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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:

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As seen in The New York Times, The Wall Street Journal, BBC News, CNN, Reuters,  SharpBrains is an independent market research firm tracking how brain science can improve our health and our lives.

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