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Summary

Recently, I came across an interesting paper from 2013 in Lancet Neurology that adds important genetic information about the case of Auguste D, the first patient diagnosed with what was later called Alzheimer’s disease. She first came under the care of Dr. Alois Alzheimer at age 51 because of rapidly progressive memory loss, hallucinations, seizures, focal neurological signs including trouble speaking, and delusions that her husband was having an affair with the next-door neighbor, fears that were apparently unfounded. She died five years later, and Dr. Alzheimer was able to examine her brain under a microscope. He was surprised to find dark blobs outside of nerve cells and smaller dark tangles within the axons of nerve cells. He reported his findings in 1906 at the 37th Conference of South-West German Psychiatrists in Tübingen, but there was little interest from the audience. Soon other pathologists started seeing these dark extracellular blobs and intraneuronal twists in the brains of demented patients, later identified as beta-amyloid plaques and tau-containing neurofibrillary tangles. Dementia associated with these characteristic pathological findings came to be called Alzheimer’s disease in his honor.

Objective:

Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer’s disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and sex differences in the relationship between SCD and memory performance.

Methods:

We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education.

Results:

Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory.

Conclusions:

Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.

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4 - The First Patient with Alzheimer’s Disease

Summary

Subjective Cognitive Decline and its Relation to Verbal Memory and Sex in Cognitively Unimpaired Individuals from a Colombian Cohort with Autosomal-Dominant Alzheimer’s Disease

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2 results

4 - The First Patient with Alzheimer’s Disease

Summary

Subjective Cognitive Decline and its Relation to Verbal Memory and Sex in Cognitively Unimpaired Individuals from a Colombian Cohort with Autosomal-Dominant Alzheimer’s Disease