Imagine Alzheimer’s as a complex puzzle. Researchers have discovered a new piece of that puzzle called the polygenic hazard score (PHS). This score reveals a person’s genetic risk for developing Alzheimer’s disease and can shed light on early identification. In a recent study, scientists investigated how PHS interacts with another key puzzle piece: hippocampal subfield atrophy and its impact on episodic memory in older adults. They found that individuals with high PHS and lower hippocampal subfield volume ratio performed worse on episodic memory tests. This effect was particularly evident among those diagnosed with mild cognitive impairment (MCI). Interestingly, the study also suggested that the hippocampal subfield volume ratio might serve as a mediator between genetic risk and memory performance in people with MCI. These findings highlight the crucial role of genetics and brain structure in Alzheimer’s disease progression. To learn more about this groundbreaking research, dive into the full article!

BackgroundUnderstanding genetic influences on Alzheimer’s disease (AD) may improve early identification. Polygenic hazard score (PHS) is associated with the age of AD onset and cognitive decline. It interacts with other risk factors, but the nature of such combined effects remains poorly understood.Materials and methodsWe examined the effect of genetic risk and hippocampal atrophy pattern on episodic memory in a sample of older adults ranging from cognitively normal to those diagnosed with AD using structural MRI. Participants included 51 memory unimpaired normal control (NC), 69 mild cognitive impairment (MCI), and 43 AD adults enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Hierarchical linear regression analyses examined the main and interaction effects of hippocampal subfield volumes and PHS, indicating genetic risk for AD, on a validated episodic memory composite score. Diagnosis-stratified models further assessed the role of PHS.ResultsPolygenic hazard score moderated the relationship between right fimbria/hippocampus volume ratio and episodic memory, such that patients with high PHS and lower volume ratio had lower episodic memory composite scores [ΔF = 6.730, p = 0.011, ΔR2 = 0.059]. This effect was also found among individuals with MCI [ΔF = 4.519, p = 0.038, ΔR2 = 0.050]. In contrast, no interaction effects were present for those NC or AD individuals. A follow-up mediation analysis also indicated that the right fimbria/hippocampus volume ratio might mediate the link between PHS and episodic memory performance in the MCI group, whereas no mediation effects were present for those NC or AD individuals.ConclusionThese findings suggest that the interaction between AD genetic risk and hippocampal subfield volume ratio increases memory impairment among older adults. Also, the results highlighted a potential pathway in which genetic risk affects memory by degrading hippocampal subfield volume ratio in cognitive decline subjects.

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