Can early intervention prevent progression to dementia

1
Can early intervention prevent progression to
dementia?

• Henry Brodaty
• Professor of Aged Care Mental Health
• Director, Dementia Collaborative Research Centre,
  University of New South Wales
• Katrin Seeher
• Research Psychologist, POWH UNSW

2
Outline

• Importance of delay in progression
• Interventions
• Pharmacotherapy
• Nutritional
• Psychosocial
• Lifestyle
• Conclusions

3
Outline

• Importance of delay in progression
• Interventions
• Pharmacotherapy
• Nutritional
• Psychosocial
• Lifestyle
• Conclusions

4
Prevalence and rate of MCI progression to
dementia from epidemiological studies

• Prevalence varies between 3 and 19
• Incidence per 1000 per year 8-58
• Conversion to dementia after 2 yrs 11-33
• Conversion to dementia after 5 yrs gt50

Gauthier et al (2006). Lancet. 3671262-1270
5
Postponement between MCI and manifest dementia

• Short-term economic benefits
• US 5300 per patient per year

Wimo Winblad (2003). Acta Neurol Scand. 107
(Suppl 179)94-99
6
Delay prevention

• If onset of AD can be delayed
• by 2 yrs, ? prevalence by gt20
• by 5 yrs, ? prevalence by 501

1Brookmeyer et al. (1998)
7
Outline

• Importance of delay in progression
• Interventions
• Pharmacotherapy
• Nutritional
• Psychosocial
• Lifestyle
• Conclusions

8
Pharmacotherapy for MCI
9
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10
Currently completed or ongoing clinical trials
for MCI from www.clinicaltrials.gov
11
Ongoing clinical trials for MCI
From www.clinicaltrials.gov
12
Drugs under investigation for MCI
Ongoing studies
Completed studies

• Donepezil
• Levodopa
• Melatonin
• AQW051
• S18986
• Nicotine patch
• Ginkgo

• Pioglitazone
• Metformin
• Regular insulin
• Rosiglitazone
• Testosterone
• TH9507 GHRH

• Rivastigmine
• Galantamine
• Donepezil
• Piracetam
• Ampalex
• AL-108/208

From www.clinicaltrials.gov
13
Management of MCI First approaches

• 1st wave of clinical trials
• Aim symptomatic drug treatment for amnestic MCI
• Duration 6 mths to 3 yrs
• Results largely unsuccessful ?

Gauthier (2004). Dialogues Clin Neurosci.
6391-395
14
Galantamine
15
Galantamine for MCI

• Two 24-mths DB RCTs
• Placebo vs 16mg vs 24 mg galantamine
• 2048 Ss (n1990, n21058)
• CDR 0.5 (CDR memory 0.5)
• Primary outcome conversion to dementia
• Secondary outcomes CDR-SB, ADAS-cog/MCI,
  ADCS-ADL/MCI, DSST

Winblad et al (2008). Neurology. 702024-2035
16
Galantamine for MCI results

• Conversion to dementia
• CDR-SB
• Study 1
• Study 2
• ADAS-cog/MCI and ADCS-ADL/MCI
• Digit Symbol Substitution Test
• Study 1
• Study 2

n.s.
Galantamine gt Placebo at 12 24mths
n.s.
n.s.
Galantamine gt Placebo at 12 mths
Galantamine gt Placebo at 24 mths
Winblad et al (2008). Neurology. 702024-2035
17
Galantamine for MCI
Study 1
Study 2
Winblad et al (2008) Neurology 702024-2035
18
Galantamine trial for MCI

• Study objectives
• Prevent development of AD
• Effects on cognition and global function
• Treatments
• Galantamine 16 or 24 mg/day
• Placebo
• 2-year duration
• 50 years old and over
• 2057 elderly (17 countries)

19
Galantamine trial for MCI
-0.8

p H0.05 vs baseline p H0.01 vs baseline


p H0.05 vs placebo p H0.01 vs placebo
p H0.01 vs baseline p H0.002 vs baseline



-0.6



-0.4








-0.2
Improvement in CDR-SB
Mean (SEM) change from baseline
0







0.2





0.4





0.6
0.8
24
21
18
15
12
9
6
3
Baseline
Month
20
Rate of change in whole brain volume Rate of
brain atrophy over 24 months in galantamine vs
placebo
Males
Total
Females
Placebo (n142), galantamine (n127), p0.003,
plt0.001 with sex (additional covariate) Placebo
(n59), galantamine (n70), plt0.001,
Placebo(n83), galantamine (n57), p0.145
21
Donepezil
22
Efficacy of donepezil in MCI

