Mark Fish

Bio: Mark Fish is an academic researcher from Musgrove Park Hospital. The author has contributed to research in topics: Dementia & Vascular dementia. The author has an hindex of 12, co-authored 17 publications receiving 1093 citations. Previous affiliations of Mark Fish include University of Wales.

Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis.

Abstract: Objective: To test blood and CSF neurofilament light chain (NfL) levels in relation to disease progression and survival in amyotrophic lateral sclerosis (ALS). Methods: Using an electrochemiluminescence immunoassay, NfL levels were measured in samples from 2 cohorts of patients with sporadic ALS and healthy controls, recruited in London (ALS/control, plasma: n = 103/42) and Oxford (ALS/control, serum: n = 64/36; paired CSF: n = 38/20). NfL levels in patients were measured at regular intervals for up to 3 years. Change in ALS Functional Rating Scale–Revised score was used to assess disease progression. Survival was evaluated using Cox regression and Kaplan–Meier analysis. Results: CSF, serum, and plasma NfL discriminated patients with ALS from healthy controls with high sensitivity (97%, 89%, 90%, respectively) and specificity (95%, 75%, 71%, respectively). CSF NfL was highly correlated with serum levels ( r = 0.78, p p Conclusion: Blood-derived NfL level is an easily accessible biomarker with prognostic value in ALS. The individually relatively stable levels longitudinally offer potential for NfL as a pharmacodynamic biomarker in future therapeutic trials. Classification of evidence: This report provides Class III evidence that the NfL electrochemiluminescence immunoassay accurately distinguishes patients with sporadic ALS from healthy controls.

Auditory threshold, phonologic demand, and incident dementia

Abstract: Objective: This study was undertaken to investigate the association of auditory threshold with cognitive decline and dementia. Methods: The 1,057 surviving men of the Caerphilly cohort with audiometric data at baseline were followed for 17 years for cognitive outcomes. Pure-tone unaided audiometric threshold was assessed at 0.5, 1, 2, and 4 KHz at baseline and after 9 years. Incident dementia was assessed according to DSM-IV criteria, including standard criteria for vascular dementia and for Alzheimer disease. Cognitive decline was assessed by repeat administration of a cognitive test battery. Results: Mean age-adjusted auditory threshold across both time points was associated with incident dementia and cognitive decline. After adjustment for premorbid cognitive function, the association with dementia was retained (odds ratio0.5 KHz = 2.67; 95% confidence interval, 1.38–5.18; p = 0.004). Stronger associations with cognitive decline were found for tests administered by interview than for those administered by computer. Conclusions: This study has found an association of auditory threshold with dementia and cognitive decline over a 17-year period. The mechanisms underlying this association are unclear and may include a prodromal effect of dementia on auditory threshold, an effect of auditory threshold on cognitive assessment, an effect of auditory threshold on cognitive loss, or a shared etiologic pathway between both.

Benzodiazepine use and risk of dementia: evidence from the Caerphilly Prospective Study (CaPS)

Abstract: Background Benzodiazepine use is widespread in older people, although its benefit is uncertain. Aim To investigate the long-term effect of benzodiazepine use upon dementia risk. Methods A prospective cohort of men seen on five occasions over 22 years with full medication histories, repeat measures of cognitive function and a clinical diagnosis of dementia. Results Of 1134 men with complete data, 103 (9.1%) had been taking benzodiazepines regularly at one or more phases. These men showed a marked increased incidence of dementia (OR¼3.50, 95% CI 1.57 to 7.79, p¼0.002), which persisted despite adjustment for psychological distress and other covariates. Men exposed in earlier phases showed a greater association than more recent exposure, counter to what one would expect if this was due to reverse causation, though we failed to demonstrate a doseeresponse effect with drug duration. Conclusion The taking of benzodiazepines is associated with an increased risk of dementia.

Does anxiety affect risk of dementia? Findings from the Caerphilly Prospective Study

Abstract: Objective: To examine the association of anxiety with incident dementia and cognitive impairment not dementia (CIND). Methods: We conducted a prospective study of men aged 48 to 67 years at baseline anxiety assessment; we measured cognition 17 years later. We studied 1481 men who were either eligible for examination or were known to have dementia. Trait Anxiety was assessed using the Spielberger State Trait Anxiety Inventory. Psychological distress was assessed using the 30-item general health questionnaire. Cognitive screening was followed by a clinical examination. Medical notes and death certificates of those not seen were also examined. Outcomes were CIND and Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) dementia. Results: Of 1160 men who were cognitively screened, 174 cases of CIND and 69 cases of dementia were identified. A further 21 cases of dementia were identified from medical records. After adjustment for age, vascular risk factors and premorbid cognitive function associations with higher anxiety (31st–95th centile) were for CIND odds ratio (OR) 2.31 (95% Confidence Interval (CI) = 1.20–4.44) and for dementia OR 2.37 (95% CI = 0.98–5.71). These associations were slightly stronger for nonvascular (OR = 2.45; 95% CI = 1.28–4.68) than for vascular impairment (OR = 1.94; 95% CI = 0.77–4.89). Analyses of change in cognitive performance, assessed by the Cambridge Cognitive Examination of the Elderly subscales found some evidence for decline in learning memory with higher anxiety score (bage adj = −0.291 (−0.551, −0.032), but not for any other subscale. Conclusions: Anxiety is a risk factor for CIND and dementia. The extent to which the association is independent of depression and whether or not it is causal requires further study.

Sleep disturbance and daytime sleepiness predict vascular dementia

Abstract: Background Disturbed sleep is common throughout the community and is associated with an increase in daytime sleepiness, both of which, in turn are associated with an increased risk of ischaemic vascular disease. The hypothesis that sleep disturbances are predictive of dementia, and in particular vascular dementia was tested in a large community-based cohort of older men. Methods A questionnaire on sleep disturbances was administered to 1986 men aged 55e69 years in the Caerphilly Cohort Study and 10 years later the men were examined clinically for evidence of dementia or cognitive impairment with no dementia (CIND). Findings Approximately 20% of the men reported disturbed sleep and 30% reported ‘severe’ daytime sleepiness. Ten years later 1225 men (75% of the surviving men in the cohort) were tested and 268 (22%) were found to be cognitively impaired with 93 (7.6%) showing clear evidence of dementia and the remaining 175 (14.3%) showing evidence of CIND. After adjustment for possible confounding, including cognitive function and the taking of sleeping tablets at baseline, sleep disturbances appeared to be predictive of dementia and CIND of vascular origin, while there was no suggestion of prediction of non-vascular cognitive impairment by sleep. Prediction of vascular dementia appeared to be particularly strong for daytime sleepiness, with an adjusted OR of 4.44 (95% CI 2.05 to 9.61). Further adjustments for psychological distress at baseline reduced the size of the relationships, but the ORs remain large, consistent with a direct positive effect of sleep disturbance on vascular dementia. Interpretation Sleep disturbances, and in particular severe daytime sleepiness, appear to be strongly predictive of vascular dementia, but have no predictive power for non vascular dementia.

Clinical Diagnosis of Alzheimer's Disease

Abstract: There are a number of ways in which a clinical diagnosis of dementia of the Alzheimer type can be made – the application of clinical criteria is the commonest but ancillary techniques such as neuroima