Prevention, health promotion & early intervention in dementia

Transcription

1 Prevention, health promotion & early intervention in dementia Alzheimer New Zealand Conference 2014 Steve Iliffe Professor of Primary Care & Older People University College London Rotorua, New Zealand

2 Take home messages 1. The prevention of dementia is already underway 2. Preventive activities (and beneficial social trends) may already be working 3. Obesity & diabetes could undo the benefits already acheived 4. Downstream prevention needs more research 2

3 The scale of dementia Bowman C et al J R Soc Med. 2014;107(3):95-8. Causes of death "progressive dwindling" Long term conditions Sudden death Cancer 3

4 Down with dementia! Liam Drew, New Scientist 11 th January 2014 Dementia as a tractable problem Accumulating exposures (to harm or benefit) over decades - a life-course view Modern life, with its constant multimedia inputs, may be much more stimulating than it was 50 years ago 4

5 What is dementia? A disease? Still in flux Henry Brodaty A disability? - Kate Swaffer A variant of normal ageing? 5

6 Is dementia a long-term condition? Median 7.1 years with Alzheimer s dementia, 3.9 years with vascular dementia. Fitzpatrick et al J Neurological Sciences years from symptom onset Xie J et al BMJ 2008; 336: years from diagnosis Rait et al, 2010 Aug 5;341:c3584. doi: /bmj.c

7 Is dementia a problem of memory? Subjective memory complaints strongly associated with depression Not the worried well : QoL low, service use high Depression predicts dementia Screening for memory loss? (Only 18% of future dementia cases will be identified in the preclinical phase by investigating those who screen positive for memory complaints) Palmer et al BMJ Feb 1;326(7383):245 7

8 The scale of subjective memory complaints 60% of middle-aged people reported forgetfulness that hindered them significantly 70% with SMC were very worried about it Commissaris et al Patient Education and Counselling 1998; 34(01): to 50% of older people increases with age 43% in people aged 65-74, 88% in over 85s Larrabee & Crook Int Psychogeriatrics 1994; 6(01):

9 Forgotten symptoms in dementia? Behavioral & psychological symptoms Seen in: 40% of mild cognitive impairment 60% of patients in early stage of dementia Affect % of patients with dementia at some point in the course of their illness Get more frequent and troublesome with advancing dementia 9

10 What predicts dementia? Statin use reduces dementia risk by 13-38% Kmietovic Z BMJ 2014;348:g2370 Sleeping too much or too little in midlife predicts worse cognition Devore EE et al Journal of the American Geriatrics Society 2014 doi: /jgs Helicobacter infection predicts dementia Baudron CR et al Journal of the American Geriatrics Society 2012 doi: /jgs Vitamin D seems to be protective McCarthy M BMJ 2014;349:g5049 Short leg length, limited education, low status jobs, early parental death World Alzheimer s Report

11 Where is the effective medication? Cholinesterase inhibitors Memantine Failure to develop disease-modifying drugs One pathology (B amyloid & tau), one disease (Alzheimer s), one treatment 11

12 What s cause & what s effect in dementia? Amyloid plaques and neurofibrillary tangles, but no dementia Dementia but no plaques or tangles Lock M, The Alzheimer Conundrum: entanglements of dementia and ageing Princeton University Press

13 Is dementia increasing or decreasing? Later-born populations have a lower risk of prevalent dementia than those born earlier in the past century. CFAS1 predicted prevalence in 65 population of 8.3% in 2011 CFAS2 found 6.5% Matthews FE et al Medical Research Council Cognitive Function and Ageing Collaboration. Lancet Oct 26;382(9902):

14 More evidence of declining prevalence US Health & Retirement study US Framingham study 5 year waves: 1 st 17% reduction, 2 nd 32% reduction, 3 rd 42% German AOK : 2004/7 2007/10 26% fall in incidence Spain, Sweden, Netherlands Diagnosis age being pushed back? World Alzheimer s Report

15 Back to basics? (How to think and talk about dementia) Brain cell death causes dementia Many things kill brain cells Some things protect brain cells Extent of brain function (Cognitive Reserve) matters Andrade-Moraes CH et al Brain 2013;136:

16 Brain cell deaths Cognitive Impairment Dementia 16

17 Amyloid-B and Tau toxicity Amyloid plaques & neurofibrillary tangles Brain cell deaths Cognitive Impairment Dementia 17

