1. מחלת אלצהיימר: עבר, הווה ועתיד
פרופ' עמוס קורצ'ין
יו"ר המועצה המדעית
עמדא 1 1

2. Most common causes of dementia
Alzheimer’s diseases
Vascular dementias
Frontotemporal dementias
Synuclein dementias 2 2

3. Alzheimer’s disease
A clinico-pathological entity of progressive dementia with specific neuropathological changes.
It is a complex problem!

4. Looking for the magic bullet:
Complex problems have many simple solutions, all of which are wrong.
Cholinergic loss
Trophic factors loss
Aluminum toxicity
Calcium excitotoxicity
Oxidative stress
Glutamate toxicity
Tau hyperphosphorylation
Amyloid toxicity 4 4

5. The past

6. Alzheimer’s Disease: History
Presenile dementia
versus
“cerebral arteriosclerosis”
Alois Alzheimer 6 6

7. ITG
β-amyloid IHC
80 µm
cerebellum
β-amyloid IHC
200 µm

8. The simple solutions are based on incorrect assumptions

10. Drug giants give up on Alzheimer's cure
The INDEPENDENT
Drug giants give up on Alzheimer's cure
Research too difficult and costly, say pharmaceutical companies
Jeremy Laurance
Wednesday, 19 September 2012

11. Spectacular failure over 20+ years!!!

12. The present

13. Characteristic histologic changes define Alzheimer’s disease
Incorrect assumption:
Characteristic histologic changes define Alzheimer’s disease
Neuritic plaques
Neurofibrillary tangles
Are we losing the big picture?

14. 14

15. What about cell loss? Synaptic degeneration? White matter lesions?

16. (Almost) all dementia is mixed dementia16 16

17. The future

18. Sporadic AD, a multifactorial disease
A complex progressive neurodegenerative disorder Caused by a heterogeneous combination of environmental and genetic factors Because of its complexity and etiological heterogeneity it is not a “disease” in the classical sense

19. Extrinsic Causes Intrinsic Causes Senile dementia19 19

20. What needs to be done?

21. Identify the vulnerable
First and foremost:
Treat risk factors!
Identify the vulnerable

22. Established risk factors for senile dementia
Age
Female sex
Low level of education
Severe head trauma
Depression
APOE ε4

23. Vascular risk factors for senile dementia
Hypertension
Atherosclerosis
Diabetes mellitus
Smoking
Hyperhomocysteinemia
Dyslipidemia
Physical inactivity 23 23 23

24. Importance of cognitive reserve
Life style factors
Intellectual stimulation
Preventing social isolation 24 24

25. Negelected risk factors
Hypotension
Sleep apnea
Hearing loss
Stress 25 25

26. Advanced directives

27. We need to look after the victims!27

28. Who is responsible?
Who will take care?

29. Can we trust the government?

30. Role of the civil society

31. Protect the caregivers
Implementation of the national program
Execute prevention program
Enhance social engagement
Protect the caregivers

32. Thank you for your attention