Singapore Longitudinal Ageing Studies (SLAS):

Tze Pin Ng (MD), Gerontology Research Programme, National University Health System/ Yong Loo Lin School of Medicine, National

University of Singapore

ILSI Conference on Healthy Aging in Asia, March 4-5, 2013 Singapore

Psychosocial, lifestyle, behavioral, biomedical determinants of

ageing and health outcomes

Acknowledgements

Grant funding support

A*STAR Biomedical Research Council

• 03/1/21/17/214: Gerontology Research Programme : Biological, Clinical, Psychosocial And Behavourial Predictors Of

Health Status In Prospectively Followed-Up Cohorts Of Elderly Persons

• SIgN 10-036: Immune Signatures and Biomarker Profiling of Frailty

Ministry of Health National Medical Research Council

• NMRC/0846/2004: Randomised Controlled Trial Of A Community-Based Early Psychiatric Intervention Strategy To Screen

And Manage Depression In The Elderly

• NMRC/1108/2007: Randomized Controlled Trial of Community-based Nutritional, Physical and Cognitive Training

Intervention Programmes for At Risk Frail Elderly

• NMRC/08/1/21/19/567: Gerontology Research Programme: Nutritional, cardiometabolic and vascular factors, ApoE4

gene interactions, and dementia and depression risk”

• CIRG12may033: Insulin Resistance and Mild Cognitive Impairment (MCI) in Older Adults with Pre-Diabetes and Diabetes:

Cognitive Effects of Lifestyle Intervention and Metformin Treatment in a Randomized Controlled Trial

• HSRG0016/2010 : Consultation Liaison and Integrated Care for COPD patients with Psychiatric Co-Morbidity

National University Health System, National University of Singapore,

• AIRC R-177-000-031-133: The built environment and quality of life of older persons

• NUHSRO/2011/009/STB/B2B-05: Levels and activities of sirtuins in peripheral blood cells as biomarkers for healthy

ageing and ageing disorders

Venerable Yen Pei-National Kidney Foundation Research Fund

• NKFRC/2010/07/16Mood,cognitive, physical functioning and quality of life in older adults with chronic kidney disease

Alice Lim Memorial Fund

• R-177-000-030-290: The Association between diet & health status in Asian Elderly

Anonymous Donor

R-177-000-028-720. Successful Ageing: Characterizing its Multiple Dimensions in Singaporean Seniors and the

Development and Validation of a Measurement Scale for Health Care and Promotion Programmes.

GRP-SLAS Collaborators

A/Prof Ng Tze Pin (PI)

A/Prof Yap Keng Bee

A/Prof Lee Tih Shih

A/P Lim Su Chi

A/Prof Fong Ngan Phoon

Prof Kua Ee Heok

A/Prof Tan Chay Hoon

Dr Tong Yoke Yin Terry

Dr Yap Lin Kiat Philip

Dr Tan Boon Yeow

Dr Chong Mei Siang

Dr Lim Wee Shiong

Dr Feng Lei

Dr Simon Lowes Collinson

Dr Anis Larbi

A/P Tang Bor Luen

Prof Bengt Winblad

Prof Laura Fratigliori

Research Fellows and

Graduate Students

Dr Feng Liang

Dr Shwe Zin Nyunt

Ms Hin-Hiang Susan

Ms Lim May Li

Dr Gao Qi

Dr Khin Chaw Yu Aung

Ms Gwee Xinyi

Dr Jiang Mingjun

Research Staff Ms Catherine Yeong

Ms Clare Chan

Ms Dorothy Teo

Ms Hamidah Abd Kadir

Ms Irene Neo

Ms Lim Bee Neo

Ms Low Yin Fong

Ms Rosalind Goh

Ms Teresa Kwan

Ms Wang Wah Fong

Voluntary Welfare Organizations

Support

Geylang East Home for the Aged,

Presbyterian Community Services,

Thye Hua Kwan Moral Society

(Moral Neighbourhood Links),

Yuhua Neighbourhood Link,

Henderson Senior Citizens’ Home,

NTUC Eldercare Co-op Ltd,

Thong Kheng Seniors Activity

Centre (Queenstown Centre)

Redhill Moral Seniors Activity

Centre.

