Heggeli · Alzheimer disease and associated disorders 2012 · matched case-control study · n=396

Maternal transmission of Alzheimer disease.

Level 4 - case-series / case-control

Matched case-control study

PubMed 22273801 · doi:10.1097/WAD.0b013e318247d203 · record verified 2026-08-26

What was done

Researchers conducted an age- and sex-matched case-control study comparing 196 Alzheimer disease (AD) cases and 200 cognitively normal controls. They collected parent dementia status and age of death for 348 parents of AD cases and 319 parents of controls, evaluating dementia frequency in mothers versus fathers and adjusting for parent age at death and APOE status.

What was found

Memory difficulty was reported in 24 (12%) control fathers, 26 (13%) AD fathers, 58 (29%) control mothers, and 55 (28%) AD mothers. Mothers were significantly more likely to have memory problems than fathers after adjusting for age at death and APOE among controls (OR = 2.40, P = 0.004), but the difference did not reach significance in cases (OR = 1.63, P = 0.14). There was no significant interaction between cases and controls (P = 0.41), and cases' mothers had no higher rate of dementia than controls' mothers (28% vs 29%).

Why it matters

The findings challenge the hypothesis of maternal inheritance in Alzheimer disease, suggesting that the higher prevalence of affected mothers compared to fathers is largely driven by female longevity.

Limits

Parental dementia status was assessed via reported family history rather than direct clinical evaluation, introducing potential recall or misclassification bias. Complete parental data were available for only 667 of an expected 792 parents.

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