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Cognitive training, diet, exercise, and vascular management seen to improve cognition even in people with genetic predisposition for dementia (APOE e4)

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How do genet­ics impact ear­ly inter­ven­tion for demen­tia? (Med­ical News Bul­letin):

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 e4 allele…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 e4 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 inter­ven­tion group was pro­vid­ed with spe­cial­ized cog­ni­tive train­ing, diet, exer­cise, and vas­cu­lar man­age­ment, where­as the con­trol group received reg­u­lar health advice only…The researchers per­formed genom­ic DNA tests from blood sam­ples to iden­ti­fy the pres­ence of APOE ?4 and neu­ropsy­cho­log­i­cal tests to deter­mine cog­ni­tion out­comes of all par­tic­i­pants over the course of 24 months.

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 e4 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.”

The Study

Effect of the Apolipopro­tein E Geno­type on Cog­ni­tive Change Dur­ing a Mul­tido­main Lifestyle Inter­ven­tion: A Sub­group Analy­sis of a Ran­dom­ized Clin­i­cal Tri­al (JAMA Neu­rol­o­gy). From the abstract:

  • OBJECTIVE: To exam­ine whether the APOE e4 allele mod­i­fies the pre­vi­ous­ly report­ed sig­nif­i­cant cog­ni­tive ben­e­fits of a mul­tido­main lifestyle inter­ven­tion (pre­spec­i­fied sub­group analy­sis).
  • DESIGN, SETTING, AND PARTICIPANTS: The Finnish Geri­atric Inter­ven­tion Study to Pre­vent Cog­ni­tive Impair­ment and Dis­abil­i­ty (FINGER) was a ran­dom­ized clin­i­cal tri­al in 6 cen­ters across Fin­land (screen­ing and ran­dom­iza­tion per­formed from Sep­tem­ber 7, 2009, through Novem­ber 24, 2011; inter­ven­tion dura­tion, 2 years). Data analy­sis was per­formed from August 1, 2015, to March 31, 2016. The study pop­u­la­tion was at-risk old­er indi­vid­u­als from the gen­er­al pop­u­la­tion. Inclu­sion cri­te­ria were age of 60 to 77 years; Car­dio­vas­cu­lar Risk Fac­tors, Aging, and Demen­tia risk score of at least 6 points; and cog­ni­tion at a mean lev­el or slight­ly low­er than expect­ed for age. Indi­vid­u­als with demen­tia or sub­stan­tial cog­ni­tive impair­ment and con­di­tions that pre­vent­ed coop­er­a­tion or safe engage­ment in the inter­ven­tion were exclud­ed. APOE geno­type data were avail­able for 1175 of the 1260 par­tic­i­pants.
  • INTERVENTIONS: Par­tic­i­pants were ran­dom­ly assigned in a 1:1 ratio to a mul­tido­main inter­ven­tion group (diet, exer­cise, cog­ni­tive train­ing, and vas­cu­lar risk man­age­ment) or a con­trol group (gen­er­al health advice). Group allo­ca­tion was not active­ly dis­closed to par­tic­i­pants, and out­come asses­sors were masked to group allo­ca­tion.
  • MAIN OUTCOMES AND MEASURES: Pri­ma­ry out­come was change in cog­ni­tion mea­sured through a com­pre­hen­sive neu­ropsy­cho­log­i­cal test bat­tery. Analy­sis was based on mod­i­fied inten­tion to treat (par­tic­i­pants with at least 1 post base­line assess­ment).
  • RESULTS: A total of 1109 par­tic­i­pants were includ­ed in the analy­sis: 362 APOE e4 allele car­ri­ers (173 inter­ven­tion and 189 con­trol) and 747 non­car­ri­ers (380 inter­ven­tion and 367 con­trol). The APOE e4 car­ri­ers and non­car­ri­ers were not sig­nif­i­cant­ly dif­fer­ent at base­line (except for serum cho­les­terol level)…Intervention effect was not sig­nif­i­cant­ly dif­fer­ent between car­ri­ers and non­car­ri­ers.
  • CONCLUSIONS AND RELEVANCE: Healthy lifestyle changes may be ben­e­fi­cial for cog­ni­tion in old­er at-risk indi­vid­u­als even in the pres­ence of APOE-relat­ed genet­ic sus­cep­ti­bil­i­ty to demen­tia. Whether such ben­e­fits are more pro­nounced in APOE e4 car­ri­ers com­pared with non­car­ri­ers should be fur­ther inves­ti­gat­ed. The find­ings also empha­size the impor­tance of ear­ly pre­ven­tion strate­gies that tar­get mul­ti­ple mod­i­fi­able risk fac­tors simul­ta­ne­ous­ly.

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