ORCID Profile
0000-0002-4516-0337
Current Organisations
Ohio University
,
University of Victoria
,
The University of Edinburgh
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Publisher: Oxford University Press (OUP)
Date: 09-08-2012
DOI: 10.1093/BRAIN/AWS190
Publisher: Oxford University Press (OUP)
Date: 22-01-2015
DOI: 10.1093/IJE/DYU277
Publisher: Cold Spring Harbor Laboratory
Date: 04-09-2022
DOI: 10.1101/2022.09.04.22279576
Abstract: Anticholinergic drugs block muscarinic receptors in the body. They are commonly prescribed for a variety of indications and their use has previously been associated with dementia and cognitive decline. UK Biobank participants with linked health-care records (n=163,043, aged 40-71 at baseline), for about 17,000 of which MRI data was available, we calculated the total anticholinergic drug burden according to 15 different anticholinergic scales and due to different classes of drugs. We then used linear regression to explore the associations between anticholinergic burden and various measures of cognition and structural MRI, including general cognitive ability, 9 separate cognitive domains, brain atrophy, volumes of 68 cortical and 14 subcortical areas, and fractional anisotropy and median diffusivity of 25 white-matter tracts. Anticholinergic burden was modestly associated with poorer cognition across most anticholinergic scales and cognitive tests (7/9 FDR-adjusted significant associations, standardised betas (β) range: −0.039, −0.003). When using the anticholinergic scale exhibiting the strongest association with cognitive functions, anticholinergic burden due to only some classes of drugs exhibited negative associations with cognitive function, with β-lactam antibiotics (β=-0.035, p FDR .001) and opioids (β=-0.026, p FDR .001) exhibiting the strongest effects. Anticholinergic burden was not associated with any measure of brain macro- or microstructure (p FDR .08). Anticholinergic burden is weakly associated with poorer cognition, but there is little evidence for associations with brain structure. Future studies might focus more broadly on polypharmacy or more narrowly on distinct drug classes, instead of using purported anticholinergic action to study the effects of drugs on cognitive ability.
Publisher: Cold Spring Harbor Laboratory
Date: 16-07-2023
DOI: 10.1101/2023.07.14.23292648
Abstract: PREVENT is a multi-centre prospective cohort study in the UK and Ireland that aims to examine mid-life risk factors for dementia, identify and describe the earliest indices of disease development. The PREVENT dementia programme is one of the original epidemiological initiatives targeting midlife as a critical window for intervention in neurodegenerative conditions. This paper provides an overview of the study protocol and presents the first summary results from the initial baseline data to describe the cohort. Participants in the PREVENT cohort provide demographic data, biological s les (blood, saliva, urine and optional cerebrospinal fluid), lifestyle and psychological questionnaires, undergo a comprehensive cognitive test battery, and are imaged using multi-modal 3T magnetic resonance imaging (MRI) scanning, with both structural and functional sequences. The PREVENT cohort governance structure is described, which includes a steering committee, a scientific advisory board and core patient and public involvement groups. A number of sub-studies which supplement the main PREVENT cohort are also described. The PREVENT cohort baseline data includes 700 participants recruited between 2014 and 2020 across five sites in the UK and Ireland (Cambridge, Dublin, Edinburgh, London and Oxford). At baseline, participants had a mean age of 51.2 years (range 40-59, SD ±5.47), with the majority female (n=433, 61.9%). There was a near equal distribution of participants with and without a parental history of dementia (51.4% vs 48.6%) and a relatively high prevalence of APOE⍰4 carriers (n=264, 38.0%). Participants were highly educated (16.7 ± 3.44 years of education), were mainly of European Ancestry (n=672, 95.9%) and were cognitively healthy as measured by the Addenbrookes Cognitive Examination-III (ACE-III) (Total score 95.6 ±4.06). Mean white matter hyperintensity (WMH) volume at recruitment was 2.26 ± 2.77 ml (median = 1.39ml), with hippoc al volume 8.15 ± 0.79ml. There was good representation of known dementia risk factors in the cohort. The PREVENT cohort offers a novel dataset to explore midlife risk factors and early signs of neurodegenerative disease. Data are available open access at no cost via the Alzheimer’s Disease Data Initiative (ADDI) platform and Dementia Platforms UK (DPUK) platform pending approval of the data access request from the PREVENT steering group committee.
