Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia.
Level 4 - case-series / case-control
Case-control cross-sectional neuroimaging study
PubMed 14688411 · doi:10.1073/pnas.2635903100
What was done
Normal volunteers aged 20–39 years underwent apolipoprotein E (APOE) genotyping. Twelve ε4 heterozygotes (all ε3/ε4 genotype) and 15 noncarriers (12 individually matched for sex, age, and educational level) underwent clinical evaluations, neuropsychological testing, MRI, and fluorodeoxyglucose positron emission tomography (FDG-PET). Regional cerebral glucose metabolism was compared between groups using an automated aggregate surface-projection algorithm.
What was found
Young adult ε4 carriers and noncarriers did not differ significantly in sex, age, educational level, clinical ratings, or neuropsychological test scores. PET imaging showed that ε4 carriers had abnormally low rates of glucose metabolism bilaterally in the posterior cingulate, parietal, temporal, and prefrontal cortex compared to noncarriers. Quantitative metabolic values and effect sizes were not reported in the abstract.
Why it matters
This study demonstrates that functional metabolic reductions in brain regions vulnerable to Alzheimer's disease are present in APOE ε4 carriers during early adulthood, decades before the typical age of onset for dementia.
Limits
The sample size is very small (12 carriers, 15 controls). The cross-sectional design cannot determine if metabolic differences reflect lifelong traits or progressive neurodegeneration, nor does it establish who will develop dementia. Numerical effect sizes and p-values were omitted from the abstract.
Cited by
- supports Brain metabolic changes detectable by fluorodeoxyglucose (FDG) PET occur in people's 30s and 40s, preceding Alzheimer's cognitive symptoms by two to three decades.