Table 3.
Results of eligible studies included in this review pertaining to the association between ACEs and AD.
| First author (ref), country, year | Data analysis | Presented values | Quality rating | Results | Adjusted for confounders | Summary of associations |
|---|---|---|---|---|---|---|
| Norton et al. (2011), USA. | Logistic regression analyses | Odds ratio (p value) | Good−11/13 | Maternal & Paternal death - Overall: p = 0.005 0 – 4 years: 1.413 (0.243) 5 – 10 years: 0.736 (0.348) 11 – 17 years: 2.315 (0.001) Maternal death - Overall: p = 0.005 0 – 4 years: 1.452 (0.207) 5 – 10 years: 0.735 (0.346) 11 – 17 years: 2.266 (0.001) Paternal death - Overall: p = 0.073 0 – 4 years: 2.228 (0.009) 5 – 10 years: 1.145 (0.628) 11 – 17 years:1.059 (0.803) Adjusted for gender - Maternal & Paternal – 1.337 (0.005) Maternal - 1.338 (0.004) Paternal - 1.331 (0.005) Adjusted for e4 allele - Maternal & Paternal – 1 copy= 3.093 (<0.001)/2 copies = 10.558 (<0.001) Maternal – 1 copy = 1 copy= 3.083 (<0.001)/2 copies = 10.852 (<0.001) Paternal - 1 copy = 1 copy= 3.086 (<0.001)/2 copies = 10.558 (<0.001) Orphanhood – (OR = 1.59, Wald = 0.78, df = 1, p = 0.378) Parental age at participants birth - Maternal [OR = 1.02, (0.017)] / AD net [OR = 1.01, (0.403)] Paternal [OR = 1.01, (0.019)] / AD net [OR = 1.00, (.966)] Maternal death during the participants adolescence [OR = 2.27, (0.001)] Paternal death before age 5 [OR = 2.10, (0.021)] Major depressive disorder lifetime history - Maternal death during adolescence had a MDD prevalence of 30%, and subjects exposed at ages younger than 11 had a MDD prevalence of 23% (χ2 = 2.645, df = 2, p = 0.266). |
APOE, education, age, gender, SES | Both maternal and paternal death together were associated with a higher rate of AD. Maternal death was significantly associated with higher odds of AD, with the risk more than doubling with maternal death occurring during adolescence (11 – 17 years) and paternal death before age 5. Furthermore, orphanhood was not associated with a higher risk of AD. Moreover, investigation of parental death with and without remarriage of a widowed parent during the remaining years of a participant's childhood, found paternal death was no longer associated with AD. Although, maternal death during adolescence was associated with a higher risk of AD when the widowed father did not remarry. Participant gender and e4 allele was tested as a potential moderator of maternal and paternal death and AD risk. Gender or e4 allele did not moderate either association. Additionally, both maternal age and paternal age at the participants birth were associated with a higher risk of AD. However, when tested for their association with AD net of maternal and paternal death, both maternal age and paternal age at the participants birth were no longer associated with AD. However, the associations between maternal death during the participants adolescence and paternal death before age 5 with AD remained robust after adjustment for parental ages at participants' birth. Furthermore, they also investigated a lifetime history of MDD, Participants with maternal death during adolescence had a MDD prevalence of 30%, and ages younger than 11 had a MDD prevalence of 23%. However, this association did not reach statistical significance. |
| Norton et al. (2016), USA | Cox regression analysis | Wald statistic, df, and p values | Good – 11/13 | Aged 65–69 years - Wald = 5.79, df = 2, p = 0.055 Aged 70–74 years - Wald= 2.02, df = 2, p = 0.364 Aged 75–79 years - Wald= 0.63, df = 2, p = 0.729 Aged 80 years or older - Wald= 4.46, df = 2, p = 0.108 Cumulative deaths during childhood 65-69 years (Wald = 5.33, df = 2, p = 0.070) 70-74 years (Wald = 1.90, df = 2, p = 0.386) 75-79 years (Wald = 0.83, df = 2, p = 0.659) 80 years or older (Wald = 4.61, df= 2, p = 0.100) |
APOE genotype, age, gender | There was a trend for the association between parental deaths and AD risk for persons aged 65–69 years. There was no association detected among persons aged 70–74 years, 75–79 years, and 80 years or older. Additionally, cumulative deaths during childhood were explored for each age group. The number of childhood deaths was not significant among all age groups. |
| Radford et al. (2017), Australia. | Multivariate logistic regression | Odds ratio (95% CI) | Fair – 8/12 | 1.77 (CI: 1.08–2.91) | Age | Higher adverse childhood experience scores from the Childhood Trauma Questionnaire-Short Form were associated with AD. |
AD, Alzheimer's disease; df, Degrees of freedom; CI, Confidence Interval; SES, Socioeconomic status; APOE, Apolipoprotein E; MDD, Major Depressive Disorder.