Publisher: American Medical Association (AMA)
Date: 03-2017
Publisher: Oxford University Press (OUP)
Date: 13-10-2008
Abstract: the investigation of cognitive decline in the older population has been h ered by analytical considerations. Most studies of older people over prolonged periods suffer from loss to follow-up, yet this has seldom been investigated fully to date. Such considerations limit our understanding of how basic variables such as education can affect cognitive trajectories. we examined cognitive trajectories in a population-based cohort study in Cambridge, UK, of people aged 75 and over in whom multiple interviews were conducted over time. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Socio-demographic variables were measured, including educational level and social class. An age-based quadratic latent growth model was fitted to cognitive scores. The effect of socio-demographic variables was examined on all latent variables and the probability of death and dropout. at baseline, age, education, social class and mobility were associated with cognitive performance. Education and social class were not related to decline or its rate of change. In contrast, poor mobility was associated with lower cognitive performance, increased cognitive decline and increased rate of change of cognitive decline. Gender, age, mobility and cognitive ability predicted death and dropout contrary to much of the current literature, education was not related to rate of cognitive decline or change in this rate as measured by MMSE. Higher levels of education do not appear to protect against cognitive decline, though if the MMSE is used in the diagnostic process, in iduals with less education may be diagnosed as having dementia somewhat earlier.
Publisher: Wiley
Date: 19-09-2022
DOI: 10.1111/BCP.15045
Abstract: The use of prescription drugs with anticholinergic properties has been associated with multiple negative health outcomes in older people. Moreover, recent evidence suggests that associated adverse effects may occur even decades after stopping anticholinergic use. Despite the implicated importance of examining longitudinal patterns of anticholinergic prescribing for different age groups, few such data are available. We performed an age-period-cohort (APC) analysis to study trends in an aggregate measure of anticholinergic burden between the years 1990 and 2015, utilising data from >220 000 UK Biobank participants with linked prescription data from primary care. Anticholinergic burden in the s le increased up to 9-fold over 25 years and was observed for both period and age effects across most classes of drugs. The greatest increase was seen in the prescribing of antidepressants. Female sex, lower education and greater deprivation were associated with greater anticholinergic burden. The increase in anticholinergic prescribing is mostly due to an increase in polypharmacy and is attributable to both ageing of participants and period-related changes in prescribing practices. Research is needed to clarify the implications of rising anticholinergic use for public health and to contextualise this rise in light of other relevant prescribing practices.
Publisher: Oxford University Press (OUP)
Date: 17-10-2013
Publisher: Springer Science and Business Media LLC
Date: 05-10-2017
Publisher: Oxford University Press (OUP)
Date: 07-07-2014
Publisher: Oxford University Press (OUP)
Date: 14-02-2017
Publisher: Oxford University Press (OUP)
Date: 22-07-2017
Abstract: The oldest-old (aged ≥85 years) are the fastest growing age group, with the highest risk of cognitive impairment and dementia. This study investigated whether cognitive reserve applies to the oldest-old. This has implications for cognitive interventions in this age group. Baseline and 5-year follow-up data from the Newcastle 85+ Study were used (N = 845, mean age = 85.5, 38% male). A Cognitive Reserve Index (CRI) was created, including: education, social class, marital status, engagement in mental activities, social participation, and physical activity. Global (Mini-Mental State Examination) and domain specific (Cognitive Drug Research Battery subtests assessing memory, attention, and speed) cognitive functions were assessed. Dementia diagnosis was determined by health records. Logistic regression analysis examined the association between CRI scores and incident dementia. Mixed effects models investigated baseline and longitudinal associations between the CRI scores and cognitive function. Analyses controlled for sex, age, depression, and cardiovascular disease history. Higher reserve associated with better cognitive performance on all baseline measures, but not 5-year rate of change. The CRI associated with prevalent, but not incident dementia. In the oldest-old, higher reserve associated with better baseline global and domain-specific cognitive function and reduced risk of prevalent dementia but not cognitive decline or incident dementia. Increasing reserve could promote cognitive function in the oldest-old. The results suggest there would be little impact on trajectories, but replication is needed. Development of preventative strategies would benefit from identifying the role of each factor in building reserve and why rate of change is not affected.