Singapore Longitudinal Ageing Studies

Population-based prospective cohort study of ageing and

health of Singaporean older adults

To investigate psychosocial, lifestyle, behavioral, biomedical

and healthcare determinants of ageing and age-related

health outcomes

To generate research information to promote healthy ageing

and guide clinical practices in care of the aged

SLAS-1: N=2808

South East Region

SLAS-2: N=3,200

South Central Region

South West Region

Community-living older adults age 55+

Singapore Longitudinal Ageing Studies (2004 – 2013)

Domains Measurements

Psychosocial Biodata, social network & support, work and retirement

Lifestyle and

behavior

Lifestyle and behaviour: smoking, alcohol, coffee, tea, curry, mobile phone, computer use, Leisure-time

activities,

Medical,

biological,

physiological

Medical history, medications, adherence, supplements, health service use (doctor visits, hospitalization)

BP, ECG, COPD Questionnaire, BORG dyspnea scale, Spirometry (pre- and post-bronchodilator), Logmar,

Retinal Photography

Blood: fasting glucose, lipids, homocysteine, haematological, eGFR, albumin, hsCRP, TNF-a, IL-6

Diet and

nutrition

Nutrition screening (modified NSI), food frequency intake, 24-hour food record, serum Hb, albumin,

homocysteine, folate, B12,

Physical

function

Instrumental and basic ADL, Handgrip, knee extension strength, POMA-Balance, POMA-Gait, Repeated Chair

Rise, TUG, Fast Gait Speed Test; Total Energy Expenditure, LASA Physical Activity Questionnaire

Health status Quality of Life (SF-12, EQ5D), 4-item Life Satisfaction scale, Successful ageing

Psychological Geriatric Depression Scale (15 items), SCID diagnoses of psychiatric disorders; Sleep problems

Resilience, optimism, ageing perceptions, mortality salience

Neurocognitive

Subjective Memory and Cognitive Complaint, IQCODE, Mini Mental State Examination (MMSE), NPI, MOCA,

RBANS, Comprehensive Neurocognitive Test Battery: RAVLT, VR, Digit Span, CRT, SDMT, CTT, BD, BNT, story

recall), Clinical Dementia Rating (CDR), Hatchinski, panel consensus diagnosis of dementia

Stored DNA ,

PBMC, serum Genetic, inflammatory and immune and other ad hoc studies

Measurements Visit 1 Visit 2 Visit 3 Visit 4 Visit 5

Home Home Centre Cenre Cente

Psychosocial

Lifestyle and behaviour

Biomedical and physical function

Neurocognitive

Dementia assessment

Singapore Longitudinal Ageing Studies

SLAS-1

Baseline measurements: 2004-15

Follow up measurements: 2007-2008; 2010-2011

Mortality follow-up till 2010: mean 6 years

SLAS-2

Baseline measurements: 2009-2010

Follow-up measurements: 2012-ongoing

Cognition and Dementia

– Dementia prevalence

– Risk and Protective Factors

Depression

– Relationships with chronic diseases

– Health service use

– Community Screening and Treatment

Physical function

– Population trends and attributable risks

Frailty

– Defining and characterizing frailty-prefrail states

– Immune ageing factors

– Prevention trial of nutrition, physical and cognitive training

interventions

Successful ageing and quality of life

– Models of successful ageing

– Ethnic and cultural dimensions

– Work, Retirement and Living Alone

Summary of Findings

Dementia, Cognitive Impairment and Decline Prevalence, Risk and Protective Factors

Demographic Factors

Increasing age

Female gender

Low education

Malay and Indian ethnicity

Am J Geriatr Psychiatry. 2007

0

1

2

3

4

5

6

7

8

9

10

Non-depressed

Depressed

0

10

20

30

40

50

Non-depressed

Depressed

% with cognitive decline

Non-APOE-e4

carriers

APOE-e4

carriers

% with Incident Cognitive Impairment

J Am Ger Soc 2009; 57:1058–1063. Journal of Gerontology Series A Medical Sciences 2009

