A recently recognized form of dementia, known as LATE, is reshaping understanding of cognitive decline in the elderly, with rising diagnoses and guidelines for doctors published this year. It is estimated to affect about one-third of people aged 85 or older and 10% of those aged 65 or older, often mistaken for Alzheimer's. Experts emphasize the need for a broader range of treatments for this condition.
Limbic-predominant age-related TDP-43 encephalopathy (LATE) is emerging as a distinct disease from Alzheimer's, though it often coexists with it. According to recent guidelines, it affects about one-third of people aged 85 or older and 10% of those aged 65 or older. "In about 1 in 5 people who come to our clinic, what was previously thought to be Alzheimer's disease actually appears to be LATE," says Greg Jicha, a neurologist at the University of Kentucky.
LATE progresses more slowly than pure Alzheimer's and mainly impacts memory, with symptoms like difficulty finding words. However, when combined with Alzheimer's, the condition worsens, leading to faster decline and severe symptoms such as psychosis and incontinence. About half of 85-year-olds with severe Alzheimer's also have LATE, according to Pete Nelson of the Sanders-Brown Center.
The recognition of LATE followed a 2018 meeting of 35 Alzheimer's researchers, resulting in a 2019 report defining it by abnormal TDP-43 protein accumulations, unlike amyloid plaques and tau tangles in Alzheimer's. Identified in 2006, TDP-43 is linked to disorders like amyotrophic lateral sclerosis.
In the case of Ray Hester, 79, initial tests suggested Alzheimer's, but detailed exams revealed LATE, without amyloid buildup. Diagnosis involves hippocampus imaging, which shrinks more in LATE, and symptom assessment.
Patients with pure LATE do not qualify for recently approved anti-amyloid drugs. A clinical trial at the University of Kentucky is testing nicorandil, an angina medication, in 64 participants with mild memory issues. The cause remains unknown, but the APOE4 gene raises risk.
Experts like David Wolk and Reisa Sperling note that mixed pathologies may explain modest results in Alzheimer's treatments, underscoring the need for LATE-specific research.
