Alzheimers Disease: The Evolving Therapeutic Landscape

1
Alzheimers Disease The Evolving Therapeutic
Landscape

• George T. Grossberg, M.D.
• Samuel W. Fordyce ProfessorDirector, Geriatric
  Psychiatry
• Saint Louis University School of Medicine

2
Disclosure

• Grant/Research Support Abbott Laboratories,
  Cyberonics, Eli Lilly, Forest Laboratories, Inc.,
  Novartis, Organon, ONO, Pfizer, Wyeth
• Consultant Aztra Zeneca, Bristol-Myers Squibb,
  Forest Laboratories, Inc., Janssen, Lundbeck,
  Merz Pharmaceuticals, Novartis, Organon, Pfizer,
  sanofi-aventis, Sepracor, Synthelabo, Wyeth

3
Alzheimers Disease (AD) More Than Just Memory
Loss

• AD is a progressive, degenerative disease
  involving
• Loss of memory and other cognitive functions
• Decline in ability to perform activities of
  daily living
• Changes in personality and behavior
• Increases in resource utilization
• Eventual nursing home placement

4
Alzheimers Disease Overview

• Progressive, degenerative brain disease
  characterized by an increasing loss of memory
  other cognitive functions
• Characterized by changes in activities of daily
  living (ADL), behavior personality, cognition
  including judgment ABCs
• Most common cause of dementia among people aged
  65 or over

5
Current Prevalence of AD

• AD is the fourth leading cause of death due to
  disease for people gt 65 years of age in the
  United States1
• Approximately 4 million people in the United
  States have AD2

1. Murphy SL. Natl Vital Stat Rep.
2000481-106. 2. Evans DA et al. Milbank
Quarterly. 199068267-289.
6
Projected Prevalence of AD
4 Million AD Cases TodayOver 14 Million
Projected Within a Generation
14.3
11.3
8.7
6.8
5.8
4
2
0
Year
Evans DA et al. Milbank Quarterly.
199068267-289.
7
AD Is the Most Prevalent Type of Irreversible
Dementia
VaD, vascular dementia DLB, dementia with Lewy
bodies FTD, frontotemporal dementia. reflects
difficulties diagnosing/reporting dementias
only estimations of prevalencecan be made.
100
80
60
Irreversible dementias ()
40
20
0
AD
VaD
DLB
FTD
Other
Guttman R et al. Arch Fam Med. 19998347-353. McK
eith IG et al. Neurology. 1996471113-1124. Cherr
ier MM et al. J Am Geriatr Soc. 199745579-583.
8
Mortality Due to AD Impact of Age
1,000
10
Rate per 100,000 population
100
1
0.1
0.01
Under45
4554
5564
6574
7584
85
Age (years)
Reprinted with permission from Hoyert DL et al.
Natl Vital Stat Rep. 1999471-104.
9
Cost of AD in the United States

• Annual treatment costs 100 billion
• 18,408/patient per year for mild AD
• 30,096/patient per year for moderate AD
• 36,132/patient per year for severe AD

Leon J et al. Health Aff (Millwood).
199817206-216.
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Does Treatment Affect the Cost of AD?

• Savings are small for mild and very severe AD
• Prevention of even a small decline in cognition
  for patients with moderate AD would save
  3,700 per patient annually
• Relatively small improvements in patients with
  moderate AD would save 7,100 per patient
  annually

Ernst RL et al. Arch Neurol. 199754687-693.
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Who Are the Caregivers?

• The overwhelming majority of patients live at
  home and are cared for by family and friends
• 77 are women
• 73 are over 50 years of age
• 33 are the sole providers
• 45 are children of the patient
• 49 are spouses
• Remainder are close family members or friends

Consumer Health Sciences, LLC. Princeton, NJ
December 1999.
12
Caregiver Burden

• Caregivers spend from 40100 hours per week with
  the patient
• 90 are affected emotionally (frustrated,
  drained)
• 75 report feeling depressed 66 have
  significant depression
• Half say they do not have time for themselves and
  that the stress affects family relations
• Many experience a significant loss of income

Coping. Available at http//www.alzheimers.com.
Accessed September 2000.
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Factors That Create Breaking Point for
Caregiver

• Amount of time spent caring for the patient
• Loss of identity
• Patient misidentifications and clinical
  fluctuations
• Nocturnal deterioration of patient

Annerstedt L et al. Scand J Public Health.
20002823-31.
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Neuropathological Changes Characteristic of AD
AD
Normal
NFT
AP
AP amyloid plaques
NFT neurofibrillary tangles
Courtesy of George Grossberg M.D. St. Louis
University
15
Key Risk Factors for AD

• Primary risk factors
• Age
• Family history
• Genetic marker such as APOE-4,
• trisomy 21, mutations in presenilin 1,2
• Cardiovascular risk factors e.g.
  hyperlipidemia/hypertension (the role of statins
  and omega 3 fatty acids)
• Possible risk factors
• Head trauma
• Low level of education
• Depression
• Increased zinc?
• Increased homocysteine (the role of B-vitamins,
  e.g. Folic acid)

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AD Is Often Misdiagnosed

• Patient initially diagnosed with AD

Patients first diagnosis other than AD
35
14
14
No 72
9
Yes 28
7
21
Dementia (not AD)
Stroke
Depression
No diagnosis
Normal aging
Other
Source Consumer Health Sciences,LLC.
Alzheimers Caregiver Project. 1999.
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Treatment Alternatives

• Symptoms
• Non-pharmacological
• Neuroleptics
• Anti-depressants
• Anti-convulsants
• ChEIs
• NMDA receptor antagonists

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AD Treatment Algorithm

• Stage of AD Mild Moderate
  Severe
• Treatment
• Options ChEI
  ChEI/ Memantine
  Memantine
• (alone or in (alone or
  in
• combination)
  combination)