Study challenges the “seductive” amyloid hypothesis of Alzheimer’s disease (AD)

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Vas­cu­lar Health at Age 36 Tied to Brain Health at 70 (Med­page Today):

“A lon­gi­tu­di­nal study shed light on just how ear­ly peo­ple may want to start doing some­thing to reduce their demen­tia risk decades in the future.

Each 1% increase in Fram­ing­ham vas­cu­lar risk score at age 36 was asso­ci­at­ed with 9% high­er white mat­ter hyper­in­ten­si­ty vol­ume … (how­ev­er) Vas­cu­lar risk scores were not linked to beta-amy­loid sta­tus at any point.

“There is increas­ing evi­dence that vas­cu­lar risk fac­tors impact on an indi­vid­u­al’s risk for devel­op­ing demen­tia and may be mod­i­fi­able,” Schott said. “This study pro­vides yet more evi­dence that midlife car­dio­vas­cu­lar risk has neg­a­tive con­se­quences on brain health many years lat­er, but may not do so via the depo­si­tion of beta-amyloid.”

(Sud­ha Seshadri, MD, of the Uni­ver­si­ty of Texas Health in San Anto­nio) added that “In short, these data from the Insight 46 study make a strong case for address­ing vas­cu­lar risk as ear­ly as the fourth decade of life; strength­en the case for study­ing ado­les­cent, ear­ly-child­hood, and peri­na­tal fac­tors as fac­tors asso­ci­at­ed with demen­tia; and warn that effec­tive pre­ven­tion of demen­tia in our time will like­ly require extend­ing think­ing well beyond the seduc­tive amy­loid hypoth­e­sis and the cur­rent empha­sis on elder­ly patients as the best tar­get for pre­ven­tive interventions”.

The Study:

Asso­ci­a­tions Between Vas­cu­lar Risk Across Adult­hood and Brain Pathol­o­gy in Late Life: Evi­dence From a British Birth Cohort (JAMA Neu­rol­o­gy). From the abstract:

• Impor­tance:  Midlife vas­cu­lar risk bur­den is asso­ci­at­ed with late-life demen­tia. Less is known about if and how risk expo­sure in ear­ly adult­hood influ­ences late-life brain health.
• Objec­tive:  To deter­mine the asso­ci­a­tions between vas­cu­lar risk in ear­ly adult­hood, midlife, and late life with late-life brain struc­ture and pathol­o­gy using mea­sures of white matter–hyperintensity vol­ume, ?-amy­loid load, and whole-brain and hip­pocam­pal volumes.
• Design, Set­ting, and Par­tic­i­pants:  This prospec­tive lon­gi­tu­di­nal cohort study, Insight 46, is part of the Med­ical Research Coun­cil Nation­al Sur­vey of Health and Devel­op­ment, which com­menced in 1946. Par­tic­i­pants had vas­cu­lar risk fac­tors eval­u­at­ed at ages 36 years (ear­ly adult­hood), 53 years (midlife), and 69 years (ear­ly late life) … Par­tic­i­pants with at least 1 avail­able imag­ing mea­sure, vas­cu­lar risk mea­sure­ments at 1 or more points, and no demen­tia were includ­ed in analyses.
• Con­clu­sions and Rel­e­vance:  High­er vas­cu­lar risk is asso­ci­at­ed with small­er whole-brain vol­ume and greater white matter–hyperintensity vol­ume at age 69 to 71 years, with the strongest asso­ci­a­tion seen with ear­ly adult­hood vas­cu­lar risk. There was no evi­dence that high­er vas­cu­lar risk influ­ences amy­loid depo­si­tion, at least up to age 71 years. Reduc­ing vas­cu­lar risk with appro­pri­ate inter­ven­tions should be con­sid­ered from ear­ly adult­hood to max­i­mize late-life brain health.

The Study in Context:

• Cog­ni­tive train­ing, diet, exer­cise, and vas­cu­lar man­age­ment seen to improve cog­ni­tion even in peo­ple with genet­ic pre­dis­po­si­tion for demen­tia (APOE e4)
• New stud­ies rein­force Edu­ca­tion and Cog­ni­tive Reserve –instead of drugs tar­get­ing beta amy­loid– as most promis­ing avenue to pro­long cog­ni­tive health and reduce demen­tia risk
• Study: 46.7 mil­lion Amer­i­cans have Alzheimer’s Dis­ease brain pathol­o­gy today, so it’s urgent to pre­vent or at least delay pro­gres­sion to clin­i­cal disease
• Report: 35% of world­wide demen­tia cas­es could be pre­vent­ed by mod­i­fy­ing these 9 mod­i­fi­able risk factors