Tag Archives: Dementia

Does Physical or Cognitive Training Slow Decline in Cognition with Age, or Delay the Onset of Dementia?

Two careful reviews in the Annals of Medicine review current trial evidence.[1] [2] This is a hard topic to study because interventions are heterogeneous; outcomes are multiple and vary between studies, and long-term follow-up is required. As far as exercise is concerned, the evidence is simply insufficient. Cognitive training reduces cognitive decline in the particular cognitive task targeted by the training, but does not seem to produce a global effect. These studies were both based on people with normal functioning at baseline.

— Richard Lilford, CLAHRC WM Director


  1. Brasure M, Desai P, Davila H, Nelson VA, Calvert C, Jutkowitz E, et al. Physical Activity Interventions in Preventing Cognitive Decline and Alzheimer-Type Dementia: A Systematic Review. Ann Intern Med. 2018; 168: 30-8.
  2. Butler M, McCreedy E, Nelson VA, Desai P, Ratner E, Fink HA, et al. Does Cognitive Training Prevent Cognitive Decline?: A Systematic Review. Ann Intern Med. 2018; 168: 63-8.

So Where Are We up to with Alcohol and Health?

First, let me come clean – I am a moderate drinker. No doubt about it. Five nights a week on a mean of two glasses, and two nights on a mean of three glasses. These are average sized glasses, so let’s say 24 units (1.5 x 16) per week. I love wine and seek good news…

The story so far:

  1. There is a ‘J-shaped’ curve of the association between alcohol and many diseases.[1]
    093 - Alcohol j curve
    * Cancer does not follow this pattern. Cancers of mouth, throat and gullet are almost certainly increased, and probably breast too.[2]
  2. But Mendelian randomisation (inheriting genes predisposing to alcohol consumption) does not show a J-shaped curve – risk rises incrementally.[3]
  3. Longitudinal studies show that, on one dimension of cognition, decline is faster in linear relationship to alcohol dose, and this finding ‘triangulates’ with a drop in right-sided hippocampal volume (detected by MRI) in relation to alcohol intake.[4]

Conclusion: the J-shaped curve is an artefact of selection bias.

So what’s new? First, a meta-analysis of longitudinal studies [5] shows a substantial protective effect against dementia for low to moderate alcohol intake (RR 0.63, 0.53-0.75) and also in Alzheimer’s disease (RR 0.57, 0.44-0.74). Second, there some evidence from these studies that chronic drinking is protective of cognitive decline, while episodic drinking is harmful at the same total intake. Third, a new longitudinal study suggests that chronic (i.e. non-binge) drinking is indeed protective against cognitive impairment in older people.[6]

This new study (the Rancho Bernardo study) is based on a cohort of 6,339 middle-class residents of a suburb in San Diego. Of the surviving residents, 2,479 attended a research clinic in 1985 where detailed alcohol histories were elicited. The participants were followed up every four years with cognitive tests. Co-variates were collected and added sequentially to a logistic regression model, starting with those (e.g. sex and age) least likely to be on the causal pathway linking alcohol to outcome. The APOE genotype was examined as an interaction term. Potential confounding effects of diet were also examined. Various sensitivity analyses were conducted. Drinking up to 3 units per day after age 65, and 4 units per day at a younger age significantly increased the chance of healthy survival, with an odds ratio exceeding 2. The J curve is there in the data, with the probability of healthy longevity increasing through no, low, moderate and even heavy drinking, only to decline again when drinking was ‘excessive’ (meaning over 4 drinks per day aged under 65 and over 3 per day for men over 65, and 3 or 2 drinks per day in younger or older women. And, yes, more frequent drinking is better than episodic drinking at a given intake – ORs of Cognitively Health Longevity increased three-fold with daily drinking vs. not drinking at all, but only two-fold if drinking was ‘infrequent’. Conclusions were robust to various sensitivity analyses.

What is the truth? No person knoweth it! But the idea that regular, moderate drinking offers some protective effects to trade-off against cancer risk has empirical support. I wonder if there are different genes predisposing to binge vs. steady drinking? I hypothesise that the genes are associated with poor impulse control leading to binge drinking. I hope that this hypothesis will now be put to an empirical test. Another question, of course, concerns the type of drink. The middle-class people in the Rancho Bernardo study may have favoured wine over other drinks – I hope so!