• 24-wk DB RCT
• 270 Ss with MCI
• donepezil (10mg) vs placebo
• Main outcome measures
• NYU paragraph delayed recall test
• ADCS CGIC-MCI
• Secondary outcome measures
• ADAS-Cog, Patient Global Assessment,
  neuropsychologic measures, AEs

Salloway et al (2004). Neurology.63651-657
23
Efficacy of donepezil in MCI results
n.s.

• NYU paragraph delayed recall test
• ADCS CGIC-MCI
• ADAS-Cog (mean change from baseline)
• Patient Global Assessment
• neuropsychological measures

n.s. for ITT and FE
donepezil gt placebo (plt0.01)
n.s. for ITT, but sig for OC and Fully Evaluable
inconclusive
Salloway et al (2004). Neurology.63651-657
24
Safety of donepezil in MCI results
Salloway et al (2004). Neurology.63651-657
25
Safety of donepezil in MCI results

• Most AEs transient and mild or moderate
• Discontinuation due to AEs donepezil gt placebo
• 11 SAEs (5 donepezil and 6 placebo)
• ? 1 (atrial fibrillation) rated as possibly
  related to study medication

Salloway et al (2004). Neurology.63651-657
26
May donepezil delay progression to AD in MCI
patients?

• 3-yr DB RCT with parallel-group design
• 769 Ss with amnestic MCI
• 10mg donepezil vs 2000 IU VitE vs placebo
• Main outcome measure
• time to progression to AD
• Secondary outcome measures
• MMSE, ADAS-Cog, CDR-(SB), ADCS, GDS,
  neuropsychological battery

Petersen et al (2005).N Eng J Med.352(23)2379-238
8
27
Vitamin E Conversion to AD in MCI trial
1 yr
2 yr
3 yr
1.0
0.9
0.8
Probability of not converting to AD
0.7
0.6
0.5
DP P0.416 EP P0.912
0.4
400
200
0
600
800
1,000
1,200
Time on MCI study (days)
CP1157990-7
28
Post-hoc analysis Progression to AD in donepezil
vs placebo group
Only significant at 6 and 12 mths
29
APOE e4 predictor for progression to AD
30
Post-hoc analysis Progression to AD in APOE e4
carriers
Donepezil vs placebo p0.04
31
Safety and AEs
as compared to placebo
32
Summary

• 212 Ss ? AD
• Rate of progression per year 16
• Probability of progression n.s.
• Secondary outcomes sig differences confined to
  1st 18 mths
• Post-hoc analysis
• Donepezil group less likely to progress within
  1st yr
• APOE carriers with donepezil gt placebo

Petersen et al (2005).N Eng J Med.352(23)2379-238
8
33
Donepezil for MCI Cochrane Review

• 2 double-blind RPCTs with donepezil for MCI
• too heterogeneous for meta-analysis
• Results
• Little evidence for ?cognitive function
• No evidence that donepezil delays progression to
  AD
• BUT is associated with side effects

Birks Flicker (2008). Cochrane Review
34
Rivastigmine
35
Effect of rivastigmine on delay to Dx of AD
(InDDEx trial)

• 4-yr DB RPCT
• 1018 Ss with MCI
• rivastigmine (3mg/day-12mg/day) vs placebo
• Main outcome measures
• Time to clinical Dx of AD
• Change in performance on cog test battery
• Secondary outcomes MRI changes

Feldman et al (2007) Lancet Neurology 6501-512
36
Effect of rivastigmine on delay to Dx of AD
results

• 202 Ss ? dementia (197 AD)
• Progression rate 17.3 vs 21.4
• Mean time to progression 3.6 vs 3.5 yrs
• Neuropsychological test n.s.
• MRI changes n.s. at year 3, 4 and study endpoint
• Post-hoc
• APOE e4 carriers between Rx n.s.
• But APOE e4 predictor for progression to AD

Feldman et al (2007) Lancet Neurology 6501-512
37
Time to progression to AD
Feldman et al (2007).Lancet Neurol.6501-512
38
AEs and safety of rivastigmine
Feldman et al (2007)
39
Meta-analysis ChEIs
Raschetti et al PLoS 20074e338
40
90 days DB RCT of Memantine for AAMI1

