Study: High Cognitive Reserve (CR) seen to significantly lower dementia risk even in the presence of high Alzheimer’s Disease (AD) neuropathology

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Fig­ure 2. Inci­dence Rates of Demen­tia per 1000 Per­son-Years by Cog­ni­tive Reserve (CR) Ter­tile and Brain Pathol­o­gy; adjust­ed for age, sex, smok­ing, alco­hol con­sump­tion, phys­i­cal activ­i­ty, body mass index, heart dis­ease, hyper­ten­sion, cere­brovas­cu­lar dis­ease, dia­betes, and apolipopro­tein E e4. AD indi­cates Alzheimer dis­ease. Source: Xu H et al (2020)

Lifes­pan Cog­ni­tive Reserve—A Secret to Cop­ing With Neu­rode­gen­er­a­tive Pathol­o­gy (JAMA Neu­rol­o­gy editorial):

Giv­en the lim­it­ed suc­cess of ther­a­peu­tic inter­ven­tions for Alzheimer dis­ease, there is increased inter­est in under­stand­ing whether mod­i­fi­able fac­tors can help cope with or post­pone the appear­ance of brain pathol­o­gy. It is esti­mat­ed that about 35% of Alzheimer risk is mod­i­fi­able. Epi­demi­o­log­ic stud­ies have shown that life­time expo­sures to high­er edu­ca­tion, high­er occu­pa­tion­al attain­ment, and cog­ni­tive­ly stim­u­lat­ing activ­i­ties are asso­ci­at­ed with reduced risk of Alzheimer demen­tia. Autop­sy stud­ies have shown interindi­vid­ual dif­fer­ences in the amount of brain pathol­o­gy peo­ple can tol­er­ate before man­i­fest­ing cog­ni­tive impair­ments, and autop­sied brains of about one-third of indi­vid­u­als who are cog­ni­tive­ly nor­mal meet neu­ropatho­log­i­cal cri­te­ria for Alzheimer disease.

About a decade ago, the con­cept of cog­ni­tive reserve was pro­posed to account for the dis­crep­an­cy between brain pathol­o­gy and cog­ni­tive sta­tus. The broad hypoth­e­sis was that indi­vid­u­als with enriched life­long expo­sures would be able to bet­ter tol­er­ate with brain pathol­o­gy in late life. Many stud­ies have inves­ti­gat­ed how one can cope with brain dam­age using prox­ies of neu­rode­gen­er­a­tion or synap­tic integri­ty. How­ev­er, the gold stan­dard for test­ing the reserve hypoth­e­sis is the direct mea­sure­ment of brain pathol­o­gy at autop­sy. Keep read­ing (requires subscription)

The Study:

Asso­ci­a­tion of Lifes­pan Cog­ni­tive Reserve Indi­ca­tor With Demen­tia Risk in the Pres­ence of Brain Patholo­gies (JAMA Neu­rol­o­gy). From the abstract:

  • Objec­tive: To exam­ine the asso­ci­a­tion of lifes­pan CR with demen­tia risk, tak­ing brain patholo­gies into account.
  • Design, set­ting, and par­tic­i­pants: This study used data from 2022 par­tic­i­pants in the Rush Mem­o­ry and Aging Project, an ongo­ing com­mu­ni­ty-based cohort study with annu­al fol­low-up from 1997 to 2018 (mean fol­low-up, 6 years; max­i­mum fol­low-up, 20 years) … Dur­ing fol­low-up, 611 died and under­went autop­sies. Data were ana­lyzed from May to Sep­tem­ber 2018.
  • Expo­sures: Infor­ma­tion on CR fac­tors (edu­ca­tion; ear­ly-life, midlife, and late-life cog­ni­tive activ­i­ties; and social activ­i­ties in late life) was obtained at base­line. Based on these fac­tors, lifes­pan CR scores were cap­tured using a latent vari­able from a struc­tur­al equa­tion mod­el and was divid­ed into ter­tiles (low­est, mid­dle, and highest).
  • Results: … The high­est CR score ter­tile was asso­ci­at­ed with a reduc­tion in demen­tia risk, even among par­tic­i­pants with high Alzheimer dis­ease pathol­o­gy (HR, 0.57; 95% CI, 0.37–0.87) and any gross infarcts (HR, 0.34; 95% CI, 0.18–0.62).
  • Con­clu­sions and rel­e­vance: High lifes­pan CR is asso­ci­at­ed with a reduc­tion in demen­tia risk, even in the pres­ence of high brain patholo­gies. Our find­ings high­light the impor­tance of lifes­pan CR accu­mu­la­tion in demen­tia prevention.

The Study in Context: