Diverse Communities C ollective Action Alzheimer New ZealandADI Conference 2016 Steve Iliffe Emeritus Professor of Primary Care for Older People University College London 3 rd 5 ID: 529132
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Dementia todayDiverse Communities, Collective ActionAlzheimer New Zealand/ADI Conference 2016
Steve IliffeEmeritus Professor of Primary Care for Older PeopleUniversity College London
3
rd
– 5
th
November, Wellington, New ZealandSlide2
Determinants of dementiaAboriginal and Torres Strait Islander people experience dementia at a rate 3 to 5 times higher than the general Australian population.Aboriginal And Torres Strait Islander People And Dementia: A Review Of The Research
A Report For Alzheimer's Australia Paper 41 October 2014 Professor Leon Flicker and Kristen Holdsworth
2Slide3
More is less?We know so much more about dementia. Medically we can do little more for it than 20 years ago
“Gnawing controversies and important gaps in our knowledge seem to cast additional doubt on the ability of the field to move forward effectively” Selkoe, DJ. (2011) Resolving controversies on the path to Alzheimer’s therapeutics
Nature Medicine
; 17(9) 1060-1065
.
3Slide4
What’s cause & what’s effect in dementia?Amyloid plaques and neurofibrillary tangles, but no dementiaDementia but no plaques or tangles
“The amyloid hypothesis for Alzheimer’s disease (AD) posits a neuron-centric, linear cascade .. leading to dementia. This direct causality is incompatible with clinical observations”.De Strooper B. and
Karran
E. (2016) The Cellular Phase of Alzheimer’s Disease
Cell
164: 603-615
.
4Slide5
Where is the effective medication?Cholinesterase inhibitors + Memantine ….clinical benefits are probably negligible at a population level
Lin, J.S., et al (2013) Screening for cognitive impairment in older adults: a systematic review for the US Preventive Services Task Force. Annals of Internal Medicine, 159, 601-612.Failure to develop disease-modifying drugs
“Promissory medicine”
Research fatigue
5Slide6
Is cure realistic?“… we need to acknowledge that a single cure for Alzheimer's disease is unlikely to be found and that the approach to drug development for this disorder needs to be reconsidered”.
Mangialasche, F, et al Alzheimer's disease: clinical trials and drug development. Lancet Neurol 2010;
9 (7) 702-16
.
6Slide7
The crisis in biomedicineA combination of ever-deeper knowledge of subcellular biology, coupled with information technology will lead to transformative improvements in health care and human
health…... this approach has largely failed. Joyner MJ, Paneth N, Ioannidis JPA What Happens When Underperforming Big Ideas in Research Become Entrenched? JAMA. 2016;316(13):1355-1356. doi:10.1001/jama.2016.11076
7Slide8
Pessimism is unwarranted.We have clear indications about what to do.Incidence and prevalence seem to be decliningPreventive activities (against heart disease) are brain-protective
Mechanisms protecting brain cells are becoming clearerNeuroplasticityCognitive reserve8Slide9
What is dementia syndrome?Memory loss + one other cognitive loss, causing impairmentA disease?A variant of normal ageing?A disability?A type of frailty?
9Slide10
Origins of dementia syndromeEarly-life childhood and adolescent environment increases risk of AD (especially large family size) The brain areas that show the earliest signs of AD are the same areas
that take the longest to mature during childhood and adolescence. Moceri VM et al. Early-life risk factors and the development of Alzheimer's disease Neurology. 2000 Jan 25;54(2):415-20.
10Slide11
What else predicts cognitive impairment or dementia?Genetic susceptibilityStatin use reduces dementia risk by 13-38%
Kmietovic Z BMJ 2014;348:g2370Sleeping too much or too little in midlife Devore EE et al Journal of the American Geriatrics Society 2014 doi: 10.1111/jgs.12790Helicobacter infection
Baudron
CR et al
Journal of the American Geriatrics Society
2012 doi:10.1111/jgs.12065
Short leg length, limited education, low status jobs, early parental death, Vitamin D deficiency
World Alzheimer’s Report 2014
Married, living with others, not being lonely appear protective
Gow
A, Mortensen E Social resources and cognitive ageing across 30 years Age & Ageing 2016: 45; 480-6
11Slide12
Is dementia increasing or decreasing?Later-born populations have a lower risk of prevalent dementia than those born earlier.CFAS1 predicted prevalence in 65+ population of 8.3% in 2011
In 2011 CFAS2 found 6.5% Matthews FE et al Medical Research Council Cognitive Function and Ageing Collaboration. Lancet. 2013 Oct 26;382(9902):1405-12
12Slide13
Different perspectives on dementia Accumulating exposures (to harm or benefit) over decades (disorder of the life-course)Part of a triad of impairment: cognitive, emotional (depression) and physical (frailty)
Chapko D et al Late-life deficits in cognitive, physical and emotional functions Age & Ageing 2016;45: 486-493A short-term condition: 4.5 years from symptom onset
Xie
J et al BMJ 2008; 336:
258-262,
3.5
years from
diagnosis
Rait
et al, 2010 Aug 5;341:c3584.