• N 60 AAMI (aged 50-79 years)
• 20mg memantine vs placebo for 90 days
• Several computerized cognitive tests as outcome
  measure
• Primary effects seem to be on attention and
  information processing speed, rather than on
  memory

1 Ferris et al (2007). Int J Geriatr Psychiatry
22448-453
41
MCI to treat or not to treat

• Gauthier S, Touchon J (2005) Mild cognitive
  impairment is not a clinical entity and should
  not be treated. Arch Neurol 62 11641166.
• Petersen RC, Morris JC (2005) Mild cognitive
  impairment as a clinical entity and treatment
  target. Arch Neurol 62 11601163.
• Kirshner HS (2005) Mild cognitive impairment to
  treat or not to treat. Curr Neurol Neurosci Rep
  5 455457.
• Moynihan R, Heath I, Henry D (2002) Selling
  sickness the pharmaceutical industry and disease
  mongering. BMJ 324 886890.

42
Can Rofecoxib delay progression to AD in MCI
patients?1

• N 1457 MCI pts (65)
• 25 mg rofecoxib vs placebo daily for 4 yrs
• Outcomes of converters, ADAS-Cog, CDR
• Results
• Progression rate to AD 6.4 (rofecoxib) vs 4.5
  (placebo)
• No differences on ADAS-Cog or CDR

1 Thal et al (2005). Neuropsychopharmacology
301204-1215
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Ginkgo biloba for prevention of cog decline

• 42-mths RCT of Ginkgo biloba
• 118 cog intact Ss (CDR 0)
• GBE n60
• Placebo n58
• Main outcome
• Progression to CDR 0.5
• Decline in episodic memory

Dodge et al (2008). Neurology.701809-1817
44
Ginkgo biloba for prevention of cog decline
results

• 21Ss ? CDR0.5 (7 Ginkgo biloba Extract)
• Progression to CDR 0.5
• Decline in episodic memory
• Post-hoc analysis (adjusted for med adherence)
• risk of progression
• Decline in episodic memory

n.s. (log-rank p0.06)
n.s. (p0.05)
GBE lt placebo (HR0.33)
GBE lt placebo
Dodge et al (2008). Neurology.701809-1817
45
Progression from CDR0 to CDR0.5
Ginkgo
Placebo
from Dodge et al (2008). Neurology. 701809-1817
46
Ginkgo Evaluation of Memory (GEM) study
cognitively intact and MCI

• 5-yr DB RCT of Ginkgo biloba
• 120mg BID
• Primary outcome
• Incidence of all-cause dementia
• Secondary outcomes
• Cognitive functional decline

DeKosky et al (2006). Contemp Clin
Trials.27238-253
47
Improving cognition in pre-dementia

• 24-wk RCT Ginkgo biloba1
• 12-wk RCT phosphatidylserine (a phospholipid)2
• 6-month CBT vs no-treatment3

• ? All showed no benefit on cognition
• A dopamine agonist (piribidel) did improve MMSE
  score over 90-days RCT 4

1van Dongen et al, 2000 2Jorisse et al, 2001 3
Rapp et al, 2002 4 Nagaraja et al, 2001
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Nutrition

• To prevent progression to MCI
• None to prevent progression of MCI

50
Dietary supplementations under investigation for
MCI
Completed studies
Ongoing studies (e.g.)

• Omega3-poly-unsaturated fatty acids (DHA, EPA)
• Vitamin B12 folic acid

• Curcumin bioperine
• Indian Curry Spice
• Black pepper
• Fish oil vs sunflower oil

• Cerefolin NAC
• Metylcobalamin
• L-methylfolate
• N-acetylcystein

From www.clinicaltrials.gov
51
Folic acid and dementia risk reduction1

• 3 yr RCT folic acid vs. placebo
• 818 healthy Ss (50-70yrs)
• Serum folate ?by 576
• Total homocysteine ? by 26
• Change in memory, information processing speed
  and sensorimotor speed
• folic acid group sig better than placebo

1Durga et al (2007). Lancet 369208-216
52
Effect of homocysteine lowering on cognitive
performance1

• 2 yr DB RCT
• N 276 healthy Ss (aged 65)
• 1000mg folate 500mg Vitamin B12 10mg B6
• Results
• Homocysteine levels Vitamin lt placebo
• Cognitive performance n.s.