— Richard Lilford, CLAHRC WM Director


  1. Di Castelnuovo A, Costanzo  S, Bagnardi  V, Donati  MB, Iacoviello  L, de Gaetano    Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies.  Arch Intern Med. 2006; 166(22): 2437-45.
  2. Lilford RJ. Oh Dear – Evidence Against Alcohol Accumulates. NIHR CLAHRC West Midlands News Blog. 7 December, 2017.
  3. Holmes MV, Dale CE, Zuccolo L, et al. Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data. BMJ. 2014; 349: g4164.
  4. Lilford RJ. Alcohol and its Effects. NIHR CLAHRC West Midlands News Blog. 18 August, 2017.
  5. Peters R, Peters J, Warner J, Beckett N, Bulpitt C. Alcohol, dementia and cognitive decline in the elderly: a systematic review. Age Ageing. 2008; 37(5): 505-12.
  6. Richard EL, Kritz-Silverstein D, Laughlin GA, Fung TT, Barrett-Connor E, McEvoy LK. Alcohol Intake and Cognitively Healthy Longevity in Community-Dwelling Adults: The Rancho Bernardo Study. J Alzheimer’s Dis. 2017; 59: 803-14.

Sniffing Out Trouble

The scent of freshly baked bread; the smell of a recently-mown lawn on a summer’s breeze; the aroma of an open bottle of wine – people often take particular delight in smell. But as we get older our olfactory function starts to decline. Interestingly, previous research has shown that adults with dementia have more difficulty distinguishing smells, compared to adults without dementia. However, we do not know whether this olfactory dysfunction is predictive of subsequent dementia.

A longitudinal study of 2,906 US adults aged 57-85 measured their ability to identify five odours (rose, leather, orange, fish and peppermint) using a validated test, then looked at the incidence of dementia five years later.[1] They found that adults who had difficulty identifying the smells at baseline were more than twice as likely to have developed dementia by the five year follow up (odds ratio = 2.13, 95% CI 1.32-3.43). This was after controlling for age, sex, race and ethnicity, education, comorbidities, and cognition at baseline. Further, more errors in identification was associated with greater probability of dementia diagnosis (p=0.04). Unfortunately, as the authors admit, they did not control for confounders already associated with olfactory function, such as smoking or depression.

It is hoped that using such an odour identification test will be an efficient and cost-effective addition to current examinations that assess an individual’s risk of dementia, thereby allowing early interventions and give individuals more time to plan for their future. It may also be a useful tool for early diagnosis of Parkinson’s disease, which is also associated with olfactory dysfunction.

— Peter Chilton, Research Fellow


  1. Adams DR, Kern DW, Wroblewski KE, McClintock MK, Dale W, Pinto JM. Olfactory Dysfunction Predicts Subsequent Dementia in Older U.S. Adults. J Am Geriatr Soc. 2017.

Coffee – Yet More Good News!

Coffee protects the liver against alcoholic cirrhosis [1] and there is previous animal and limited human evidence that it preserves cognition in older age.[2] Data on this point have now emerged from ten years follow-up of nearly 6,500 enrolees in the Women’s Health Initiative Memory study.[3] Women consuming above median caffeine intake experienced about a 25% reduction in dementia (p=0.04) or cognitive impairment (p=0.005). Surprise, surprise, caffeine modulates synaptic plasticity, discussed previously in your News Blog.[4-6]

— Richard Lilford, CLAHRC WM Director


  1. Kennedy OJ, Roderick P, Buchanan R, Fallowfield JA, Hayes PC, Parkes J. Systematic review with meta-analysis: coffee consumption and the risk of cirrhosis. Ailment Pharmacol Ther. 2016; 43(5): 562-74.
  2. Shukitt-Hale B, Miller MG, Chu YF, Lyle BJ, Joseph JA. Coffee, but not caffeine, has positive effects on cognition and psychomotor behavior in aging. Age (Dordr). 2013; 35(6): 2183-92.
  3. Driscoll I, Shumaker SA, Snively BM, et al. Relationships Between Caffeine Intake and Risk for Probable Dementia or Global Cognitive Impairment: The Women’s Health Initiative Memory Study. J Gerontol A Biol Sci Med Sci. 2016; 71(12): 1596-1602.
  4. Lilford RJ. Psychiatry Comes of Age. NIHR CLAHRC West Midlands News Blog. March 11 2016.
  5. Lilford RJ. A Fascinating Account of the Opening Up of an Area of Scientific Enquiry. NIHR CLAHRC West Midlands News Blog. November 11 2016.
  6. Lilford RJ. Okay Then, There is a Fourth Period of Whole-Scale Synaptic Pruning in the Grey Matter of the Brain. NIHR CLAHRC West Midlands News Blog. January 13 2017.