18 Amyloid-B and Tau toxicity Amyloid plaques & neurofibrillary tangles Genetic factors Brain cell deaths Cognitive Impairment Dementia Oxidative stress, hormones Atherosclerosis Inflammation Infection Sleep disturbance, depression 18

19 Brain protection REST Repressor element1-silencing transcription factor Present in normal ageing of cortical and hippocampal cells Lost in mild cognitive impairment and Alzheimer s disease Switches off genes promoting cell death Switches on genes protecting against stress Lu T et al Nature 2014;507:

20 - Amyloid-B and Tau toxicity Amyloid plaques & neurofibrillary tangles High REST neuroprotection - - Genetic factors Brain cell deaths Cognitive Impairment Dementia Oxidative stress, hormones Atherosclerosis Inflammation Infection Sleep disturbance, depression 20

21 - Amyloid-B and Tau toxicity Amyloid plaques & neurofibrillary tangles Healthy Ageing High REST neuroprotection - - Genetic factors Brain cell deaths Cognitive Impairment Dementia Oxidative stress, hormones Atherosclerosis Inflammation Infection Sleep disturbance, depression 21

22 - Amyloid-B and Tau toxicity Amyloid plaques & neurofibrillary tangles Healthy Ageing High REST neuroprotection - - Genetic factors Brain cell deaths Cognitive Impairment Dementia Oxidative stress, hormones Not smoking, limited alcohol, more physical activity, statins, BP control, treated depression? Diet? Atherosclerosis - Inflammation Infection Sleep disturbance, depression 22

23 - Amyloid-B and Tau toxicity Amyloid plaques & neurofibrillary tangles Healthy Ageing High REST neuroprotection Oxidative stress, hormones Genetic factors Not smoking, limited alcohol, more physical activity, statins, BP control, treated depression? Diet? Brain cell deaths Inflammation Infection Cognitive Impairment Dementia Increase cognitive reserve Atherosclerosis - Education, brain stimulation Sleep disturbance, depression? 23

24 So what do we do? NICE (National Institute for Health & Care Excellence) Dementia, disability & frailty in later life mid-life approaches to prevention (2015) NIH State-of-the-Science Consensus statement: Preventing Alzheimer s disease and cognitive decline (2010) Blackfriars consensus on promoting brain health (Public Health England 2014) World Alzheimer s Report (2014) 24

25 Upstream: primary prevention Reducing poverty, enhancing educational opportunities Intrinsically good? Smoking cessation Evidence stronger for Alzheimer s disease than vascular dementia BP control in midlife Increase habitual physical activity In midlife rather than later life (reverse causality) Reduce heart disease: statins Prevent diabetes Midlife and later life effects on dementia risk 25

26 Downstream: secondary prevention Cognitive stimulation therapy NICE/SCIE Dementia clinical guidelines 2006 Memory training limited evidence of effect Martin M et al Cochrane Database Syst Rev 2011 Goal oriented cognitive rehabilitation improves goal performance & satisfaction Clare L et al Am J Geriatr Psychiatry 2010; 18: Intergenerational relationships Whitehouse P J Alzheimers Disease 2013;36: Compensatory strategies, carer education & support, meaningful activities Laver K et al Phys & Occup Ther Geriatr 2014;1-16 Physical activity assists carers? Lowery D Int J Geriatr Psychiatry. 2014;29(8):

27 Lowery D et al The effect of exercise on behavioural and psychological symptoms of dementia: the EVIDEM-E randomised controlled clinical trial. Int J Geriatr Psychiatry. 2014;29(8): week individually tailored walking programme, progressively intensive, min, at least 5 times per week. Community-dwelling individuals with ICD-10 confirmed dementia clinically significant behavioural and psychological symptoms a carer willing and able to co-participate in the exercise, No physical conditions/ symptoms precluding exercise participation No significant difference in BPSD measured with NPI at week 12 between groups (adjusted difference in means (intervention minus control) = -1.53, p = 0.6, 95% CI [-7.37, 4.32]). Significant difference in caregiver's burden (Zarit Caregiver Burden Inventory) at week 12 favouring exercise group (OR = 0.18, p = 0.01, CI [0.05, 0.69]). 27

28 In summary The prevention of dementia is already underway (under other names) Preventive activities (and beneficial social trends) may already be working Obesity & diabetes will challenge prevention plans Downstream prevention needs more research, but there are promising interventions Thank you for listening! 28