Asking the Big Questions in Dublin’s Fair City – Part 2

Mary Ni Lochlainn is an Academic Clinical Fellow in Geriatric Medicine. She works at King’s College Hospital NHS Foundation Trust.

In the world of Alzheimer’s research we heard from Professor Michael Rowan, who focused on amyloid and ageing. Sleep and mood disorders can pre-date dementia diagnoses, and we see circadian rhythm disturbances in Alzheimer’s disease (AD). Is there a window of opportunity here for preventative interventions? Alzheimer’s is a disease of abnormal protein aggregation – both amyloid and tau. Protein clearance tends to happen at night. Can we draw connections here? Prof Rowan explained that a recent New England Journal of Medicine paper showed 30% of patients didn’t have any amyloid even though they had been diagnosed with AD and enrolled in a trial. So what does this mean? Do these patients have another dementia? It cannot be denied that a blood or cerebrospinal fluid test would be very helpful in this diagnostic process.

Were you aware of the role of microglia in phagocytosis aka mopping up protein? Professor Marina Lynch expertly informed us that these microglia can actually be assessed using PET scanning and may well be a target for AD in that abnormal protein accumulation that Prof Rowan was discussing. As for the peripheral biomarkers of AD that would help us with diagnosis; Prof Lynch put forward Il-1beta, highlighted in a meta-analysis of biomarkers of AD. Plenty more work to be done in this area.

Moving onto older surgical patients, plastic surgeon Mr. Odhran Shelley gave us all something to think about in the context of surgical scoring systems. For example, the Mangled Extremity Severity Score (MESS) gives 1 point for being over 30, and 2 points for being over 40. A score of over 4 suggests amputation of the limb is likely! There is often a mortality increase with higher scores. Age is included in many surgical scores and as you can see, it’s often not particularly old age either. What does that mean for geriatricians? Well these scores are usually based on large cohorts who excluded older adults or those with frailty/co-morbidities. As such they really are not representative of our population. To be taken with a pinch of salt.

Why don’t vaccines work as well in older adults? Prof Ed Lavelle is working on this. It was also raised that antimicrobial resistance is increasingly looking like our next biggest health crisis, following in the footsteps of issues like AIDS or Ebola virus. Why is this not getting more attention? Older people will be disproportionately affected and one hopes there is not some inherent ageism at play here.

Thinking about ageing mechanisms, it can be useful to look at models of accelerated ageing such as progeria, or those with chronic diseases like HIV or rheumatoid arthritis. Indeed homeless people have been reported to have COPD, low impact fractures, and cognitive impairment at much younger ages than the rest of the population. Dr. Cliona Ni Cheallaigh presented the work of a recent project showing that local homeless people in Dublin had worse MOCA scores and falls rate than the oldest cohort within TILDA! Mental health patients also show signs of accelerated ageing. Does psychosocial stress cause inflammation? TILDA data does show that education level is correlated with CRP level. And we know that higher CRP levels are associated with frailty. Lots more exciting work to be done in these areas.

Closing out the conference we had the impressive Dr. Anne Curtis’ talk on the body clock. We know older people sleep less, and indeed that circadian rhythm disturbances are associated with developing cognitive impairment. It was quite staggering to hear that 87% of our time now is spent indoors – typically in dim light, confusing our suprachiasmatic nucleus. Furthermore the blue light emitted from smartphones has been shown to inhibit melatonin release, delaying sleep. We are yet to truly appreciate what the effects of these changes in society have on our health. Dr Curtis wondered aloud whether we should be doing various tests within the research setting 12 hours apart, as well as at the usual time points in studies. More food for thought.

The event was so engaging I really could have written a blog on each speaker’s presentation and the talks given by those not mentioned here were also very thought-provoking. The organisers at MISA argue that a deeper understanding of the biology associated with ageing related-disease offers the opportunity to develop diagnostics, therapeutics, medical devices, food for health and technology to support independent living. I certainly agree.

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