Snapshot · We Need To Talk with Paul C. Brunson
Briel suppressed her identity due to religious pressure and family expectations from childhood until age 23, when she came out as trans and began to live authentically.
Amyloid deposition can begin two to three decades before the onset of clinical cognitive symptoms.
About 25% of community-dwelling people in their seventies have amyloid in their brains without any symptoms of dementia.
By age 90, approximately 44% of community-dwelling people have brain amyloid without dementia symptoms, undermining blood-test specificity.
Gayatri Devi's slow-titration protocol for APOE4 carriers on anti-amyloid monoclonal antibodies yields only a 4% rate of ARIA, far below standard protocols.
Autopsy studies show that between 98% and 99% of Alzheimer's patients have some form of concomitant primary brain pathology, most commonly vascular disease.
About 40% of Alzheimer's patients eventually develop some level of Lewy body pathology, illustrating significant dementia overlap.
Anti-amyloid therapies like lecanemab and donanemab show only 0.3–0.4 point improvements on the 18-point CDR Sum of Boxes scale, a modest but potentially meaningful shift.
Approximately 30% of patients enrolled in Alzheimer's drug trials did not actually have Alzheimer's by pathology, having been misdiagnosed clinically.
Carrying two copies of the APOE4 allele increases Alzheimer's risk by approximately 60% compared to the APOE3/3 wild type, analogous to carrying the BRCA gene for breast cancer.
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