doi
: 10.1136/bmj.c3584
13Slide14
Back to basics?Brain cell death causes dementiaMany things kill brain cellsSome things protect brain cellsExtent of brain function (Cognitive Reserve) matters
Andrade-Moraes CH et al Brain 2013;136:3738-375214Slide15
Dementia
CognitiveImpairment
Amyloid-B and Tau toxicity
Amyloid plaques & neurofibrillary tangles
+
Atherosclerosis
Inflammation
Infection
+
+
Brain cell deaths
Genetic factors
Oxidative stress, hormones
Sleep disturbance, depression
15Slide16
Brain protectionREST Repressor element1-silencing transcription factorPresent in normal ageing of cortical and hippocampal cellsLost in mild cognitive impairment and Alzheimer’s diseaseSwitches off genes promoting cell deathSwitches on genes protecting against stress
Lu T et al Nature 2014;507:448-45416Slide17
Dementia
CognitiveImpairment
Amyloid-B and Tau toxicity
Amyloid plaques & neurofibrillary tangles
+
Atherosclerosis
Inflammation
Infection
+
+
Brain cell deaths
Genetic factors
Oxidative stress, hormones
Sleep disturbance, depression
-
-
High REST neuroprotection
-
17Slide18
Dementia
CognitiveImpairment
Amyloid-B and Tau toxicity
Amyloid plaques & neurofibrillary tangles
+
Inflammation
Infection
+
+
Brain cell deaths
Genetic factors
Oxidative stress, hormones
Sleep disturbance, depression
-
-
-
+
+
“Healthy Ageing”
High REST neuroprotection
Not smoking, limited alcohol, more physical activity, statins, BP control, treated depression? Diet?
-
Atherosclerosis
18Slide19
+
-
Dementia
Cognitive
Impairment
Amyloid-B and Tau toxicity
Amyloid plaques & neurofibrillary tangles
+
Inflammation
Infection
+
+
Brain cell deaths
Genetic factors
Oxidative stress, hormones
Sleep disturbance,
depression?
-
-
+
+
“Healthy Ageing”
High REST neuroprotection
Not smoking, limited alcohol, more physical activity, statins, BP control, treated depression? Diet?
-
Atherosclerosis
-
Increase
cognitive
reserve
Education,
brain stimulation, social resources
19
-
Brain-derived
neurotrophic factor (BDNF
),
Vascular endothelial growth factor (VEGF)
-Slide20
Cognitive reserve‘Modern life, with its constant multimedia inputs, may be much more stimulating than it was 50 years ago’
Liam Drew, Down with Dementia! New Scientist 11th January 2014
20Slide21
Collective action - what do we do?Prevention is more valuable than treatment for most real-world situations Rheinberger et al The value of disease prevention vs treatment J Health Economics August 2016
‘Echopsychosocial’ approach (Whitehouse)Long term, low-level activities in civil societyPromote healthy living and ageingIncrease cognitive reserveNot highly profitable
Nobel prizes unlikely
21Slide22
Collective action - Upstream: primary preventionReducing poverty, enhancing educational opportunitiesSmoking cessation Evidence stronger for Alzheimer’s disease than vascular dementia
BP control in midlifeIncrease habitual physical activity In midlife rather than later life (reverse causality)Reduce heart disease: statinsPrevent diabetes Midlife and later life effects on dementia risk
22Slide23
Collective action - Reducing poverty 1In the USA between 1972 and 1977, social security payments for people born between 1910 and 1916 increased faster than inflation.
A $1000 (in 1993 prices) increase in annual income lead to a 1.9 percentage point reduction in the likelihood of being classified as cognitively impaired. The additional income resulted in improvements in working memory, knowledge, languages and orientation and overall cognition.
Ayyagari
P,
Frisvold
D The Impact of Social Security Income on Cognitive Function at Older Ages American Journal of Health Economics 2016 doi:10.1162/AJHE_a_00058
23Slide24
Collective action - Reducing poverty 2Between 1999 and 2012 about 800 million people escaped from povertyPoverty ~ less than $1.90/day of income or consumption
Cruz M et al Ending extreme poverty and sharing prosperity World Bank Policy Research Note/15/03 October 201524Slide25
Collective action - Downstream: secondary preventionDementia friendly communitiesIntergenerational relationships Whitehouse P J Alzheimers
Disease 2013;36: 225-232Compensatory strategies, carer education & support, meaningful activities Laver K et al Phys & Occup Ther
Geriatr
2014;1-16
Physical
activity
Lowery
D
Int
J
Geriatr
Psychiatry
.
2014;29(8):819-27
Refresher courses in driving using simulators
Teasdale et al drivers with amnestic mild cognitive impairment can benefit from a multiple-session driving simulator automated training programme JAGS 2016;
doi
: 10.1111/jgs.14219
25Slide26
In summaryIt helps to think of dementia as a preventable disabilityThe up-stream prevention of dementia is already underway (under other names)Upstream preventive activities (and beneficial social trends) may already be working
Downstream prevention needs more attention, especially ecopsychosocial approachesThank you for listening! s.iliffe@ucl.ac.uk
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