Future Trends in NHS

The future of health care is often conceptualised in terms of improved treatments emerging from the bio-medical science base – for instance increasing the precision with which particular therapies can be targeted. Many of these advances in the effectiveness of care will have supply side consequences in terms of cost and some will require service re-configuration – regenerative medicine and bed-side diagnostics, for example. However the larger challenges are likely to originate from increased demand. The service will have to adapt to these supply and demand side changes. This blog considers the role of applied research in informing these adaptations in order to improve the overall effectiveness and efficiency of services.

We discern three trends which, absent a major perturbation such as international conflict, will alter demand over the medium to long term. The time horizon for our analysis is the next quarter century, given that the longer the time horizon the wider the variance in any predictions.

The trends are as follows:

  1. The population demographic will continue towards higher proportions of elderly people.
  2. The dependency ratio (ratio of working age to young and retired people) will become increasingly adverse.
  3. Demand for services per capita will increase.

None of these assumptions is unarguable as they involve outcomes that have not yet been observed. They are ordered from least to most contentious.

  1. That the population will continue to age is almost a given, but the rate at which it will do is less certain. Some predict that over a third of children alive now will reach a century. However, the rate of increase in life expectancy may slow as the large reductions in smoking related deaths are absorbed into the base-line. Immigration could affect population projections in ways that are hard to predict. The recent sudden increase in mortality among white middle-aged males in the USA,[1] but improvement in survival of low socio-economic group children in the same country,[2] shows how difficult projections can be. A recent demonstration of trends over two decades suggests that age-specific prevalence of dementias are reducing, arguably because risk factors for cardiovascular disease are also risk factors for dementia. This will not reduce the total prevalence of dementia, of course, if life expectancy continues to increase.[3] [4]
  2. The worsening of the dependency ratio is almost a corollary of an ageing society, but again the extent to which this happens is less certain as the work force gradually internalises the notion that 65 years of age is not a biological watershed but a social convention.[5] But delayed retirement will not solve the problem of a deteriorating dependency ratio; absent a method to delay ageing, many types of work, such as aviation and mining, are simply not suitable for older people. In addition, as people work longer at the end of life; so policies are encouraging longer leaves of absence from work outside the home to care for young children. So, all things considered, the dependency ratio will become more adverse as a function of increased longevity. Note, Britain appears to be at an earlier stage in this transition than many other high-income countries, such as Japan and Germany, and the opportunity for immigration to mitigate the tendency is likely to be accentuated given recent events.
  3. Demand for services contingent on an ageing population is somewhat controversial. A reasonable planning assumption is that people will be healthier at a given age but this will not completely mitigate the frailty of older people at a given age. In that case we must assume a rise in demand as the population ages, even if age-specific morbidity declines to some extent.

Implications for the NHS flow from the above. Demand for services will increase relative to resources. That is to say there will be more old people relative to working age people and there will be more frail people relative to the population and demand will outpace economic growth. All of this may be compounded by a tendency for old people to live in remote areas at a distance from major conurbations where health services are concentrated. However, this problem will be less acute than in most other countries.

There are many possible mitigations and the NIHR has a role in all of them; these are listed in the table below.

Factors to help the service cope with increasing demand.

                  Mitigating factor How it might work Caveats Potential impact
Major technical advances that might affect demand. A ‘cure’ or prevention for dementia would both improve the economy (and hence supply) while supressing demand. Probably lies outside our 25 year time horizon. Will prolong life and hence increase the proportion of frail elderly people. Potentially very high but out of scope. Medical advances more generally likely to increase demand by increasing longevity.
Self-care An ‘extreme’ form of skill substitution. Unlike other mitigations there is an extensive research literature. Beneficial for capable patients minimal impact on global demand. The correct answer to improving care, reducing demand will require development of interventions and further research.
Information technology Can make care safer and supply more efficient. Full electronic notes disrupt patient communication in their current form. A lot more needs to be learned about the design and implementation of this deceptively complex technology. Huge benefits in prospect but the socio-technical aspects require extensive development and research.
Robotics May substitute for expensive/scarce human resources.[6] Humans require the care and attention of other humans. Moderate. Likely to assist rather than replace clinical input.
Skill substitution Less expensive staff (physician’s assistants) substitute for more expensive (doctors). Increasingly feasible as health care increasingly codified. Limited by the complexity of decision making in patients with many diseases. Very hard to say without more research. May be modest.
Pro-active community services Prevent deterioration to improve health and decrease admissions. Existing research disappointing – may actually increase demand by identifying self- correcting illness. Potentially great but we are in the foothills of discovery.

