1. Summer School on Neuroscience & Aging
Venice, June 2013
Prevention of the dementing disorders: from observation to intervention
Laura Fratiglioni

2. Outline Part I (30 min +10 for discussion)
Methodological issues: clinical and epidemiological
A model for dementia development
Part II (30 min +10 for discussion)
3. Risk factors
4. Protective factors
5. Summary-current knowledge
Part III (20 min +10 for discussion)
6. Future perspectives
31 December 2018
Laura Fratiglioni

3. METHODOLICAL ISSUES IN THE EPIDEMIOLOGY OF DEMENTIA
PART I
METHODOLICAL ISSUES IN THE EPIDEMIOLOGY OF DEMENTIA
PROTECTING THE HUMAN BRAIN AND REDUCING THE RISK OF DEMENTIA
Laura Fratiglioni
Laura Fratiglioni

4. Epidemiology of Dementia & AD: Topics
Descriptive epidemiology
Etiological epidemiology
Clinical epidemiology
Occurrence Public health
Etiology Risk factors
Diagnosis Markers
Prognosis Natural history
Laura Fratiglioni
31 December 2018 3

5. Dementia: challenging issues
Disease of the older people
Diagnostic validity
Underreport in official statistics
Hospitalization for selected cases
Slow and insidious onset
Presence of co-morbidity
Multifactorial
Lifespan risk
Laura Fratiglioni
31 December 2018 3

6. Disease of the older people
Laura Fratiglioni
31 December 2018 3

7. Disease of the older people
Drop-outs due weakness and disease
Attrition both at baseline and follow-up
Misclassification of the exposure, especially in case control studies - recall bias - unbalance exposure assessment
Competing risk of death
Laura Fratiglioni
31 December 2018 3

8. The Kungsholmen Project
Baseline
1st
follow-up
2nd
follow-up
3rd
follow-up
4th
follow-up 1

9. The Kungsholmen Project
1810
Participants
23.6%
Drop-outs
1099
Participants
24%
Deceased
15.5%
Drop-outs
680
Participants
33%
Deceased 5%
Drop-outs
421
Participants
32%
Deceased 6%
Drop-outs
265
Participants
30%
Deceased 7%
Drop-outs
Baseline
1st
Follow-up
2nd
Follow-up
3rd
Follow-up
4th
Follow-up 1

10. Dementia: challenging issues
Disease of the older people
Diagnostic validity
Underreport in official statistics
Hospitalization for selected cases
Slow and insidious onset
Presence of co-morbidity
Multifactorial
Lifespan risk
Laura Fratiglioni
31 December 2018 3

11. Diagnostic validity
No biological markers Variability Missing mild/early cases
Selection bias
Misclassification of the outcome
decreased power bias
Laura Fratiglioni
31 December 2018 3

12. Rethinking the classification of degenerative and vascular cases
One challenge is the overlapping between AD and VaD. 55% mixed; AD with vascular involvment or VaD with AD type of course. 75+
Viswanathan, Rocca, Tzourio, Neurology, May 2009
Kalaria R et al. Alzheimer Dis Assoc Disord 1999
Aguero-Torres et al, 2001 12 12

13. Distribution of dementia subtypes: incident cases
MIXED DEMENTIA
Longitudinal studies on dementia in Europe
(Fratiglioni et al, Neurology 2000)
Distribution of dementia subtypes: incident cases
MIXED CASES
Aguero-Torres, 2001

14. Neuropathology of Alzheimer Disease and MCI Schneider et al Ann Neurol 2009
Mixed dementia

15. Age, Neuropathology, and Dementia Savva et al, NEJM 2009
Mixed dementia

16. Dementia: challenging issues
Disease of the older people
Diagnostic validity
Underreport in official statistics
Hospitalization for selected cases
Slow and insidious onset
Presence of co-morbidity
Multifactorial
Lifespan risk
Laura Fratiglioni
31 December 2018 3

