Mild Cognitive Impairment
Claudia Cooper
UCL Clinical Reader
Honorary consultant old age psychiatrist, Camden and Islington NHS FT
Talk plan
• Diagnosis
• Treating MCI:
– Evidence from RCTs
– Evidence from prospective cohort studies
• Preventing dementia in preclinical populations
• Future directions
Mild Cognitive Impairment – a high risk group for dementia
• Around 20% of people over 70 have MCI (and 10%
have dementia)
• 46% of people with MCI develop dementia within 3 years compared to 3% without MCI.
What prevents MCI converting to dementia?
RCT evidence
Cognitive training
• Specific strategies improve specific functions eg memory for specific information
• Effects on general cognition no better than “active controls” (eg discussion groups) for people with
– No impairment – MCI
– dementia
• Part of some successful multicomponent interventions (eg Buschert, FINGER)
Exercise
• Younger and middle aged people who exercise have better cognition in older age
• Exercise neuroprotects:
– Releases BDNF – Reduces cortisol
• Reduces vascular risk
Exercise
• Exercise did not improve cognition in
– Healthy older adults (Cochrane, 12 trials)
– Dementia (but did improve adls) (Cochrane,9 studies)
• Evidence for MCI inconsistent, in RCT group aerobic exercise no better than relaxation
/flexibility control.
Pharmacological interventions for MCI
• ChEI and NSAIDs do not prevent dementia
• Cognition improved in single trials of:
– √ piribedil, a dopamine agonist over 3 months
– √ nicotine improved attention over 6 months.
• Inconsistent evidence: vitamins B & E, fish oils, Gingko biloba
• Nutritional (fish oils, vitamin E, tryptophan) improved cognition in one lower quality study
Cooper et al, Br J Psychiatry. 2013 Sep;203(3):255-64. Treatment for mild cognitive impairment: systematic review.
Prospective cohort study evidence
Diabetes type 2 and prediabetes
• Increased risk of Alzheimer’s disease and vascular dementia
• Increased risk of conversion from MCI to dementia
– Risk for aMCI, naMCI and any type MCI – Higher rate for untreated diabetes
Cooper et al, Modifiable predictors of dementia in mild cognitive impairment: a systematic review and meta-analysis AJP April 2015
Odds ratios for risk of dementia in people with and without diabetes
0.01 0.1 0.2 0.5 1 2 5 10 100
Velayudhan (Clin, aMCI>D) Solfrizzi 2004 (Ep, aMCI>D) Ravaglia (Clin, aMCI>AD)
Prasad (Clin, aMCI>AD) Li 2011 (Ep, aMCI>AD)
Artero (Ep, MCI>D) Xu 2010 (Ep, MCI>D)
combined [random] 1.65 (1.12, 2.43)
odds ratio (95% confidence interval)
Why does diabetes increase risk of dementia?
• Damage to blood vessels (atherosclerosis, glucose- mediated toxicity)
• Brain infarcts
• High blood insulin levels (in type II diabetes and insulin replacement) cause
– vascular disease
– direct brain effects; insulin inhibits beta amyloid degradation
Other vascular risk factors: MCI to dementia conversion
Metabolic syndrome = 3+: obesity; ↑plasma TG; ↓HDL cholesterol;
hypertension; ↑ fasting glucose) Cooper et al, AJP 2015
Pre MCI
MCI
Hypertension √ X
High cholesterol √ X
Smoking √ X
Metabolic syndrome
√ √
Figure 2b: Odds ratios for current hypertension
0.1 0.2 0.5 1 2 5 10 100
Korf (Clin, MCI>D) 0.45 (0.13, 1.45)
Oveisgharan (Ep, MCI>D) 0.81 (0.61, 1.08)
Artero (Ep, MCI>D) 1.96 (1.25, 3.21)
Ravaglia (Clin, aMCI>AD) 1.23 (0.58, 2.57)
Solfrizzi 2004 (Ep, aMCI>D) 1.86 (0.45, 10.97)
Prasad (Clin, aMCI>AD) 0.92 (0.31, 2.71)
Li 2011 (Ep, aMCI>AD) 1.61 (1.14, 2.26)
combined [random] 1.19 (0.81, 1.73)
odds ratio (95% confidence interval)
Neuropsychiatric symptoms
• depression increases dementia risk 2-5x
• tentative evidence antidepressants may have neuroprotective abilities
Figure 2f: Odds ratio, Neuropsychiatric symptoms
0.01 0.1 0.2 0.5 1 2 5 10 100
Rosenberg 2013 (Clin, MCI>D) 1.86 (1.53, 2.26)
Edwards 2009 (Clin, MCI>D) 1.61 (0.86, 3.10)
Taragano (Clin, MCI>D) 7.51 (3.96, 14.29)
Teng (Clin, MCI>AD) 17.55 (1.60, infinity)
Brodaty 2012 (Epi, MCI>D) 0.64 (0.07, 3.25)
combined [random] 2.52 (1.18, 5.37)
odds ratio (95% confidence interval)
