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Gene expression signatures in human ageing
S6
8th Congress of the EUGMS / European Geriatric Medicine 3S (2012) S1–S32
glucometers and education of staff are essential measures to reduce hospital admissions for care home residents with hypoglycaemia. Disclosure.– No significant relationships. http://dx.doi.org/10.1016/j.eurger.2012.07.379 O016
Predictors of effectiveness of cholinesterase inhibitors in Alzheimer’s disease
certain mice models of muscle repair and beta-amyloid phagocytosis respectively. In the CCR2 mouse model of Alzheimer’s disease, replenishment of peripheral CCR2 responsive monocytes resulted in improvement of cognitive function: the emergence of CCR2 as the strongest gene expression signal with cognitive impairment in people provides an exciting focus for research on controlling Alzheimer’s pathology. This talk will summarize the promise and challenges of using expression data in epidemiological studies of aging.
J.E. De Wit ∗ , M.H. Emmelot-Vonk , H.L. Koek Geriatrics, UMC Utrecht, Utrecht, Netherlands ∗ Corresponding author.
http://dx.doi.org/10.1016/j.eurger.2012.07.381
Introduction.– Efficacy and tolerability of cholinesterase inhibitors (ChEIs) in treatment of Alzheimer’s disease (AD) are limited. Identification of good responders could prevent both overtreatment and undertreatment. The objective of this study is to determine predictors of effectiveness of ChEIs in patients with AD. Methods.– Consecutive patients diagnosed with AD (with or without cerebrovascular disease) between 2005-2010 and treated with a ChEI from a memory clinic were included. Baseline data, including Mini Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI) and Geriatric Depression Scale (GDS), and follow-up MMSEs were collected. Mann-Whitney tests were used to assess factors predictive of good response. Factors with p < 0.10 in these univariate analyses were entered into Cox multivariate regression models. Results.– The cohort comprised 112 patients with mean age 78.2 ± 7.1 years and mean baseline MMSE 22.1 ± 4.0. Lower baseline MMSE scores and higher baseline GDS scores were shown to be significant age and sex adjusted predictors of stabilisation or improvement of delta MMSE scores (difference between follow-up MMSE and baseline MMSE ≥ 0) after 12 (HR 0.94, 95%CI 0.90–0.99; P = 0.03), 18, 36 and 48 months and after 24 (HR 1.18, 95%CI 1.05–1.33; P = 0.01), 36 and 48 months, respectively. Higher NPI hallucination scores were shown to be significant age and sex adjusted predictors of a limited decline, stabilisation or improvement (delta MMSE ≥ –2) after 6 (HR 1.42, 95%CI 1.13–1.78; P < 0.01) and 18 (HR 1.34, 95%CI 1.10–1.63; P < 0.01) months. Conclusion.– These findings suggest that AD patients with lower MMSE scores, higher GDS scores and hallucinations at baseline are better responders to ChEIs. Disclosure.– No significant relationships.
Vaccination in the face of declining immunity; a problem for an aging population
http://dx.doi.org/10.1016/j.eurger.2012.07.380
O018
R. Aspinall a , S. Govind a , A. ten Bokum a , N. Kenny a , P.O. Lang a,b Cranfield Health, Cranfield University, United Kingdom b UK, Nescens Centre of Preventive Medicine, Switzerland
a
Medical social and economic reforms in the past 60 years, especially in Europe, have provided the environment for the prolonged survival of individuals within the population. The development of antibiotic therapy, mass vaccination programmes and government schemes to improve economic and social well-being means that the majority of individuals over the age of 65 are currently healthier and physically more active than their counterparts 60 years ago. More of us are reaching the age of 100 and in doing so are enjoying better facilities and greater opportunities to travel than our predecessors. This increased aging population may be one of mankind’s greatest triumphs, but it also brings with it enormous medical challenges. Protection from childhood diseases through vaccination in the past proved an important tool in preventing the spread of communicable disease but vaccines have not proved as effective in the elderly. Older individuals show an increased susceptibility to infectious agents and with new infectious agents entering the European arena, the increased population of older individuals may be at risk. We need to consider altering our vaccination strategy in future and one option would be to consider improving the immune system of the elderly. http://dx.doi.org/10.1016/j.eurger.2012.07.382 O019
Pharmagenetics and pharmacogenomics A. Pilotto a,b , D. Seripa b Geriatrics Unit Azienda ULSS 16 Padova, Italy b Gerontology and Geriatrics Research Lab, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
a
O017