17. Underreport in official statistics
Population
IPR + CDR
Prevalent cases KP
50.2 ( )
Incident cases KP
47.9 ( )
Prev. cases SNAC-K
42.1 ( )
Laura Fratiglioni
31 December 2018 3

18. Dementia: challenging aspects
Underreport in official statistics
Hospitalization for selected cases
Selection bias
Misclassification of the outcome decreased power bias
Laura Fratiglioni
31 December 2018 3

19. Dementia: challenging issues
Disease of the older people
Diagnostic validity
Underreport in official statistics
Hospitalization for selected cases
Slow and insidious onset
Presence of co-morbidity
Multifactorial
Lifespan risk
Laura Fratiglioni
31 December 2018 3

20. CIND

21. Social network and AD STUDY POPULATION Detection of incident cases
Fratiglioni et al, Lancet 2000
STUDY POPULATION
Detection of
incident cases
Assessment of
social network
1203 non-demented persons
176 demented subjects
Baseline
1st follow-up

22. Leisure activities & dementia Wang et al, Am J Epidemiol 2002
STUDY POPULATION
Assessment of
engagement in
leisure activities
Detection of
incident cases
776 non demented
123
demented
Baseline
1st follow-up
2nd follow-up

23. Dementia: challenging aspects
Slow and insidious onset
Precipitating rather than risk factors
Reverse causality
Laura Fratiglioni
31 December 2018 3

24. Dementia: challenging issues
Disease of the older people
Diagnostic validity
Underreport in official statistics
Hospitalization for selected cases
Slow and insidious onset
Presence of co-morbidity
Multifactorial
Lifespan risk
Laura Fratiglioni
31 December 2018 3

25. 54.8% Multimorbidity (2+ diseases)
Most common chronic disorders among old people
Multimorbidity
(2+ diseases)
54.8%
( )
Marengoni et al,
Am J Publ Health 2008

26. Age-specific prevalence per 100 for number of chronic diseasesNo
diseases %

27. Dementia: challenging issues
Disease of the older people
Diagnostic validity
Underreport in official statistics
Hospitalization for selected cases
Slow and insidious onset
Presence of co-morbidity
Multifactorial
Lifespan risk
Laura Fratiglioni
31 December 2018 3

28. Brain Reserve Capacity
Risk Factors: biological &
contextual
Vascular
mechanisms
Neuro-
degeneration
Toxicity
Oxidative
stress
Inflammation
Genetic background
Birth Childhood- Adult life- Older
2nd decade Middle age Transition age
Brain lesions 20 60 75
Brain Reserve Capacity
Psychosocial
factors
Nutrition
Protective Factors

29. Dementia: challenging aspects
Disease of the older people
Questionable diagnostic validity
Underreport in official statistics
Hospitalization for selected cases
Slow and insidious onset
Presence of co-morbidity
Multifactorial
Life span
Life time cumulative exposure
Exposure windows
Laura Fratiglioni
31 December 2018 3

30. Dementia: challenging aspects
Disease of the older people
Questionable diagnostic validity
Underreport in official statistics
Hospitalization for selected cases
Slow and insidious onset
Presence of co-morbidity
Multifactorial
Lifespan risk
Study population
Study design
Drop-outs
Case detection
Diagnosis
Exposure
Confounders
Bias
Power
Temporal relation 3

31. Epidemiological evidence in dementia
SBU 2005
Wang & Fratiglioni JAD 2007
Internal validity index 4 grades (not-acceptable; low, medium; high)
9 items (Population types, Design,Drop-outs, Case detection, Diagnosis,Exposure, Confounders, Bias, Power)
Causal criteria index 4 grades (not-acceptable; low, medium; high) 3 items (Strength, Temporality, Biolog. gradient)

32. Epidemiological evidence in dementia
Grading the evidence
Quantity
Low
Medium
High
Insufficient
Limited
Moderate
Substantial
Strong
Final quality index

33. Questions