Mitigating demand is not easy in the face of the demographic factors mentioned above. It is often argued, even in official enquiries, that prevention is the key to reducing demand. While prevention may reduce demand arising from particular diseases, such as diabetes, survivors go on to develop further diseases on their trajectory to death.[7] It is therefore not at all clear that prevention will reduce total demand and it may even be the case that deferred demand is augmented demand. There are some potential mitigating possibilities. A prevention or cure for Alzheimer’s disease would make a massive difference. Less distant is an ‘artificial pancreas’ that might massively simplify diabetes care. Methods to make people independent, such as home telemetry, have had nugatory impact on demand to date,[8] but this may change in the future. Patient self-care is beneficial in improving healthcare and satisfaction,[9] but effects on total demand have been modest.

If supply side measures might help services cope with the consequences and demand continues to rise, then two points should be noticed. First, efficiency gains are notoriously difficult to achieve in service industries. Second, the likely increasingly adverse dependency ratio is likely to limit expansion in skilled staff. Partial solutions may lie in manufacturing, including robotics and information technology. Skill substitution is a future area where it may be possible to improve efficiency.[10] In particular, physicians assistants may reduce costs overall.[11] The research for skills or system substitution is not entirely positive – for example, substituting nurses for doctors may not improve efficiency because consultation times had to increase.[12] There is an international trend to provide more care at ‘grass roots’ by means of Community Health Workers (CHWs) – an area where high-income countries are learning from low- and middle-income countries.[13] CHWs have a large potential role in improving care – helping patients to adhere to medications, providing preventative services, identifying deteriorating patients. Their effect on reducing demand is less certain, and on occasion they may actually increase it.[14]

Readers may think that the CLAHRC WM Director can be rather pessimistic, even nihilistic. Not so, CLAHRC WM has recently conducted an overview (umbrella review) across 50 systematic reviews of different methods to integrate care across hospitals and communities.[15] Discharge planning with post-discharge support is highly effective. Multi-skill teams are much more effective if they include hospital outreach than if they are entirely community-based. Self-management is effective but mainly for single diseases. Case management is of minimal value. Across all intervention types, length of stay was reduced in over half, emergency admissions were reduced in half, and readmissions were reduced in nearly half. In almost no case did the intervention make any of the above outcomes worse. Costs to the service were reduced in over a third of intervention types, but the quality of evidence is poor on this point – a topic that is being addressed across all CLAHRCs. And here is the CLAHRC WM Director’s point; there are no quick wins and no silver bullets. And the solutions are not self-evident. Only by patiently trying out new things and evaluating them methodologically can things improve. It may sound self-serving, but that does not mean it is incorrect – CLAHRCs have an immense contribution to make to improve the effectiveness and cost-effectiveness of health services.

— Richard Lilford, CLAHRC WM Director

I acknowledge advice from Prof Peter Jones (University of Cambridge), Director of CLAHRC East of England, but the views expressed are entirely my own.


