primary or secondary end points in the phase 2 ACT-AD study when used with standard-of-care AChEIs. Despite this, the agent did show a potentially meaningful difference change of –28 ms in event-related potential (ERP) P300 latency, the primary end point assessing working memory processing speed, after 28 weeks.

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