Cognitive ageing: does midlife matter?
Archana Singh-Manoux
a.singh-manoux@ucl.ac.uk
Funding
Medical Research Council, UK (K013351)
British Heart Foundation (RG/13/2/30098)
National Institutes of Health (R01AG013196, R01AG034454)
Cognitive ageing: importance of heterogeneity
peak function
Cognitive function
rates of decline
20 years
Age
65 years
Dementia (AD): the focus of research
Cognitive function
• Biases in studies starting at older ages
• Inconsistent relationship between brain structure & function
Dementia
20 years
Age
65 years
Selection bias
• smoking
Alonso et al., JNNP 2009
Atherosclerosis Risk in Communities
Reverse causation
• BMI
Fitzpatrick et al. Arch Neurol 2009
Cardiovascular Health Study
BMI at 50 years
BMI at 65 years
BMI
HR (95% CI)
HR (95% CI)
< 20 kg/m2
1.1 (0.6, 1.9)
1.6 (1.1, 2.4)
20-25 kg/m2
ref
ref
25-30 kg/m2
1.1 (0.9, 1.4)
0.9 (0.8, 1.2)
>30 kg/m2
1.4 (1.0, 1.9)
0.8 (0.6, 1.1)
Brain structure
and function
Nelson et al., J Neuropathol Exp Neurol 2009
Cognitive function
Dementia
20 years
Age
65 years
RESEARCH QUESTIONS
• Heterogeneity: cognitive decline before age 65?
• Predictors of cognitive decline
Does mid-life
matter?
Cognitive decline before the age of 65?
Hedden et al. Nat Rev Neurosci 2004
The Whitehall II Study: Cognitive Ageing
Cognitive decline before the age of 65?
1997
MEN
N=5198
WOMEN
N=2192
45-49 years
50-54 years
55-59 years
60-64 years
65-70 years
1113
1578
1083
1049
375
413
582
497
515
185
Singh-Manoux et al. BMJ 2012
Our conceptual model
Education and cognitive function
Education
50
60
70
80
60
50
40
20
20
30
40
50
60
Occupational position
30
40
30
20
Reasoning
Reasoning
50
60
Height
50
Age
High
Intermediate
60
70
80
50
Age
Low
High
Intermediate
60
70
80
Age
Low
High
Intermediate
Low
Singh-Manoux et al. Ann Neurol 2011
Educational interventions to slow cognitive decline?
Singh-Manoux Int J Epidemiol 2010
• Boost peak function, improve education for all
• Cognitive training for adults?
Smoking history and cognitive decline
Global cognition
0
-0.1
Current
-0.2
-0.3
Recent ex
Long term ex
Never
-0.4
-0.5
Sabia et al. JAMA Psychiatry 2012
Prevention
Smoking cessation messages
ought also to target older adults
Cardiovascular risk in midlife
Framingham risk scores in midlife & cognitive decline
Prevention
What is good for the heart
may be good for the head
Kaffashian et al. Neurology 2013
Diabetes & cognitive ageing
1985/88
Diabetes
1991/93
Diabetes
1997/99
Diabetes
1997/99
Cognition
2002/04
Cognition
2007/09
Cognition
Results
• Greater decline in those with diabetes.
• In diabetics, decline faster in those with poorly controlled diabetes
Tuligenga et al. Lancet Diabetes & Endocrinol 2014
Implications of good glycaemic control?
• Animal models: metformin extends lifespan
• In humans, some evidence of decreased risk of cancer, longer life expectancy
• Targeting Aging With Metformin (TAME) study to test effects on functional decline
Inflammatory factors & ageing
Inflammatory factors as mediators
Lung
function
Inflammation & cognition
Mortality
Motor
function
Inflammatory
factors
Sabia et al. Am J Epidemiol 2010
Elbaz et al. Age 2013
Singh-Manoux et al. Neurology 2014
Inflammatory factors & ageing
Inflammatory factors as mediators
Lung
function
Inflammation & cognition
Mortality
Motor
function
Inflammatory
factors
Sabia et al. Am J Epidemiol 2010
Elbaz et al. Age 2013
Singh-Manoux et al. Neurology 2014
INFLAMMAGING
Does midlife matter?
Timing
When is midlife?
Risk factors
Obesity?
Does midlife matter?
Examine cognitive decline and dementia
Examine multiple determinants
thank you