Gene expression signatures in human ageing D. Melzer Epidemiology and Public Health Group, Medical School, University of Exeter, Exeter EX25DW, United Kingdom Messenger RNA (mRNA) is a key intermediate between DNA and proteins. Cells tightly regulate the amount and form of new proteins produced in response to intra- and extra-cellular signals. The amount of mRNA being produced at any point in time is a good proxy for the demand within cells for the corresponding protein. This allows us insight into how, at a cellular level, organisms react to stimuli. By profiling this expression of mRNA, we can infer the molecular mechanisms associated with aging and other phenotypes, reflecting both genetic variation and environmental exposures. Clinical tests based on gene expression signatures are already in use, notably for sub-typing and prognosis in cancer. Recent larger scale human studies of in-vivo genome wide expression (notably from the InCHIANTI aging study) have identified changes in splicing, the ‘fine tuning’ of protein sequences, as a potentially important factor in decline of cellular function with advancing age. Studies of expression associations with muscle strength and cognition have shown striking concordance with
Definitions.– The correlations between efficacy or toxicity of drugs and genetic variations at a single gene locus, commonly known as pharmacogenetics, as well as those with genetic variations at multiple genome loci, commonly known as pharmacogenomics, have been suggested as outstanding opportunities in geriatric clinical practice. Potential usefulness.– Both pharmacogenetics and pharmacogenomics have been suggested as modern approaches to improve drugs safety and efficacy in the elderly, with important consequences on the social costs of pharmacological treatments. Indeed, a pharmacogenetic approach to the therapy with several common drugs used by older patients, i.e. anticoagulants, antidepressants, acetyl-cholinesterase inhibitors for Alzheimer disease, non-steroidal-anti-inflammatory and anti-hypertensive drugs, may potentially greatly improve their safety and efficacy, avoiding a number of severe consequences such as therapeutic failures and adverse drug reactions, both serious events with a high prevalence in the elderly. Methodological limits.– Some methodological limits, however, need to be considered when we are searching for a complete
8th Congress of the EUGMS / European Geriatric Medicine 3S (2012) S1–S32
glucometers and education of staff are essential measures to reduce hospital admissions for care home residents with hypoglycaemia. Disclosure.– No significant relationships. http://dx.doi.org/10.1016/j.eurger.2012.07.379 O016
Predictors of effectiveness of cholinesterase inhibitors in Alzheimer’s disease
certain mice models of muscle repair and beta-amyloid phagocytosis respectively. In the CCR2 mouse model of Alzheimer’s disease, replenishment of peripheral CCR2 responsive monocytes resulted in improvement of cognitive function: the emergence of CCR2 as the strongest gene expression signal with cognitive impairment in people provides an exciting focus for research on controlling Alzheimer’s pathology. This talk will summarize the promise and challenges of using expression data in epidemiological studies of aging.
J.E. De Wit ∗ , M.H. Emmelot-Vonk , H.L. Koek Geriatrics, UMC Utrecht, Utrecht, Netherlands ∗ Corresponding author.
http://dx.doi.org/10.1016/j.eurger.2012.07.381
Introduction.– Efficacy and tolerability of cholinesterase inhibitors (ChEIs) in treatment of Alzheimer’s disease (AD) are limited. Identification of good responders could prevent both overtreatment and undertreatment. The objective of this study is to determine predictors of effectiveness of ChEIs in patients with AD. Methods.– Consecutive patients diagnosed with AD (with or without cerebrovascular disease) between 2005-2010 and treated with a ChEI from a memory clinic were included. Baseline data, including Mini Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI) and Geriatric Depression Scale (GDS), and follow-up MMSEs were collected. Mann-Whitney tests were used to assess factors predictive of good response. Factors with p < 0.10 in these univariate analyses were entered into Cox multivariate regression models. Results.– The cohort comprised 112 patients with mean age 78.2 ± 7.1 years and mean baseline MMSE 22.1 ± 4.0. Lower baseline MMSE scores and higher baseline GDS scores were shown to be significant age and sex adjusted predictors of stabilisation or improvement of delta MMSE scores (difference between follow-up MMSE and baseline MMSE ≥ 0) after 12 (HR 0.94, 95%CI 0.90–0.99; P = 0.03), 18, 36 and 48 months and after 24 (HR 1.18, 95%CI 1.05–1.33; P = 0.01), 36 and 48 months, respectively. Higher NPI hallucination scores were shown to be significant age and sex adjusted predictors of a limited decline, stabilisation or improvement (delta MMSE ≥ –2) after 6 (HR 1.42, 95%CI 1.13–1.78; P < 0.01) and 18 (HR 1.34, 95%CI 1.10–1.63; P < 0.01) months. Conclusion.– These findings suggest that AD patients with lower MMSE scores, higher GDS scores and hallucinations at baseline are better responders to ChEIs. Disclosure.– No significant relationships.