  1. Deaton A, Lubotsky D. Mortality, inequality and race in American cities and states. Soc Sci Med. 2003;56(6):1139-53.
  2. Chetty R HN, Katz LF. The Effects of Exposure to Better Neighbourhoods on Children: New Evidence from the Moving to Opportunity Experiment. Am Econ Rev. 2016.
  3. Matthews FE, Stephan BC, Robinson L, Jagger C, Barnes LE, Arthur A, Brayne C; Cognitive Function and Ageing Studies (CFAS) Collaboration. A two decade dementia incidence comparison from the Cognitive Function and Ageing Studies I and II. Nat Commun. 2016; 7: 11398.
  4. Matthews FE, Arthur A, Barnes LE, Bond J, Jagger C, Robinson L, Brayne C; Medical Research Council Cognitive Function and Ageing Collaboration. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. Lancet. 2013; 382(9902): 1405-12.
  5. Lilford R. Robotic hotels today – nursing homes tomorrow? NIHR CLAHRC West Midlands News Blog. March 6 2015.
  6. Lilford R. Medical Technology – Separating the Wheat from the Chaff. NIHR CLAHRC West Midlands News Blog. February 26 2016.
  7. Lilford R. Improving Diabetes Care. NIHR CLAHRC West Midlands News Blog. November 11 2016.
  8. Henderson C, Knapp M, Fernández J-L, Beecham J, Hirani SP, Cartwright M, et al. Cost effectiveness of telehealth for patients with long term conditions (Whole Systems Demonstrator telehealth questionnaire study): nested economic evaluation in a pragmatic, cluster randomised controlled trial. BMJ. 2013; 346: f1035.
  9. Tricco AC, Ivers NM, Grimshaw JM, Moher D, Turner L, Galipeau J, et al. Effectiveness of quality improvement strategies on the management of diabetes: a systematic review and meta-analysis. Lancet. 2012; 379: 2252–61.
  10. Lilford R. The Future of Medicine. NIHR CLAHRC West Midlands News Blog. October 23 2015.
  11. Lilford R. Improving Hospital Care: Not easy when budgets are pressed. NIHR CLAHRC West Midlands News Blog. January 23 2015.
  12. Laurant M, Reeves D, Hermens R, Braspenning J, Grol R, Sibbald B. Substitution of doctors by nurses in primary care. Cochrane Database Syst Rev. 2005; 2(2).
  13. Lilford R. Lay Community Health Workers. NIHR CLAHRC West Midlands News Blog. April 10 2015.
  14. Roland M, Abel G. Reducing emergency admissions: are we on the right track? BMJ. 2012; 345: e6017.
  15. Damery S, Flanagan S, Combes G. Does integrated care reduce hospital activity for patients with chronic diseases? An umbrella review of systematic reviews. BMJ Open. 2016; 6: e011952.

RCT Does Not Confirm That Moderate Intensity Physical Activity is More Effective than Health Education in Reducing Cognitive Decline in Elderly People – Pity

The attractive theory that exercise, perhaps by inducing body-wide intra-cellular autophagy, promotes the health of all tissues – including the brain – does not gain support from this RCT (total n=1,635).[1] There was almost no difference at all in cognitive decline or incidence in dementia in this 24 month study. Maybe the exercise intensity was insufficient to yield a measurable improvement, in which case the CLAHRC WM Director’s regular Spinning classes may produce some benefit after all. But he is starting to doubt it.

— Richard Lilford, CLAHRC WM Director


  1. Sink KM, Espeland MA, Castro CM, et al. Effect of a 24-Month Physical Activity Intervention vs Health Education on Cognitive Outcomes in Sedentary Older Adults: The LIFE Randomized Trial. JAMA. 2015;314(8):781-90.

Robotic hotels today – Nursing homes tomorrow?

Readers of our news blog will have seen recent posts on the dependency ratio – the notion that people in the middle of the age range produce the economic surplus needed to rear the next generation and look after the preceding generation over ever-lengthening timescales. Nowhere is the dependency ratio more adverse than in Japan – the country with the world’s greatest longevity has a fertility rate of 1.4 and a dependency ratio of 62:100.[1] One way to tackle the problem is to follow pro-natalist policies. Another is to boost productivity in the middle. What better way to do this than to substitute human labour with machines? The trouble has always been that service industries, on which advanced countries largely depend, resist mechanisation. But not anymore; the first hotel staffed by robots has opened and, unsurprisingly, it is in Nagasaki, Japan.[2]

Looking after old people is also very time intensive but it would appear that technology to ameliorate the problem is at hand. For example, battery-powered suits have been developed in Japan that function as an exoskeleton, sensing and amplifying the wearer’s muscle action, and helping carers lift patients into a bath or out of a bed. The suit can also be worn by patients themselves, to help them move around and do things without support.[3] Furthermore, a project by Sheffield Health and Social Care NHS Foundation Trust, in partnership with the University of Sheffield, is evaluating the effectiveness of a robotic baby seal, which reacts to touch and sound, to manage distress and anxiety in dementia patients.[4]

Would the CLAHRC WM Director prefer a warm-hearted human being over a robot when his time comes? Certainly, but he would prefer the robot over nothing at all.

— Richard Lilford, CLAHRC WM Director


  1. Index Mundi. Japan Demographics Profile 2014. July 2014.
  2. Cuthbertson A. Hotel staffed by humanoid robots set to open in Japan this summer. International Business Times. 9 February 2015.
  3. The Economist. Difference Engine: The Caring Robot. The Economist. 14 May 2013.
  4. Griffiths A. How Paro the robot seal is being used to help UK dementia patients. The Guardian. 8 July 2014.