Aging memory and alzheimer s disease
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Aging, Memory and Alzheimer’s Disease. Kinga Szigeti, MD, PhD. Aging and Alzheimer’s disease. The biggest challenge in AD: it is superimposed on normal aging Insidious onset No blood test; diagnosis is putting a puzzle together. Major Public Health Problem. Single domain amnestic

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Aging, Memory and Alzheimer’s Disease

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Aging, Memory and Alzheimer’s Disease

Kinga Szigeti, MD, PhD


Aging and Alzheimer’s disease

  • The biggest challenge in AD: it is superimposed on normal aging

  • Insidious onset

  • No blood test; diagnosis is putting a puzzle together

Major Public

Health Problem


Single domain amnestic

-Forgetting where we put things

-Forgetting appointments

-Repeatiing questions or conversations

Red-yellow = diff small-diff big

Multidomain Z score <-2

Mild AD MMSE 20-26


PET metabolism and amyloid imaging

Symptoms late in the disease: cells are damaged

We cannot recover nerve cells; goal is to prevent

We need biomarkers before the symptoms start


Alzheimer disease as a model of complex genetics

Not two patients are exactly alike


APP storyMendelian genetics


Amyloid hypothesis


Linkage

Trisomy 21

Partial trisomy 21 not including APP-no AD


Candidate gene: APP

  • Precursor protein to amyloid in AD brain

  • Mutations found

  • Disease and mutation went together within families

  • Interestingly some of these mutations affect sites where gamma cleavage occurs


Linkage

Chr 14

Chr 1


Amyloid hypothesis: genetic confirmation

PSEN1

40 and 42

APP

PSEN2

D

Mutations in APP regulatory sequences


Genetics proves it is heterogeneous


Research at the University at Buffalo

Olfactory receptor association with AD age at onset

Copy number variation

Pieces of chromosomes (genetic material)

Missing or in extra copies


Research at the University at Buffalo

Deletion upstream from CREB1 association with AD


CHRFAM7A association with AD

Raminathan et al,PlosOne

Namenda might work better

is this group


Alzheimer’s disease model: induced pluripotent stem cells


The goal: prevention

  • Age 65 well visit/ part of the prevention panel

  • Primary care physician asks about memory issues

  • Screening memory test

  • Blood test for genetic risk factors (gene chip)

  • Assess family history of dementia

    Then risk stratification:

    Low riskMonitor

    Intermediate riskConsider amyloid imaging then Rx

    High RiskAmyloid imaging then Rx


The goal: personalized treatment

  • If memory problem is present:

  • Clinical workup

  • Gene chip to determine which drugs work best


Until we have the breakthrough: ADMDC patient care

  • Diagnose early

  • Modify risk factors to slow progression

  • Treat to change slope of decline

  • Buys us time

  • Gives years of close to normal life


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