Vaccination in the face of declining immunity; a problem for an aging population
http://dx.doi.org/10.1016/j.eurger.2012.07.380
O018
R. Aspinall a , S. Govind a , A. ten Bokum a , N. Kenny a , P.O. Lang a,b Cranfield Health, Cranfield University, United Kingdom b UK, Nescens Centre of Preventive Medicine, Switzerland
a
Medical social and economic reforms in the past 60 years, especially in Europe, have provided the environment for the prolonged survival of individuals within the population. The development of antibiotic therapy, mass vaccination programmes and government schemes to improve economic and social well-being means that the majority of individuals over the age of 65 are currently healthier and physically more active than their counterparts 60 years ago. More of us are reaching the age of 100 and in doing so are enjoying better facilities and greater opportunities to travel than our predecessors. This increased aging population may be one of mankind’s greatest triumphs, but it also brings with it enormous medical challenges. Protection from childhood diseases through vaccination in the past proved an important tool in preventing the spread of communicable disease but vaccines have not proved as effective in the elderly. Older individuals show an increased susceptibility to infectious agents and with new infectious agents entering the European arena, the increased population of older individuals may be at risk. We need to consider altering our vaccination strategy in future and one option would be to consider improving the immune system of the elderly. http://dx.doi.org/10.1016/j.eurger.2012.07.382 O019
Pharmagenetics and pharmacogenomics A. Pilotto a,b , D. Seripa b Geriatrics Unit Azienda ULSS 16 Padova, Italy b Gerontology and Geriatrics Research Lab, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
a
O017
Gene expression signatures in human ageing D. Melzer Epidemiology and Public Health Group, Medical School, University of Exeter, Exeter EX25DW, United Kingdom Messenger RNA (mRNA) is a key intermediate between DNA and proteins. Cells tightly regulate the amount and form of new proteins produced in response to intra- and extra-cellular signals. The amount of mRNA being produced at any point in time is a good proxy for the demand within cells for the corresponding protein. This allows us insight into how, at a cellular level, organisms react to stimuli. By profiling this expression of mRNA, we can infer the molecular mechanisms associated with aging and other phenotypes, reflecting both genetic variation and environmental exposures. Clinical tests based on gene expression signatures are already in use, notably for sub-typing and prognosis in cancer. Recent larger scale human studies of in-vivo genome wide expression (notably from the InCHIANTI aging study) have identified changes in splicing, the ‘fine tuning’ of protein sequences, as a potentially important factor in decline of cellular function with advancing age. Studies of expression associations with muscle strength and cognition have shown striking concordance with
Definitions.– The correlations between efficacy or toxicity of drugs and genetic variations at a single gene locus, commonly known as pharmacogenetics, as well as those with genetic variations at multiple genome loci, commonly known as pharmacogenomics, have been suggested as outstanding opportunities in geriatric clinical practice. Potential usefulness.– Both pharmacogenetics and pharmacogenomics have been suggested as modern approaches to improve drugs safety and efficacy in the elderly, with important consequences on the social costs of pharmacological treatments. Indeed, a pharmacogenetic approach to the therapy with several common drugs used by older patients, i.e. anticoagulants, antidepressants, acetyl-cholinesterase inhibitors for Alzheimer disease, non-steroidal-anti-inflammatory and anti-hypertensive drugs, may potentially greatly improve their safety and efficacy, avoiding a number of severe consequences such as therapeutic failures and adverse drug reactions, both serious events with a high prevalence in the elderly. Methodological limits.– Some methodological limits, however, need to be considered when we are searching for a complete