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How do genetics impact early intervention for dementia?

Researchers investigated whether lifestyle interventions were effective to prevent dementia in those with a genetic predisposition to Alzheimer’s disease.

Cardiovascular and neurological diseases, such as dementia, have been linked to dysfunction of a variation of the apolipoprotein E, or APOE, gene, called the APOE ε4 allele. In fact, people who are carriers of the APOE ε4 allele have been shown to have a reduced amount of cortical gray matter in regions affected by Alzheimer’s disease. These people are also more susceptible to the detrimental effects of environmental risk factors. Because good overall health is thought to improve the condition of Alzheimer’s, lifestyle changes are assumed to be a good intervention, which may combat the effects of APOE-related genetic susceptibility for those at risk for dementia.

The FINGER Trial for Dementia

The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) evaluated whether the effectiveness of lifestyle modifications for those at risk of Alzheimer’s disease would be different for those with or without the APOE ε4 gene. This was a clinical trial including 60 to 77-year-old individuals from the general population in Finland who were at-risk for cardiovascular diseases and dementia. The results were recently published in JAMA Neurology.

Lasting two years, a total of 1,260 participants were identified as having an average or lower than average cognition level and were capable of cooperating safely during intervention practices.  The intervention group was provided with specialized cognitive training, diet, exercise, and vascular management, whereas the control group received regular health advice only. Both groups were given oral and written information that consisted of advice on a healthy lifestyle and all participants were informed on the benefits of diet physical, cognitive, and social activities for vascular risk management and disability prevention. The researchers performed genomic DNA tests from blood samples to identify the presence of APOE ε4 and neuropsychological tests to determine cognition outcomes of all participants over the course of 24 months.

Lifestyle interventions improved outcomes for those with APOE ε4

The results showed that cognition levels improved for those who participated in the intervention groups. The lifestyle interventions proved effective for those with and without the APOE ε4 gene. These results indicate that even those with a genetic predisposition for dementia can benefit from targeted lifestyle modifications. In fact, those who with the genetic susceptibility may have received additional benefits, however, further research will be needed to confirm these results. These findings emphasize the importance of early active interventions.

Interestingly, the results from this clinical trial suggest that making healthy lifestyle changes can be beneficial for cognition in older adults who are at risk of Alzheimer’s disease. These changes show promise for the condition even when individuals are found to have an APOE-related genetic susceptibility to dementia. However, more investigation needs to be done to determine if these lifestyle changes are more pronounced in APOE ε4 carriers.  This investigation brings to light the importance of early prevention strategies that may target multiple modifiable risk factors for people susceptible to dementia.

Written by Viola Lanier, PhD MSc

Reference: Alina Solomon, MD, PhD; Heidi Turunen, BM; Tiia Ngandu, MD, PhD; Markku Peltonen, PhD; Esko Levälahti, MSc; Seppo Helisalmi, PhD; Riitta Antikainen, MD, PhD; Lars Bäckman, PhD; Tuomo Hänninen, PhD; Antti Jula, MD, PhD; Tiina Laatikainen, MD, PhD; Jenni Lehtisalo, MSc; Jaana Lindström, PhD; Teemu Paajanen, MA, Psy; Satu Pajala, PhD; Anna Stigsdotter-Neely, PhD; Tim. Effect of the Apolipoprotein E Genotype on Cognitive Change During aMultidomain Lifestyle Intervention A Subgroup Analysis of a Randomized Clinical Trial. JAMA Neurology. January 2018.



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