BMI Predicts Alzheimer's in Amnestic MCI: 3-Year Study

1. Low BMI predicts incident Alzheimer’s disease in older adults with amnestic mild cognitive impairment A 3-year prospective cohort study (Chu LW, Yik PY, Kwan F, Chan CSY , Song YQ) Prof. Leung-Wing ChuMD, FRCP (Lond., 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 • OC 27

2. Conflict of Interest • All authors • Chu LW, Yik PY, Kwan F, Chan CSY , Song YQ • Has no real or apparent conflicts of interest to report

3. 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)

4. 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

5. Progression of MCI • Progression of aMCI to dementia 12% per year; 80%/6 years (Petersen, 1999 & 2001) • Neuropsych. Tests, particularly delayed recall memory test, APOE4 Predictors of progression (Petersen 1999, Fleisher 2006) • Other predictors: Imaging (MRI, PET), csf biomarkers

6. BMI -Predictor of progressionfrom amnestic Mild Cognitive Impairment (aMCI) to AD What about clinical parameter like BMI as predictor? • Weight loss associated with subsequent development of Alzheimer’s disease (AD). • But, Body Mass Index (BMI) as a predictor has not been studied fully • Our previous cross-sectional study • lower BMI in AD& aMCI than cognitively normal older adults (Chu et al, 2009)

7. Objectives of the study The objective of the present prospective study was • to investigate BMI as a predictor of progression from aMCI to AD in older adults in a 3-year cohort study among Chinese older adults (Southern Chinese)

8. Methods • Design:A 3-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 tests including MMSE, ADAS-cog • neuropsychological tests, and • apolipoprotein E genotype (APOE)

9. 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)

10. Methods • Follow-up: All subjects were followed up for three years • Outcome: • Dementia by DSM-IV criteria & • AD was diagnosed by the NINCDS- ADRDA criteria for probable AD

11. Results • 139 Chinese older adults with aMCI were recruited. • Females = 75.5% • Mean age =75.4 (SD 6.6) years • Mean MMSE score = 23.4 (SD 3.9) • Mean ADAS-cog score = 14.29 (SD 5.58) • Mean BMI =23.6 (SD 3.6) Kg/m2

12. Results • 3-year follow-up, 25.2% (n=35)* developed dementia (by DSM-IV criteria) • All having Alzheimer’s disease (by NINCDS-ADRDA criteria) *versus 0.6% (n= 359) over 3-year follow-up in another cohort of cognitively normal Chinese older adults in HK

13. Bivariate analyses of predictors of aMCI progression to AD Bivariate analyses showed that advanced age, low body mass index (BMI), and ischemic heart disease (IHD) increased the risk of progression to AD significantly Waist-Hip ratio (WHR) only showed a non-significant trends Non-significant Gender, education, Comorbid diseases - hypertension, DM, previous stroke, COPD, osteoporosis, depression and APOE4+ (1 or 2 copies)

14. Bivariate analyses of predictors (Co-morbid ds., genetic)

15. Bivariate analyses of predictors (Cognitive, neuropsychological tests) (Most cognitive, neuropsychological tests p<0.05)

16. Bivariate analyses of predictors (Demographic, co-morbid ds.) Note: Mean ± SD, or %; IHD=ischemic heart ds

17. Logistic regression analysis:BMI –an independent predictorof progression to AD • In multivariate logistic analyses, • BMI and ischemic heart disease (IHD) were independent predictors of progression to AD. • BMI reduced the risk (RR=0.88, 95% CI 0.77, 0.99) , and • IHD increased the risk (RR =3.17, 95% CI 1.01, 9.13) • after adjustment for age, gender and apolipoprotein E genotype (Age but not apolipoprotein E genotype also increased the risk.)

18. Bivariate analyses of predictor BMI (in quartiles) X2 statistics

19. Logistic regression analysis:Quartiles of BMI – independent predictor • Lowest BMI was an independent predictor of aMCI progression to AD. • Lowest BMI increased the risk (RR=3.55, 95% CI 1.04,12.2) , and • IHD showed a trend towards an increased risk (RR =3.15, 95% CI 0.98, 10.13) • after adjustment for age, gender and apolipoprotein E genotype (Age but not apolipoprotein E genotype also increased the risk.)

20. Logistic regression analysis:Quartiles of BMI – independent predictor Note: adjusted for age, gender and apolipoprotein E genotype

21. Discussion • Meta-analyses ofprevious studies • Mid-life BMI: Both • low BMI and high BMI increased the risk of dementia and AD • Does late-life BMI predict AD in general older adults in cohort studies? • OverallN.S. • Obese vs. non-obese (2 studies): Pooled RR 1.46 (95% CI 0.97-2.21) • Risk of AD by BMI (continuous) (8 studies) ): Pooled RR 0.97 (95% CI 0.92-1.02) • Limitation-Inadequate no. of studies (n=8) *Anstey et al, 2011

22. Discussion • How about late-life BMI in MCI  AD? • Very inadequate research • Only one previous study on BMI and cognitive decline • Lower BMI predicts decline in cognitive performance (MMSE, ADAS-cog) at 1-year follow-up but • progression to dementia/ AD N.S. (Cronk et al, 2010)

23. Discussion • To our knowledge, this is the 1st study that found • 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 12% over 3 years of follow-up • aMCI subjects with the lowest quartile of BMI (vs high quartile) has 3.6 times the risk of progression to AD

24. Discussion • In our previous cross-sectional study on 3 groups of older adults • Significant progressive decline in BMI from NaMCIAD (Chu LW et al JAD, 2009) • Low BMI is likely a preclinical symptom/sign of aMCI conversion to AD

25. Conclusion • In older adults, low BMI predicts an increased risk of AD development after 3 years follow-up. • Low BMI represents a preclinical somatic sign of pre-AD in older adults with aMCI

26. Acknowledgement Co-investigators: Song YQ 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

27. Thank you