Publisher: Elsevier BV
Date: 12-2013
Publisher: Cold Spring Harbor Laboratory
Date: 18-10-2020
DOI: 10.1101/2020.10.16.20213884
Abstract: The use of prescription drugs with anticholinergic properties has been associated with multiple negative health outcomes in older people. Moreover, recent evidence suggests that associated adverse effects may occur even decades after stopping anticholinergic use. Despite the implicated importance of examining longitudinal patterns of anticholinergic prescribing for different age groups, few such data are available. We performed an age-period-cohort analysis to study trends in anticholinergic burden between the years 1990 and 2015 utilising data from ,000 UK Biobank participants with linked prescription data from primary care. Anticholinergic burden in the s le increased between three- and nine-fold over 25 years and was significant for both period/cohort- and age-effects across all models. When adjusted for total number of prescriptions, the effect of age reversed. Anticholinergic burden was also associated with various lifestyle- and demographic factors. The increase in anticholinergic prescribing is mostly due to an increase in polypharmacy and is attributable to both ageing of participants, as well as period/cohort-related changes in prescribing practices. There is evidence for deprescribing of anticholinergic medications in older age. Further research is needed to clarify the implications of rising anticholinergic use for public health and to contextualise this rise in light of other relevant prescribing practices.
Publisher: Cambridge University Press (CUP)
Date: 12-11-2009
DOI: 10.1017/S1041610209990937
Abstract: Background: Cognitive decline in old age varies among in iduals. The identification of groups of in iduals with similar patterns of cognitive change over time may improve our ability to see whether the effect of risk factors is consistent across groups. Methods: Whilst accounting for the missing data, growth mixture models (GMM) were fitted to data from four interview waves of a population-based longitudinal study of aging, the Cambridge City over 75 Cohort Study (CC75C). At all interviews global cognition was assessed using the Mini-mental State Examination (MMSE). Results: Three patterns were identified: a slow decline with age from a baseline of cognitive ability (41% of s le), an accelerating decline from a baseline of cognitive impairment (54% of s le) and a steep constant decline also from a baseline of cognitive impairment (5% of s le). Lower cognitive scores in those with less education were seen at baseline for the first two groups. Only in those with good performance and steady decline was the effect of education strong, with an increased rate of decline associated with poor education. Good mobility was associated with higher initial score in the group with accelerating change but not with rate of decline. Conclusion: Using these analytical methods it is possible to detect different patterns of cognitive change with age. In this investigation the effect of education differs with group. To understand the relationship of potential risk factors for cognitive decline, careful attention to dropout and appropriate analytical methods, in addition to long-term detailed studies of the population points, are required.
Publisher: Elsevier BV
Date: 10-2017
Publisher: Wiley
Date: 13-12-2019
Publisher: Cold Spring Harbor Laboratory
Date: 06-09-2021
DOI: 10.1101/2021.09.03.21263066
Abstract: Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4,058 plasma proteins are performed (N=774), identifying 2,928 CpG-protein associations after adjustment for multiple testing. These were independent of known genetic protein quantitative trait loci (pQTLs) and common lifestyle effects. Phenome-wide association studies of each protein are then performed in relation to 15 neurological traits (N=1,065), identifying 405 associations between the levels of 191 proteins and cognitive scores, brain imaging measures or APOE e4 status. We uncover 35 previously unreported DNA methylation signatures for 17 protein markers of brain health. The epigenetic and proteomic markers we identify are pertinent to understanding and stratifying brain health.