Women Men

Sex * Depression APOE-e4 * Depression

Depressive symptoms

Particularly in men and APOE-e4 carriers

Cogntive Impairment (MMSE<23)

Low BP Low BPNormal BP Normal BPHigh BP High BP0

2

4

6

8

10

12

14

16

18

20

Stable BP Unstable BP

Percent

Blood Pressure and Postural Hypotension

Dement Geriatr Cogn Disord 2008;26:239–246

Among participants free of cardiovascular disease and stroke

• Frequent leisure time

activities

• Productive activities > social > physical activities

• Association is exaggerated in APOE-e4 carriers

Int Psychogeriatr. 2008, Jan:1-15

0.6 0.62

1

0

0.2

0.4

0.6

0.8

1

1.2

Relative Risk of Cognitive Decline

Low Moderate High

Level of Leisure Time Activities

1 1

0.760.85

0.36

1

0

0.2

0.4

0.6

0.8

1

1.2

At least 1 Physical

Activities

At least 1 Social

Activities

At least 1 Productive

Activities

No Yes

Multivariate

Odds Ratio

1

0.65

0.37

0.68

0.36

1

0

0.2

0.4

0.6

0.8

1

1.2

Non-APOE-e4 Carriers APOE-e4 Carriers

Low Medium High

Active Lifestyle Relative Risk of Cognitive Decline

No Yes 0

0.5

1

1.5

Metabolic Syndrome

Cognitive Decline

Metabolic Syndrome

¶ Adjusted for age, gender, education, baseline

depressive symptoms (for whole sample), hypertension,

cardiovascular illness or stroke, other medical co-

morbidity, other anti-diabetic use, APOE-4 carrier status,

fasting blood glucose, BMI and duration of diabetes.

Amnestic MCI

Subgroups

Association between MetS and Amnestic MCI

OR(95%CI) P

APOE-e4 Carrier 3.35 (1.03-10.85) 0.044

Non-APOE-ε4 carrier 1.54 (0.94-2.50) 0.084

APOE-ε4 Carrier and Age≥65 2.82 (0.60-13.3) 0.19

APOE-ε4 Carrier and Age<65 6.57 (1.03-41.7) 0.046

Non-APOE-ε4 Carrier and Age≥65 1.60 (0.86-2.97) 0.14

Non-APOE-ε4 Carrier and Age<65 1.48 (0.63-3.47) 0.36

Adjusted for age, gender, education, current smoking, alcohol drink, physical activity score, heart disease or stroke, GDS score, APOE-ε4 allele carrying status

J Alz Dis (2013)

Am J Ger Psy (2008)

Metabolic Syndrome

Adjusted OR (95% C.I.) Cognitive Impairment

Cross-sectional analysis Longitudinal analysis

Metformin use: 0 year 1.00 1.00

≤6 years 0.74(0.33-1.67) P=0.47 0.66(0.38-1.16) p=0.15

>6 years 0.31(0.12-0.83) P=0.019 0.27(0.14-0.52) p=<0.001

Linear trend, p P=0.023 p=<0.001

¶ Adjusted for age, gender, education, baseline depressive symptoms (for whole sample), hypertension, cardiovascular

illness or stroke, other medical co-morbidity, other anti-diabetic use, APOE-4 carrier status, fasting blood glucose, BMI and

duration of diabetes.

Metformin use in Diabetic Individuals

Manuscript under review

Prediabetic and diabetic patients

with mild cognitive impairment

Lower insulin resistance

Intensive lifestyle interventions

and metformin

Randomization

Brain glucose hypometabilism (FDG-PET)

Cognitive function

• Insulin Resistance and Mild Cognitive Impairment (MCI) in Older Adults

with Pre-Diabetes and Diabetes: Cognitive Effects of Lifestyle

Intervention and Metformin Treatment • National Medical Research Council NMRC CIRG12may033

Randomized controlled trial

Standard care

Serum Folate Plasma Homocysteine

Am J Clin Nutr. 2006 Dec;84(6):1506-12.)