1 McMahon et al (2006). N Engl J Med
354(26)2764-2772
53
Mediterranean diet for prevention of dementia1

• N 2258 Ss without dementia
• 4 yrs of follow-up
• ? 262 incidents of AD
• Higher adherence to diet ? risk ? (HR 0.91)
• Compared to lowest adherence group
• Middle tertile HR 0.85
• Highest tertile HR 0.60

1 Scarmeas et al (2006). Ann Neurol 59912-921
54
Behavioural therapies under investigation for MCI
Completed studies
Ongoing studies (e.g.)

• Social walking vs resources activities for life
  long independence
• MEMO programme

• Support groups
• Aerobic exercise
• Computer-based Training

• Recollection T.
• Complex cog T.
• Computerized cog training
• Aerobic exercise vs stretching toning

From www.clinicaltrials.gov
55
Cognitive intervention for MCI
56
Cognitive interventions - to prevent MCI
developing - to prevent MCI progressing to
dementia
57
Cognitive training for older adults1

• RCT of N 2832 aged 65-94 years
• Randomised to 10 sessions of group training for
  memory, reasoning, speed of processing or
  no-contact
• 60 randomly received 4-session booster after 11
  months
• Interventions ? the targeted cognitive ability
• Booster ? training gains in speed reasoning at
  2 year follow-up

1Ball et al JAMA 20022882271-81
58
Cognitive intervention for improving episodic
memory in MCI

• Training of episodic memory strategies (8x120min)
• 47 Ss (28 MCI, 17 non-impaired (NI) )
• Intervention vs waiting-list group
• Pre-/Post assessments
• Primary outcome measures
• List recall
• Face-name association
• Text memory

Belleville et al (2006).Dement Geriatr Cogn
Disord 22486-499
59
Cognitive intervention for improving episodic
memory in MCI

• Training of episodic memory strategies (8x120min)
• 47 Ss (28 MCI, 17 non-impaired (NI) )
• Intervention vs waiting-list group
• Pre-/Post assessments
• Primary outcome measures
• List recall ? for MCI and NI
• Face-name association ? for MCI and NI
• Text memory

Belleville et al (2006).Dement Geriatr Cogn
Disord 22486-499
60
Computer-based cog training for AD, MCI and
Multiple System Atrophy

• Two computer-based training programs (TNP)
• 10 AD vs 10 MCI vs 10 MSA
• Results after 3 months
• AD ? on MMSE, verbal production, executive
  function
• MCI ? on behavioural memory
• MSA no improvement

Cipriani et al (2006).Arch of Gerontology and
Geriatrics 43327-335
61
Computer-based training in addition to ChEIs in
MCI pts

• 1-yr RCT of
• ChEIs neuropsychological training TNP (n15)
• ChEIs (n22) vs No treatment (n22)
• TNP 3 x 20 sessions á 1hr
• Primary outcome change from baseline to FU on
  neuropsych testing
• Secondary outcome NPI and GDS

Rozzini et al (2007) Int J Geriatr Psychiatry
22356-360
62
Significant changes from baseline to 1-yr
63
Brain reserve and cognitive decline

• Non-parametric systematic review of literature
• Aim systematic integration of independent
  cohort studies of cog change to clarify
  relationship with behavioural brain reserve

Valenzuela Sachdev (2006).Psychol Med
361065-1073
64
Brain reserve and cognitive decline

• 18 studies included
• Education 13 studies
• Occupation 4 studies
• Mental activities 6 studies
• Overall 39 outcomes from 18 studies
• N 47,000 persons

Valenzuela Sachdev (2006).Psychol Med
361065-1073
65
Effect of education on cog decline
large and significant
of studies
Effect size
Valenzuela Sachdev (2006) Psychol Med
361065-1073
66
Effect of occupation on cog decline
n.s.
Valenzuela Sachdev (2006) Psychol Med
361065-1073
67
Effect of complex mental activities
moderate and significant
Valenzuela Sachdev (2006) Psychol Med
361065-1073
68
Overall effect of brain reserve
large and significant
Valenzuela Sachdev (2006) Psychol Med
361065-1073
69
Review of cog interventions for MCI 1