Publisher: Wiley
Date: 09-12-2010
DOI: 10.1002/GPS.2566
Abstract: To explore whether it is possible to detect decline in global scores of cognitive function in the proximity of death whilst simultaneously investigating potential risk profiles. Using the Mini Mental State Examination in a population study of the oldest old in which 99% of participants have died, a linear and quadratic time-to-death repeated measures random effects models were used to detect decline and potential factors which might indicate in idual variation. Decline and acceleration of this decline were detectable in the period before death. Some between person variation was detected in this pattern, which included differences in cognitive performance by age at death (-0.2 (SE = 0.02)), sex (-1.2 (SE = 0.2)), initial cognitive impairment (-7.5 (SE = 0.2)) and mobility (-0.6 (SE = 0.2)), in rate of decline by age at death (-0.04 (SE = 0.005)), sex (-0.1 (SE = 0.06)), initial cognitive impairment (-0.3 (SE = 0.07)) and mobility (-0.1 (SE = 0.05)) and differences in change in rate of decline by sex (-0.008 (SE = 0.004)), initial cognitive impairment (-0.02 (SE = 0.04)) and mobility (-0.01 (SE = 0.003)). Using an extension of existing methods for exploring terminal decline, the phenomenon of decline in global cognition measures in the proximity of death was clearly detected as well as potential variables which could influence that pattern. Further work is required to explore whether similar methods can be used to detect the onset of the acceleration of this decline in each in idual together with the potential to identify in idual level factors that can allow clinicians to distinguish between the normal and preterminal phases of change in extreme old age.
Publisher: Wiley
Date: 27-11-2010
DOI: 10.1002/GPS.2413
Abstract: Investigate the impact of the changes in eligibility within England and Wales (E&W) for prescription within the UK National Health Service for treatment of Alzheimer's disease (AD). A population-based study in England and Wales with 13,004 in iduals measured with MMSE at baseline was used to examine the distributions of in iduals within eligibility criteria. Information obtained from informants enabled classification of the study defined dementia cases to ICD10 diagnosis of subtype (AD, dementia with vascular risk, both or other). Fifty six per cent of dementia patients (representing 323,000 in iduals in E&W) fall into the new MMSE criteria band. A further 120,000, 20% of dementia patients, are estimated to have disease that is considered too mild for treatment. Further examination of type of dementia showed that those with mixed AD and vascular dementia had similar proportions of dementia cases within the treatable MMSE group as the subgroup with AD alone, though with mixed disease in iduals more often score below the lower threshold. There is substantial instability in the eligibility groupings over a short time period. The population impact of new NICE criteria of excluding high MMSE scores is to exclude one in five in iduals with AD and a further one in ten of those with a mixed disease. Changing the guidance has almost balanced the loss of treatment for the high MMSE group (13%) with the introduction of treatment for those scoring 10/11 (11%).
Publisher: Wiley
Date: 09-2015
Publisher: Springer Science and Business Media LLC
Date: 16-05-2008
Publisher: Cold Spring Harbor Laboratory
Date: 05-08-2021
DOI: 10.1101/2021.08.04.21261330
Abstract: Previous studies on the association between the long-term use of anticholinergic drugs and dementia report heterogenous results. This variability could be due to, among other factors, different anticholinergic scales used, and differential effects of distinct classes of anticholinergic drugs. Here, we use 171,775 participants of UK Biobank with linked GP prescription records to calculate the cumulative annual anticholinergic burden (ACB) and ascertain dementia diagnoses through GP- and inpatient records. We then compare 13 anticholinergic scales and anticholinergic burden (ACB) due to different classes of drugs in their association with dementia. We find dementia to be more strongly predicted by ACB than by polypharmacy across most anticholinergic scales (standardised ORs range: 1.027-1.125). Furthermore, not only the baseline ACB, but the slope of the longitudinal trajectory of ACB (HR=1.094 95% CI: 1.068-1.119) is predictive of dementia. However, the association between ACB and dementia holds only for some classes of drugs – especially antidepressants, antiepileptics, and high-ceiling antidiuretics. Moreover, we do not find a clear relationship between reported anticholinergic potency and dementia risk. The heterogeneity in findings on the association between ACB and dementia may in part be due to different effects for different classes of drugs. Future studies should establish such differences in more detail and further examine the practicality of using a general measure of anticholinergic potency as it relates to the risk of dementia.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Graciela Muniz Terrera.