Agenda Alzheimers The Looming Epidemic 1 2 The Fast Future is Here - - PowerPoint PPT Presentation

Alzheimer’s Disease: Foresight is 2020

Denise M Kalos

President & CEO

2018 Concierge Medicine FORUM

Ginger Schechter, MD

Chief Medical Officer

Agenda

10/5/2018 2

1 Alzheimer’s – The Looming Epidemic The Fast Future is Here 2 What’s Trending 2020 – Science or Lifestyle? 3 Tomorrow’s Treatment Today 4

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Life Expectancy Throughout History

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Aging: The Driving Force in CHRONIC Disease

AGING

Stroke Arthritis Cataracts Frailty Heart Disease Type II Diabetes Cancer Neurodegeneration

AD: The facts and figures

There are 5.4 million people with Alzheimer’s in the U.S.; this number will exceed 13 million by 2050. 30 million & 160 million worldwide Every 68 seconds someone is diagnosed with AD. AD costs the U.S. over $180 billion annually. $1.1 trillion in 2050. No truly effective Rx has been developed for AD. While many diseases are on the decline, AD is on the rise.

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Aging and Alzheimer’s

 19% of the population (72.1M people) will be 65 years and older

in 2030, almost double what it was in 2008

 11% of people 65 and older have Alzheimer’s Disease, grows to

32% by age 85

 360,000 new cases of AD are diagnosed annually in US.

75 Million Baby Boomers Flooding the System

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What is Alzheimer’s Disease?

 First described in 1901  Alzheimer’s Foundation Definition of

AD: a progressive degenerative disorder

resulting in loss of memory, thinking and language skills, and behavioral changes

 Two types of abnormal lesions clog

the brain: Beta-amyloid plaques and

neurofibrillary tangles Amyloid Precursor Protein (APP) B-amyloid Plaques Tau Po4-Tau Tangles

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Drug Research: Difficult, Expensive, Complicated

 Exact cause(s) of the disease unknown  Disease manifests very early but early diagnosis not available  Gets worse with other changes  No perfect models of AD exist to recapitulate the disease in humans

 Very complex, multifactorial with too man variables (genetic, lifestyle, environmental)

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AopE4

 2 copies of the ApoE4 allele have 50-80% chance of developing AD  1 copy: 45% chance of developing AD  60-80% of AD patients carry the ApoE4 isoform  Cellular interactions of

ApoE4 affect multiple pathways

 Research offers new

insight

 Research does not target

AD therapeutics

Alzheimer’s Disease: Therapeutic Landscape

 Donepezil (Aricept)  Rivastigmine (Exelon)  Tacrine (Cognex)  Memantine (Namenda)  Galantamine (Razadyne)

APPROVED

 Bapineuzmab  Solanezumab  Alzemed   Flurizan  Semagacestat  Rosiglitazone  Phenserine  Dimebon  Statins  Antioxidant

PHASE 3

 EGCg  ELND005

PHASE 2

 NIC5-15  PBT2  Bryostatin-1  EHT-0202  BMS708163  ABT089  AZD3480  PUFA  PRX03140  NGF  Huperzine-A  EVP6124  MEM3454  PF-04447943  SB742457  AL-108  PF04360365  ACC001  AN1792  CAD106

PHASE 1

 GSK933776  MABT5102A  UB311  R1450  V950  E2012  MK0752  CHF5074  CTS21166  PF3084014  Begacestat  Talsaclidine  AF102B

 Clinical Trial in AD terminated

  Tau aggregation/phosph   Ab production   Ab aggregation   Ab clearance  Others  Cholinergic drugs  Valproate  TTP448  Nicotinamide  Lithium  NP12

“Game of Throwns” (243/244)

Dimebon x2

R.I.P.

Semagacestat

R.I.P.

Rosiglitazone

R.I.P.

Alzhemed

R.I.P.

Rember

R.I.P.

Bapineuzumab

R.I.P.

AN-1792

R.I.P.

Flurizan

R.I.P.