• 2 non-randomized and 2 RCTs on the effects of
  cognitive training
• Results
• ? depression and ?cognition2
• ? subjective memory and long-term maintenance3
• long-term ? on cognition4
• gt memory improvement 5

1Massoud et al (2007).Alzheimers
dementia3283-291 2Olazaran et al (2004).
Neurology 632348-53 3Rapp et al (2002). Aging
Ment Health.65-11 4Guenther et al (2003).
5Belleville et al (2006).
70
Summary of cog interventions for MCI1

• Evidence of benefit, but need
• Replication studies
• Proper RCT-designs
• Lager sample sizes
• Analyses controlling for type 1 errors

1Massoud et al (2007) Alzheimers
dementia3283-291
71
Review of RCTs of cognitive training in healthy
older people

• Systematic review of RCTs with longitudinal FU
  (gt3mths)
• 7 RCTs met inclusion criteria
• Strong ES for cog exercise intervention vs
  wait-and-see controls
• Longer FU duration (gt2yrs) ? ES no lower
• Quality of trials generally low

Valenzuela Sachdev (2008). Am J Geriatr
Psychiatry (in press)
72
Review of RCTs of cognitive training in healthy
elderly
Valenzuela Sachdev (2008). Am J Geriatr
Psychiatry (in press)
73
Physical interventions for MCI
74
Effect of physical activity on cog function in
healthy people aged 50

• 24-wk RCT
• Follow-up 18 months
• physical activity (walking) vs education usual
  care
• 138 Ss completed study
• Main outcome measure
• Change in ADAS-cog over 18mths

Lautenschlager et al (2008).JAMA 300(9)1027-1037
75
Effect on ADAS-Cog 1
decline
improvement
1 Lautenschlager et al (2008). JAMA,
300(9)1027-1037
76
Effect on delayed recall of word list1
improvement
decline
1 Lautenschlager et al (2008). JAMA,
300(9)1027-1037
77
Effect on CDR SB1
decline
improvement
1 Lautenschlager et al (2008). JAMA,
300(9)1027-1037
78
Effect on total steps per week 1
increase
decrease
1 Lautenschlager et al (2008). JAMA,
300(9)1027-1037
79
Physical activity and executive functions in MCI

• 6-wk RCT
• walking vs hand/face exercises vs controls
• Intervention 30min/day, 3days/wk, 6 weeks
• Main outcome measure
• ? in general (GF) executive functions (EF)

• Both interventions (nearly) sig ? EF

Scherder et al (2005).Aging Mental Health
9(3)272-280
80
Design of a 1-yr RCT on effects of walking and
vitamin supplementation in MCI

• Walking program (WP)
• Cardiovascular endurance?
• 2 x 1hr/week
• Duration 1 yr
• Placebo activity program (PAP) eg stretching

• Vitamin supplementation
• 50 mg B6
• 5 mg folic acid
• 0.4 mg B12
• Duration 1 yr
• Placebo
• Identically looking pill

Van Uffelen et al (2005) BMC Geriatrics 518
81
Design of a 1-yr RCT on effects of walking and
vitamin supplementation in MCI

• 4 groups
• WP Vit
• WP placebo
• PAP Vit
• PAP placebo

• Main outcome measure Cognitive function
• Secondary outcome measures
• Psycholog. wellbeing
• Physical activity
• Cardiovasc. endurance
• Blood vitamin levels

Van Uffelen et al (2005).BMC Geriatrics 518
82
Results of walking vs vitamin B

• N152 Ss
• No main intervention effect found for either
  intervention
• Post hoc those with better adherence to WP
• Women sig ? of attention memory with each ? in
  session attendance
• Men (attendance at least 75) Memory ?

Van Uffelen et al (2008). Br J Sports Med
42344-351
83
Leisure activities and risk of aMCI

• Prospective cohort study of 437 Ss 75
• Follow-up median 5.6 yrs
• Outcomes - Influence of leisure activity on risk
  of development of aMCI?
• Cognitive (CAS) physical activities score (PAS)
• Results 58 ? aMCI
• 1 point ? in CAS BUT NOT PAS ? ?risk

Verghese et al (2006) Neurology 66821-827
84
Leisure activities and risk of aMCI
From Verghese et al (2006). Neurology 66821-827
85
Physical activity and white matter lesion
progression

