Snapshot · Parenting Hell with Rob Beckett and Josh Widdicombe
Rob's wife Lou left a Velux skylight blind open so natural light would wake her, resulting in Rob being roused at 4:30 AM during summer when it was already fully light.
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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