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Any Accurate Theory of AD Should Explain:

 Lack of successful therapeutic development to date  Remarkable diversity of risk factors for AD  High prevalence of AD in the elderly  Mechanism(s) by which ApoE4 increases risk for AD  The physiological role(s) of Ab peptides  The anatomic patter of spread of AD pathology  Why some people (and Transgenic mice) collect large amounts of Ab peptides

with no symptoms of AD

 The relationship between Ab and tau pathology  IS ALZHEIMER’S DISEASE ONE DISEASE?

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Problems with Status Quo

 Minimally effective treatments (Aricept, etc.)  No focus on prevention  High levels of patient & caregiver (and physician) frustration  Almost all drug trials

focused on:

 Amyloid Plaque

prevention or reduction

 Monotherapy  Almost all have either

failed or halted due to unacceptable side effect

Cures

X Prize

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Good News

 Accumulating (10-20+ years of disease research shows there are multiple

modifiable risk factors

 Diet, Lifestyle, Metabolic factors, Vitamin levels, etc.

 Recent use of multi-modality interventions

 Not necessarily pharmaceutical-based  Not only addressing a single factor

Research

Numerous studies over the past 10-20 years have demonstrated the importance of individual modifiable risk factors

→ Untreated mid-life hypertension is

associated with increased risk of Alzheimer’s disease in later life (2000)

→ Both hypothyroidism and

hyperthyroidism are correlated with increased risk of Alzheimer’s disease (2008)

→ Elevated homocysteine levels

are correlated with increased risk for Alzheimer’s disease (2000)

Research

Numerous studies over the past 10-20 years have demonstrated the importance of individual modifiable risk factors

→ Untreated mid-life hypertension is

associated with increased risk of Alzheimer’s disease in later life (2000)

→ Both hypothyroidism and

hyperthyroidism are correlated with increased risk of Alzheimer’s disease (2008)

→ Elevated homocysteine levels

are correlated with increased risk for Alzheimer’s disease (2000)

Buck Institute for Research on Aging – 2014 Study

Buck Institute for Research on Aging – 2014 Study

Pilot study of multi-modality therapy for SCI, MCI or early Alzheimers Disease

Buck Institute for Research on Aging – 2014 Study

• 9 out of 10 patients improved memory (subjectively or by cognitive testing)
• 6 patients had been unable to work or had work difficulties; all 6 either returned to

work or experiences improved work performance

Increasing Scientific Data: multi modality therapy

DATA SLIDE – Need Data from John Q.

• Randomized, controlled clinical trial (2015)
• 1260 at-risk elderly patients
• Significantly improved cognitive function

associated with optimized diet, exercise, cognitive training, and vascular risk monitoring

Increasing Scientific Data: multi modality therapy

• 127 elderly patients with MCI
• Interventions included cognitive stimulation,

Mediterranean diet, fitness training, and meditation

• Improved cognitive performance in 84%

Increasing Scientific Data: multi modality therapy

Scientific American April, 2017

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One Cause: One Solution

36 holes in the roof . . .

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Need a Systematic, Comprehensive Approach

Holistic approach to treatment

The Rise of Personalized Health

Personalized Digital Health chronic disease prevention and medical treatment based on an individual’s physiology, genetic or biochemical profile, value system and unique conditions---will dramatically improve success rates and reduce system costs associated with one-size-fits all health care approaches

10/5/2018

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One Size Fits One - Precision Medicine

• Medical history, genetic and

blood-based biomarker panel multiplex testing

• Personalized therapeutic

plan

• Physician and patient

reporting with physician, dietitian and PT consultation and support

• Ongoing patient monitoring

and clinic visits

From Prescriptions to Preventions

10/5/2018 31

Engaging Consumers in Health Improvement

the vast majority of the devastation and cost of chronic disease is concentrated in higher risk groups who are less informed

• r resistant to behavior

change, and are managed by a harried primary care physician in a fossilized system.

Prevention is Cure!!

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Denise M Kalos dmkalos@affirmativhealth.com Phone: 415-309-3919

Questions?