Immediate Recall

Delay Recall

Verbal Learning

Forgetting %

Language

-0.2

-0.15

-0.1

-0.05

0

0.05

0.1

0.15

0.2

Global Language

Executive

Control Processing

Speed

Visuo-

construction -0.35

-0.25

-0.15

-0.05

0.05

Depression

Medical comorbidity, health service use

Depression and health service use

Depressive symptoms: 13%

1 in 3 seek treatment

Help seeking:

◦ More likely:

−Psychiatric diagnosis (OR=5.27)

−Disability from mental problem (OR=79.9)

−Poor or fair self-rated mental health (OR=2.63)

−Women (OR=2.25)

−More formal education (OR=2.40)

−Believe ‘to a great extent mental illness can be cured’ (OR=6.89)

−Less likely:

−Have financial limitations for medical care (OR=0.38)

−Higher household income (OR=0.31)

−Availability of family caregiver (OR=0.20)

(Clin Pract Epidemol Ment Health. 2009 Jan 19;5:2)

2

3

4

5

6

7

8

9

10

Baseline 3 Month 6 Month 12 Month

GD

S S

co

re

Non-Participants (N=120) Usual Care (N=112) Collaborative Care (N=102)

RCT: Community outreach

screening, psychoeducation,

primary care treatment of

depressive symptoms

Increases treatment rates

from 10.3% to 73.8% (Int J Ger

Psychr, 2009)

Significantly reduces

depressive symptoms and

improves quality of life (Manuscipt in preparation)

30

35

40

45

50

Baseline 3 Month 6 Month 12 Month

SF

-12 M

CS

Non-Participants (N=120) Usual Care (N=112) Collaborative Care (N=102)

CEPIS project

Major depressive disorder

Chinese 2.8%

Malays 6.5%

Indians 6.8%

Malays and Indians have more

somatic symptoms of

depression (Int J Geriatr Psychiatry.

2008 ).

0

1

2

3

4

5

Decreased appetite

Interrupted sleep, early awakening

Disabling pain

Slow moving Low energy Difficulty remembering

hallucination &/or delusion

Feeling indecisive

Chinese Malay Indian Odds Ratio

Acknowledge

mental illness Disabled for

> 12 months

Perceived

need

for help

Sought

help of

professionals

Takes

medications

0

5

10

15

20

25

30

Non-Case Sub-Case Case

Percentage %

Ethnic differences

Sub-syndromal symptoms

Sub-syndromic depressive

symptoms are as disabling as

major depression (Int

Psychogeriatrics 2008).

Risk Factors

Older age (75+)

Less education and lower income

Poor social network and support

Chronic medical illnesses and physical

disability (Int J Ger Psychiatry2007) Depressive symptoms %

0

5

10

15

20

25

30

No disability IADL disability Only

BADL w/wo IADL Disability

Depressive symptoms %

0

5

10

15

20

25

30

No chronic illness 1-2 chronic illnesses

≥3 chronic illnesses

Depressive symptoms %

Living alone and loneliness

Living alone is

associated with 2-3x

increased mortality risk

among men

1.33 1.16

4.17

5.13

0

1

2

3

4

5

6

Not living alone Live alone

Not lonely Lonely

Depressive symptoms

1 1 1.22

2.82

0

1

2

3

Women Men

Live with Others Live alone

Mortality Relative Risk

Loneliness worsens the

psychological effects of

living alone

Comorbidity Impact

• Increases physician visits

and hospitalization

episodes (Int Psychogeriatrics, 2006)

• Increases hospital length of

stay and mortality in COPD

patients (Arch Intern Med. 2007 )