• Association between physical activity and WMLs
• 179 Ss followed for 5 yrs (median)
• 59 AD incident cases
• 60 MCI incident cases
• 60 cognitive stable
• Physical activity was NOT sig associated with ?
  of periventricular or deep WMLs progression

Podewils et al (2007) Neurology 681223-1226
86
Exercise interventions for dementia and CI

• Series of evidence-based interventions ? Seattle
  Protocols
• Based on social learning gerontology theories
• Include regular physical exercise as well as
  education to set and maintain realistic exercise
  goals
• RALLI (Resources and Activities for Life Long
  Independence) intervention to promote exercise
  in individuals with MCI

Teri et al (2008) J Nutr Health Aging
12(6)391-394
87
Results from a RALLI-pilot study

• 34 Ss
• 6 months follow-up, to date only 12-wk data
  available

Teri et al (2008) J Nutr Health Aging
12(6)391-394
88
Effects of fitness interventions on cognition1
lt30 no benefit strength aerobic gt aerobic
alone Long term best
1Colcombe Kramer (2003) Psychol Sci. 14
125-130
89
Effects of exercise on cardiovascular fitness1
1Heyn et al (2004). Arch Phys Med Rehabil. 85
1694-1704
90
Effects of exercise on physical strength1
1Heyn et al (2004). Arch Phys Med Rehabil. 85
1694-1704
91
Effects of exercise on flexibility and BMI
outcomes1
flexibility
BMI
1Heyn et al (2004). Arch Phys Med Rehabil. 85
1694-1704
92
Prevention of MCI
93
Components of an Active Lifestyle which may
prevent cog decline in MCI
Troyer et al (2007).Geriatrics Aging
10(7)444-448
94
Preventing Pre-dementia syndrome

• Higher education protective for MCI1
• Exercise social activity programs
• exercise protective for CIND in women2
• decreased risk with increased level of physical
  exercise2
• HRT
• estrogen plus progestin shown not to prevent MCI
  in postmenopausal women3

1Tervo et al, 2004 2Laurin et al, 2001
3Shumaker et al, 2003
95
Other Potential Interventions

• Vaccine?
• Nerve-growth factor?
• Statins?
• Other antioxidants?
• Anti-inflammatories?
• Nutrition? Regular alcohol? Fish?
• Education?

96
Apoe4 and MCI

• ApoEe4 frequency
• controls lt ARMD ? AD1
• ? 40 MCI patients carried at least 1 Apoe4
  allele2
• However,
• Other studies show no difference in Apoe4 status
  between MCI and controls2
• Non-carriers can still develop MCI3

1Blesa et al, 1996 2Farlow et al, 2004 3Collie
et al, 2002 4Anttila et al, 2004
97
General interventions

• Advice note possible improvement
• Driving
• Employment
• Legal ePOA, eGship

• Finances
• Monitor cognition, function, mood depression,
  anxiety
• Family counselling

98
Does it help to make MCI diagnosis?

• Currently no efficient drug treatment available
• If, only for high-risk pts (e.g. ApoE4 carriers)
• Cognitive training and physical exercise might be
  beneficial
• Some pts with MCI recover
• Might help to delay progression to dementia in
  those who actually progress

99
MCI coping with an uncertain label 1

• Qualitatively interview study with 8 MCI pts
• How do MCI patients cope with Dx?
• Derive key themes for prospective MCI
  support-groups
• Results four common themes found

Changes in various areas
Attributions (eg normal, trait, dementia etc)
Consequences for pts families (eg sadness,
anger, burden)
Coping Strategies (emotion-, problem-,
avoidance- focused)
1 Joosten-Weyn et al (2008). Int J Geriatr
Psychiatry 23148-154
100
Keypoints from Joosten-Weyn et al1

• MCI patients encounter stress-inducing
  difficulties in social, psychological and
  everyday functioning
• MCI patients have numerous, concurrent
  attributions that may induce depressive mood or
  anxiety
• MCI patients need specific information in order
  to cope with MCI label

1 Joosten-Weyn et al (2008). Int J Geriatr
Psychiatry 23148-154
101
Conclusions

• Diagnosis of MCI is slippery
• No definitive drug treatment for MCI
• Cognitive and physical exercise beneficial
• Cardiovascular risk factors BP, weight,
  cholesterol, smoking
• Regular follow-up

102
Thank you

• h.brodaty_at_unsw.edu.au
• www.dementia.unsw.edu.au