1. Clinical, cognitive and genetic predictors of conversion from amnestic mild cognitive impairment to Alzheimer’s disease in Chinese older adults
(Chu LW, Mok W, Chung CP, Chan M, Yik PY, Kwan F, Chan CSY , Song YQ, Lee P)
Prof. Leung-Wing Chu MD, FRCP (Edin. & Glas.), FHKCP, FHKAM (Medicine)
Honorary Clinical Professor, and Associate Director, Centre on Ageing, and
Chairman, HKU AD Research Network, SRT Healthy Ageing,
The University of Hong Kong
Chief, Division of Geriatrics, Queen Mary Hospital
*OC126
March 29, 2011

2. Conflict of Interest All authors
Chu LW, Mok W, Chung CP, Chan M, Yik PY, Kwan F, Chan CSY , Song YQ, Lee P
Has no real or apparent conflicts of interest to report
*ADI
OC126

3. Prevalence of AD in Chinese (Systematic analysis of 1980-2004 25 studies in China*)
Lower
Prevalence In
Men %
*Dong et al, 2007 4

4. Prevalence of Very Mild & Mild Dementia in Hong Kong
Older people 60+
Prevalence of dementia =11.4%
Very mild (CDR 0.5) = 5.8%
Mild (CDR 1.0) = 5.4
Subtypes
73.5% possible AD
22.4% possible VaD
3.9% PD dementia or LBD
(Lam L et al, 2008) 4

5. Delay in Diagnosis in AD Symptom onset and 1st consultation
Mean Delay years in AD patients1
Symptoms ignored as “normal ageing!”
1Chiu KC et al, 2002
(More than 2 times that of Caucasian AD patients (i.e. 1.2 years in Caucasian dementia patients2 ). 2Cattel C et al, J Gerontol: Med Sci 2000; M98)

6. Undiagnosed Dementia in the HK Community
Prevalence of previously diagnosed dementia
1.7% (including old age homes)1
0.33% (excluding old age homes) 2
Undiagnosed dementia: Estimated prevalence – 9.7% to 11.1%
1Chu LW et al, 1998; 2Chu LW et al, 2005

7. Mild cognitive Impairment (MCI)
Mild cognitive impairment (MCI) is a clinical syndrome defined as
cognitive decline greater than that expected for a person’s age and education level
but does not affect notably with activities of daily life (Gauthier S et al, Lancet 2006)
MCI refers to
a transitional cognitive phase between cognition of normal aging and mild dementia &
may precede the onset of dementia or AD (Petersen et al, 1999 & 2001)

8. MCI Subtypes Amnestic MCI (aMCI)
1. MCI (Amnestic) (Single memory domain)
Alzheimer’s disease (AD)
2. MCI (Multiple domains slightly impaired)
 Alzheimer’s disease; Vascular Dementia
Non-amnestic MCI (naMCI)
3. MCI (Single Non-memory Domain)
 Fronto temporal Dementia; Lewy Body Dementia; Vascular Dementia; Primary Progressive Aphasia; Parkinson’s Disease; Alzheimer's Disease

9. Progression of MCI Conversion rate and Predictors
Progression of aMCI to dementia 12% per year; 80%/6 years (Petersen, 1999 & 2001)
Clinical, neuropsychological, genetic predictors of conversion or progression to dementia / AD
Neuropsych. Tests, particularly delayed recall memory test, APOE4 (Petersen 1999, Fleisher 2006)
Other predictors: Imaging (MRI, PET), csf biomarkers

10. Predictors of amnestic Mild Cognitive Impairment (aMCI) conversion to dementia
Clinical predictor: Body Mass Index (BMI) as a predictor has not been studied fully
Non-demented older adults –low BMI predicts dementia/AD in several studies
MCI: Low BMI  more cognitive decline but not dementia conversion in 1 study (Cronk et al, 2010)
Limited Chinese data on MCI on
The clinical, genetic & cognitive predictors of conversion of MCI to dementia,
Wang et al, 58 MCI subjects 32.7% AD over 3 years
Only cognitive performance independent predictor (APOE & hippocampal volume – NS)

11. Objectives of the study
To investigate the conversion rate of aMCI to AD/dementia in aMCI in Chinese older adults (Southern Chinese)
To investigate the clinical, genetic & cognitive predictors of conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease (AD)
Particularly, to study if BMI predicts conversion of aMCI to AD*
in Chinese older adults (Southern Chinese)
*In our previous cross-sectional study, AD & aMCI lower BMI than cognitively normal older adults

12. Methods Design: A one-year cohort study Setting: Ambulatory setting
Subjects: Chinese older adults, aged 55 to 93 years old, with aMCI criteria modified from the Petersen’s criteria.
Measurements:
Baseline demographic,
BMI,
co-morbid diseases,
cognitive including MMSE, ADAS-cog
neuropsychological tests, and
apolipoprotein E genotype (APOE)

13. aMCI criteria- Modified from Petersen et al (1999)
the presence of memory complaint (corroborated by an informant),
impaired memory function for age and education (< 1SD verbal memory recall test)*
intact activities of daily living and
no dementia (by DSM-IV criteria)
*Note: 1SD better Sens. & spec. than 1.5 SD in predicting dementia (Busse A et al, 2006)
(delayed word recall score < 1 SD below normal age-and education-matched mean for Chinese older adults)

