Neurology

Lipoic acid provides no functional benefit and raises safety concerns in progressive MS

In this 24‑month, phase 2 randomized trial, 118 patients with primary or secondary progressive MS received lipoic acid 1,200 mg daily or placebo. Lipoic acid did not slow Timed 25‑Foot Walk decline or improve other clinical or patient‑reported outcomes versus placebo. Whole‑brain and deep gray matter volumes appeared more stable with lipoic acid despite greater T2 lesion burden, without translating into clinical benefit. The lipoic acid group had higher discontinuation rates and more proteinuria, requiring intensified laboratory monitoring. 1

Plasma p-tau217 indicates widespread Alzheimer pathology in the aging community

This Norwegian population-based study measured plasma p‑tau217 in 11,486 individuals aged 57 years or older as a surrogate for Alzheimer neuropathologic changes. Estimated Alzheimer neuropathology prevalence increased from under 8% at ages 58–69.9 to 65.2% in those older than 90 years. Among participants aged 70 or older, 10% had preclinical Alzheimer disease, 10.4% prodromal disease, and 9.8% Alzheimer dementia. In this age group, Alzheimer pathology was present in 60% with dementia, 32.6% with MCI, and 23.5% of cognitively unimpaired individuals. 2

Women experience worse functional outcomes than men during the first year after ischemic stroke

This population-based cohort included 1,046 patients with first-ever ischemic stroke followed with standardized interviews up to 12 months. Female survivors had higher ADL/IADL disability scores than males at 3, 6, and 12 months, indicating worse functional outcomes. Both sexes showed neurologic improvement, with no major sex differences in neurologic, quality-of-life, or global cognitive trajectories. Cognitive improvement over time occurred only in male survivors, suggesting subtle sex differences beyond routine scales. 3

Tau–clinical mismatch identifies vulnerable and resilient trajectories in amyloid-positive patients

This multicenter observational study analyzed amyloid‑positive participants from ADNI and Penn‑ADRC with tau PET or plasma p‑tau217 and serial Clinical Dementia Rating assessments. Using CDR‑Sum of Boxes relative to tau burden, about 55%–57% were canonical, ~24% resilient, and ~19% vulnerable. Vulnerable individuals, whose clinical impairment exceeded tau burden, showed imaging patterns suggestive of TDP‑43 involvement and higher α‑synuclein positivity. Mismatch groups had distinct longitudinal trajectories, with earlier cognitive impairment in vulnerable and delayed impairment in resilient participants. 4