0.58

0.93

2.48

1

0.00

0.50

1.00

1.50

2.00

2.50

3.00

None Dementia

only

Depression

only

Depression

and

Dementia

Relative Risk of Hospitalization for chronic Illnesses

0 100 200 300 400

Days from discharge

Survival Probability

Relative risk of hospitalization

COPD Patients

Standard care

Depression screening,

psychoeducation,

psychological

interventions

Randomization

COPD Outcomes

FEV1

Exacerbations

Hospitalization rates

Mortality

• Consultation Liaison and Integrated Care for COPD patients with

Psychiatric Co-Morbidity

• MOH Health Service Research HSRG0016/2010

Randomized controlled trial

Population Trends and Attributable Risks

Physical Function

Functional disability

Increasing prevalence in recent decades

Contrast declining prevalence in West

Risk Factors and Correlates OR

P<0.05

Age (vs 60-69)

70-79 4.4

80+ 13.6

Female gender 2.9

Indian ethnicity 2.1

Living with others 5.7

Poor-Fair self-rated health 3.5

Self-reported chronic condition

Arthritis 2.2

Urinary problems 4.6

Stroke 6.9

Asthma/ COPD 7.6

Hip fracture 34.9

Kidney failure 24.2

Cognitive functioning

MMSE 24+ 1.0

MMSE 19-23 4.7

MMSE ≤18 10.5

Hearing impairment 3.1

Visual impairment 2.5

J Am Ger Soc 2006; 54:21–29.

• Arthritis and cognitive impairment are the leading modifiable causes of physical functional disability

Balance, gait and daily living activity function

Malnutrition

Manuscript in preparation

Pre-frail and Frail Elderly

Usual care

Nutritional

Intervention

Randomization

Cognitive performance, depressive symptoms

Dexa Body Composition (DEXA), Gait, balance, strength performance, activity of daily living performance

Folate, B12, homocyteine, Inflammatory biomarkers, bone turnover markers,

Frailty status, quality of life

• Randomized Controlled Trial of Community-based Nutritional, Physical

and Cognitive Training Intervention Programmes for At Risk Frail Elderly

• MOH NMRC/1108/2007

Randomized controlled trial

Physical

Intervention

Cognitive Training

Intervention Combined

Intervention

Successful Ageing

Dimensions of Successful Aging (Chinese aged 65+)

%

Total sample size at baseline 1,28

1 1. Physical health and well functioning, % 47.9

Good or excellent self-reported health status

and

64.6

Independent in instrumental ADL 67.1

2. Cognitive and emotional well functioning, % 61.2

MMSE ≥26 and 68.1

GDS <5 87.0

3. High social functioning and active life

engagement, %

78.4

Engaged in at least one social activities and 82.8

Engaged in at least one productive activities 90.7

4. High life satisfaction (score <11), % 88.2

Successful aging#, % 28.6

# Combined criteria (1 and 2 and 3 and 4)

Successful Ageing Determinants

Age single year (OR=0.90)

Female gender (OR=1.37)

≥6 years of education (OR=2.31)

Better housing (OR=1.41)

Religious or spiritual beliefs (OR=1.64)

Physical activities and exercise (OR=1.90)

Low or no nutritional risk (OR=2.16)

Am J Ger Psychiatry (2009)

0

1

2

3

4

5

No life event 1 or 2 life

events

3 or more life

events

GDS

Low resilience

Moderate to high resilience

30

40

50

60

No life event 1 or 2 life

events

3 or more life

events

SF-36 Mental Health Functioning

Low resilience

Moderate to high resilience

4

5

6

7

8

No life event 1 or 2 life

events

3 or more life

events

Self-rated Successful Ageing

Low resilience

Moderate to high resilience

Resilience, Stressful Life

Events and Subjective

Well-Being

Manuscript in preparation

6.8

7.2

6

5

6

7

8

Chinese Malay Indian

% Self-Rated Successful Ageing

45.2

57.7

33.3

20

40

60

80

Chinese Malay Indian

% Satisfied with Life 11.1

1.9

4.8

0

3

6

9

12

Chinese Malay Indian

% Very Good or Excellent Health

1.68 1.81

2.28

1

1.5

2

2.5

Chinese Malay Indian

Mean Number of Chronic Diseases

Ethnic differences Manuscript in preparation

Thank You