In your clinical practice, how are you approaching consideration of limbic-predominant age-related TDP-43 encephalopathy (LATE) in the differential diagnosis for older adults previously thought to have Alzheimer's disease?

At the moment, I am not finding that this diagnosis is extremely helpful. In general, LATE looks for all the world like AD at the time of diagnosis in the oldest patients, but it doesn't progress like we expect it to. LATE, by itself, seems to be a much more slowly progressive disease. So I find myself looking at a patient in their mid 80's, who I diagnosed with AD a few years earlier, who is not really declining cognitively or functionally as I expected them to, and say to patients and families, "Well, maybe this is not actually AD, but a more recently recognized neurodegenerative dementia called LATE".

Until it can be diagnosed more accurately with biomarkers, and/or there are specific therapies for it, I think that's about the best that ...

I consider LATE in almost all older patients in late life (>85) when they present to me with cognitive changes.

I agree, biomarkers are necessary for a more precise diagnosis. But clinical history of slow progression and reasonably well-maintained functional status clues towards LATE rather than AD. The biggest advantage in considering this in the differential is to discuss the benign prognosis compared to AD, alleviate fears for the patient and family, and to approach amyloid imaging/MAb therapy more cautiously.