Figure 2d: Odds ratios for depressive symptoms
0.01 0.1 0.2 0.5 1 2 5 10 100
Richard 2012 (Clin, aMCI>AD) 1.86 (1.21, 2.87)
Palmer 2010 (Clin, aMCI>AD) 0.95 (0.23, 3.41)
Visser 2000 (Clin, aMCI>AD) 0.57 (0.14, 2.09)
Fellows (Clin, aMCI>AD) 0.76 (0.30, 1.94)
Modrego (Clin, aMCI>AD) 11.91 (4.11, 38.57)
Velayudhan (Clin, aMCI>D) 1.59 (0.38, 6.24)
Panza 2008 (Ep, aMCI>D) 0.83 (0.23, 3.12)
Caracciolo (Ep, aMCI>D) 3.28 (0.60, 22.48)
Chilovi (Clin, MCI>D) 0.28 (0.09, 0.78)
Korf (Clin, MCI>D) 0.48 (0.17, 1.35)
Chan (Clin, MCI>D) 2.18 (0.99, 4.57)
Artero (Ep, MCI>D) 1.95 (1.36, 2.77)
Richard 2013 (Ep, MCI>D) 1.70 (0.91, 3.08)
combined [random] 1.35 (0.89, 2.06)
odds ratio (95% confidence interval)
Figure 2e Apathy Odds ratio
0.01 0.1 0.2 0.5 1 2 5 10 100
Chan (Clin, MCI>D) 0.34 (0.06, 1.14)
Chilovi (Clin, MCI>D) 2.75 (1.03, 7.21)
Robert (Clin, aMCI>AD) 2.39 (0.89, 6.66)
Richard 2012 (Clin, aMCI>AD) 0.72 (0.47, 1.09)
Palmer 2010 (Clin, aMCI>AD) 8.67 (1.83, 39.44)
combined [random] 1.62 (0.63, 4.17)
odds ratio (95% confidence interval)
Education
Education predicts dementia in general population but not MCI.
Figure 2g: Effect size for years of education
-1.5 -1.0 -0.5 0.5 1.0
Korf (Clin, MCI>D) Devier (Clin, MCI>D) Chan (Clin, MCI>D) Meyer (Ep, MCI>D) Hsiung 2008 (Clin, MCI>AD) Rozzini 2007 (Clin, aMCI>AD) Prasad (Clin, aMCI>AD) Fellows (Clin, aMCI>AD) Ye 2012 (Clin, aMCI>AD) Visser 2000 (Clin, aMCI>AD) Velayudhan (Clin, aMCI>D) Mackin (Clin, aMCI>D)
0
DL pooled effect size = -0.117011 (95% CI = -0.26397 to 0.029947)
Diet
√ Higher folate levels
√ Adherence to Mediterranean diet
Mediterranean diet
• Decreases cognitive decline and reduces risk of Alzheimer’s disease
• Lots of vegetables, legumes, fruits, cereals; fish, unsaturated fatty acids (olive oil)
• low intake of saturated fatty acids; dairy products, meat and poultry;
• Regular, moderate wine during meals
Epidemiology. 2013 Jul;24(4):479-89.
Why might Mediterranean diet prevent dementia?
• It is associated with:
– Lower blood pressure – Lower bad cholesterol – Less diabetes
– Lower homocysteine levels (high homocysteine levels linked to heart disease)
• PREDIMED trial (Malaga): trained dieticians gave group and individual advice to people aged 55-80.
Reduced heart attacks, stroke and death.
Alcohol
• Heavy alcohol use harmful
• In general population, moderate alcohol consumption might be helpful
• No evidence moderate alcohol use helps people with MCI
Preventing dementia – preclinical stage
Factors increasing the risk of Alzheimer’s disease:
• Physical inactivity (UK PAF 22%)
• Depression 8%
• Midlife hypertension 7%
• Midlife obesity 7%
• Smoking 11%
• Low educational attainment 12%
• Diabetes (5%)
– Norton et al, 2014, Lancet Neurology
What are the most important predictors of dementia (in the general older population)
1. crystallised intelligence (PAF 18%) 2. depression (10%)
3. Genetic risk (apolipoprotein E ε4 allele) 7%
4. fruit and vegetable consumption (6%) 5. diabetes (5%)
BMJ. 2010; 341: c3885. Karen Ritchie
Social support
Feelings of loneliness, not actual social isolation
predicted dementia in older people (AMSTEL study) Larger social networks protected from dementia
(US/Swedish studies)
FINGER trial (Lancet, 2015)
• 1260 people with high vascular risk scores
• Cognition improved with intervention:
– Diet (3 individual and 7-9 group sessions) – Exercise (group and individual)
– Cognitive training (10 group sessions and individual computerised 3x per week)
– Regular nurse and physician management of vascular risk factors
What might a future intervention for MCI be like?
• Multimodal
• Cost-effective
Decrease further damage:
Treat vascular risk factors Diet, exercise
Maximise function: Cognitive/ social stimulation
Treat neuropsychiatric symptoms
What to tell people with MCI
• Looking after physical health and reducing excessive alcohol intake will help
• Eating well to reduce risk of diabetes and
managing existing diabetes well very likely to help.
• Staying mentally well also important.