14. Methods Follow-up: All subjects were followed up for one year.
Outcome:
Dementia by DSM-IV criteria &
AD was diagnosed by the NINCDS- ADRDA criteria for probable AD

15. Results
243 Chinese older adults with aMCI were recruited from Jan to Nov. 2009
One year follow-up, 16.5% (n=40) developed dementia (by DSM-IV criteria)*
All having Alzheimer’s disease (by NINCDS-ADRDA criteria)
*versus 0.5% (2 out of 444) in another cohort of
cognitively normal Chinese older adults in HK

16. Bivariate analyses of predictors of aMCI conversion to AD
Bivariate analyses showed that
advanced age, low body mass index (BMI), APOE4+ (1 or 2 copies), low MMSE, DWRT, ADAS-cog and neuropsychological assessment tests’ scores increased the risk of conversion to AD significantly
Arthritis & CHD showed only non-significant trends

17. Bivariate analyses of predictors of aMCI conversion to AD (Demographic, co-morbid ds.)
at baseline
Convert to AD
(n = 40)
Stable
(n = 203) p
Sex (F),%)
60.0
72.4
0.116
Age, yrs.
77.38 ± 5.61
74.90 ± 6.44
0.024
Education level, yrs
3.10 ± 4.06
2.83 ± 7.05
0.695
BMI, Kg/m2
22.26 ± 3.18
24.23 ± 3.57
0.001
Arthritis
7.5
20.3
0.055
CHD
20.0
10.4
0.087
Note: Mean ± SD, or %; CHD=coro heart ds

18. Bivariate analyses of predictors of aMCI conversion to AD (Co-morbid ds., genetic)
at baseline
Convert to AD
(n = 40)
Stable
(n = 203) p HT
55.0
58.4
0.689 DM
22.5
26.7
0.577
Depression
(treated)
5.0
0.989
Hyperlipidemia
70.0
62.4
0.360
APOE4+ (versus 4-)
35.0
15.5
0.004
Note: %

19. Bivariate analyses of predictors of aMCI conversion to AD (Cognitive, neuropsychological tests)
at baseline (Mean ± SD)
Convert to AD
(n = 40)
Stable
(n = 203) p
MMSE
21.90 ± 4.04
23.52 ± 3.59
0.011
ADAS-cog
16.52 ± 5.47
14.49 ± 5.52
0.035
DWRT,10-word
1.10 ± 1.08
2.33 ± 1.70
<0.001
Selective Reminding Test
30-min recall
0.60 ± 1.43
2.51 ± 2.62
Visual reproduction-delayed recall
1.23 ± 2.46
6.47 ± 7.53
(Most cognitive, neuropsychological tests p<0.05)

20. Logistic regression analyses: Independent predictors of aMCI conversion to AD
Relative Risk (RR)
95% CI RR p
APOE4+ (vs. 4-)
2.70
1.13 – 6.48
0.026
BMI, Kg/m2
0.84
0.75 – 0.95
0.004
SRT-30
0.75
0.58 – 0.97
0.027
VR-Delayed Recall
0.79
0.67 – 0.93

21. Logistic regression analyses: Independent predictors of aMCI conversion to AD
After adjustment for confounders, logistic regression analyses showed that
APOE4+ (vs. 4-) (RR=2.70),
BMI (RR=0.84),
Verbal memory test: 30-minute recall of the selective reminding test (RR=0.75)
Visual memory test: delayed recall score in visual reproduction test (RR=0.79), and
were significant independent predictors for conversion to AD.
Age, arthritis, CHD were non-significant &
MMSE, DWRT, ADAS-cog were not independent predictors because of SRT-30 & VR-delayed w

22. Discussion Similar to previous studies, we found
APOE4, low cognitive / neurpsych memory test predicts conversion of aMCI to dementia/AD in (Southern) Chinese older adults (with aMCI )
However, to our knowledge, this is the 1st study
BMI predicts future risk of aMCI to dementia/AD
Low BMI increases the risk
One kg/m2 less in BMI increases the risk of aMCI to dementia (AD) by 16%

23. Discussion
In our previous cross-sectional study on 3 groups of older adults
Significant progressive decline in BMI reported from NaMCIAD
(Chu LW et al JAD, 2009)
Low BMI can either be a risk factor or preclinical symptom/sign of aMCI conversion to AD
Cognitively normal
24.6 ± 4.2 Kg/m2
aMCI
23.9 ± 3.6 Kg/m2 AD
22.9 ± 3.7 Kg/m2

24. Conclusions In Chinese older adults,
low BMI, as well as
the presence of apolipoprotein epsilon 4, and
poor performance in delayed recall tests in verbal and visual memory tests
predict increased risks of aMCI conversion to AD in this 1-year cohort study.
Future studies needed.

25. Acknowledgement
Co-investigators: Mok W, Chung CP, Chan M, Song YQ, Lee P
Research staff:
Yik PY, Kwan F, Chan CSY
Research grant support:
SK Yee Medical Foundation, Hong Kong
SRT Healthy Aging, the University of Hong Kong:
Alzheimer’s Disease Research Network

26. Thank you