Weight Fluctuation and Dementia: 3x Increased Risk with ±10% Change (Mediated by 'APOE ɛ4' Gene)
📖 Literature Information and Abstract Translation
Association between late-life weight change and dementia: A population-based cohort study.
📕Guo, Jie, et al. "Association between late-life weight change and dementia: A population-based cohort study." The Journals of Gerontology: Series A (2022). https://doi.org/10.1093/gerona/glac157
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✅ Background Knowledge: What is 'APOE ɛ4'?
・APOEε4 is a 'genotype' said to increase the risk of developing Alzheimer's disease by approximately 3.9 times for those who carry it.・Alzheimer's dementia (Alzheimer's disease) is known to be caused by the accumulation of waste products called amyloid-beta peptides in the brain, which damage nerve cells.
・One of the substances involved in the accumulation and aggregation of amyloid-beta peptides is apolipoprotein E. The APOE gene that governs this mainly has three types: ε2, ε3, and ε4, which form a genotype in pairs.
・When examining the relationship between the presence of ε4 and the onset of Alzheimer's disease, compared to genotypes that do not carry ε4 at all,
the risk of developing Alzheimer's disease for genotypes carrying one or two ε4 alleles is said to be about 3 to 12 times higher.
[Background/Objective] The impact of late-life weight change on the onset of dementia is unclear. We aimed to investigate the association between body mass index (BMI) and weight change with dementia, and to explore the role of APOE ɛ4 in these associations.
[Methods] 1,673 non-demented participants aged 60 and older were followed for the first 6 years to detect changes in BMI/weight, and for an additional 6 years to detect the onset of dementia. BMI change ([BMIfirst 6-year follow-up - BMIbaseline]/BMIbaseline) was classified as stable (≦5%), moderate (5%-10%), or large increase/decrease (>10%). Dementia was diagnosed according to standard criteria. Data were analyzed using Cox regression models.
[Results] During the 6-year follow-up period, 102 cases of dementia were identified.
■ BMI and Dementia Risk
・Compared to a stable BMI, the hazard ratio (95% CI) for dementia was 2.61 (1.09-5.54) for a BMI increase of more than 10% and 2.93 (1.72-4.91) for a decrease of more than 10%.
■ +α: APOE ɛ4 Carrier Status and Dementia Risk
・The risk of dementia was higher in APOE ɛ4 carriers with large BMI increases (9.93 [3.49-24.6]) or decreases (6.66 [2.83-14.4]) compared to APOE ɛ4 non-carriers with a stable BMI.
[Conclusion] BMI change showed a U-shaped association with dementia risk. Large increases and decreases in weight were associated with a nearly 3-fold higher risk of dementia, which may be amplified by APOE ɛ4.
📕 Related Research: BMI and Cognition, Differences between Middle-aged and Elderly
・Subjects: 39,153 people in the US, under 65 years old
・Result ①: Higher BMI is associated with more rapid subsequent cognitive decline and increased risk of cognitive impairment in old age
・Result ②: 65 years and older: Higher BMI is associated with slower subsequent cognitive decline and decreased risk of cognitive impairment
・The inflection point is around 65 years old.
🌱 So What?: What did I find interesting?
It occurred to me that weight fluctuation is a 'final common pathway'.
・Started exercising recently → Weight optimization
・Mental stress is high recently → Overeating → Weight gain
・Started paying attention to food intake recently → Weight loss
etc...
All 'recent changes' converge into a single path called weight fluctuation.
And that weight fluctuation is linked to all kinds of health outcomes.
This study also clarified the association with one of those outcomes: 'dementia risk'.
Maintaining weight is also a pillar of the American Heart Association's recommendation, 'Life's Essential 8'.
Healthy weight: Body Mass Index (BMI) is not sufficient as a criterion for weight control or obesity assessment; it is necessary to manage visceral fat as well.
The rest is about how to manage it.
The best way is weight measurement linked to a wearable device.
At the moment, stepping on a scale, recording it, etc., is a hassle.
When this hassle is reduced to almost nothing, a significant final common pathway to health benefits will likely be opened.
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