BackgroundDelirium is a common severe neuropsychiatric condition secondary to physical illness, which predominantly affects older adults in hospital. Prior to this study, the UK point prevalence of delirium was unknown. We set out to ascertain the point prevalence of delirium across UK hospitals and how this relates to adverse outcomes.MethodsWe conducted a prospective observational study across 45 UK acute care hospitals. Older adults aged 65 years and older were screened and assessed for evidence of delirium on World Delirium Awareness Day (14th March 2018). We included patients admitted within the previous 48 h, excluding critical care admissions.ResultsThe point prevalence of Diagnostic and Statistical Manual on Mental Disorders, Fifth Edition (DSM-5) delirium diagnosis was 14.7% (222/1507). Delirium presence was associated with higher Clinical Frailty Scale (CFS): CFS 4–6 (frail) (OR 4.80, CI 2.63–8.74), 7–9 (very frail) (OR 9.33, CI 4.79–18.17), compared to 1–3 (fit). However, higher CFS was associated with reduced delirium recognition (7–9 compared to 1–3; OR 0.16, CI 0.04–0.77). In multivariable analyses, delirium was associated with increased length of stay (+ 3.45 days, CI 1.75–5.07) and increased mortality (OR 2.43, CI 1.44–4.09) at 1 month. Screening for delirium was associated with an increased chance of recognition (OR 5.47, CI 2.67–11.21).ConclusionsDelirium is prevalent in older adults in UK hospitals but remains under-recognised. Frailty is strongly associated with the development of delirium, but delirium is less likely to be recognised in frail patients. The presence of delirium is associated with increased mortality and length of stay at one month. A national programme to increase screening has the potential to improve recognition.
Background and purpose The prevalence and duration of non‐motor symptoms (NMS) in prodromal Parkinson's disease (PD) has not been extensively studied. The aim of this study was to determine the prevalence and duration of prodromal NMS (pNMS) in a cohort of patients with recently diagnosed PD. Methods We evaluated the prevalence and duration of pNMS in patients with early PD ( n = 154). NMS were screened for using the Non‐Motor Symptom Questionnaire (NMSQuest). We subtracted the duration of the presence of each individual NMS reported from the duration of the earliest motor symptom. NMS whose duration preceded the duration of motor symptoms were considered a pNMS. Individual pNMS were then grouped into relevant pNMS clusters based on the NMSQuest domains. Motor subtypes were defined as tremor dominant, postural instability gait difficulty (PIGD) and indeterminate type according to the Movement Disorder Society Unified Parkinson's Disease Rating Scale revision. Results Prodromal NMS were experienced by 90.3% of patients with PD and the median number experienced was 4 (interquartile range, 2–7). A gender difference existed in the pNMS experienced, with males reporting more sexual dysfunction, forgetfulness and dream re‐enactment, whereas females reported more unexplained weight change and anxiety. There was a significant association between any prodromal gastrointestinal symptoms [odds ratio (OR), 2.30; 95% confidence interval (CI), 1.08–4.89, P = 0.03] and urinary symptoms (OR, 2.54; 95% CI, 1.19–5.35, P = 0.016) and the PIGD phenotype. Further analysis revealed that total pNMS were not significantly associated with the PIGD phenotype (OR, 1.10; 95% CI, 0.99–1.21, P = 0.068). Conclusions Prodromal NMS are common and a gender difference in pNMS experienced in prodromal PD may exist. The PIGD phenotype had a higher prevalence of prodromal gastrointestinal and urinary tract symptoms.
ObjectiveAlthough not typical of Parkinson’s disease (PD), caudate dopaminergic dysfunction can occur in early stages of the disease. However, its frequency and longitudinal implications in large cohorts of recently diagnosed patients remain to be established. We investigated the occurrence of caudate dopaminergic dysfunction in the very early phases of PD (<2 years from diagnosis) using 123I-FP-CIT single photon emission CT and determined whether it was associated with the presence or subsequent development of cognitive impairment, depression, sleep and gait problems.MethodsPatients with PD and healthy controls were identified from the Parkinson’s Progression Markers Initiative (PPMI) database. We defined a clinically significant caudate dysfunction as 123I-FP-CIT binding <–2 SDs compared with the controls’ mean and categorised three groups accordingly (no reduction, unilateral reduction, bilateral reduction). All statistical analyses were adjusted for mean putamen binding.ResultsAt baseline, 51.6% of 397 patients had normal caudate dopamine transporter binding, 26.0% had unilateral caudate involvement, 22.4% had bilaterally impaired caudate.Compared with those with a baseline normal caudate function, at the4-year follow-up patients with a baseline bilateral caudate involvement showed a higher frequency of cognitive impairment (p<0.001) and depression (p<0.001), and worse cognitive (p<0.001), depression (<0.05) and gait (<0.001) ratings. Significant caudate involvement was observed in 83.9% of the population after 4 years (unilateral 22.5%, bilateral 61.4%).ConclusionsEarly significant caudate dopaminergic denervation was found in half of the cases in the PPMI series. Baseline bilateral caudate involvement was associated with increased risk of developing cognitive impairment, depression and gait problems over the next 4 years.
Objectives: To investigate using quantitative EEG the (1) differences between patients with mild cognitive impairment with Lewy bodies (MCI-LB) and MCI with Alzheimer's disease (MCI-AD) and (2) its utility as a potential biomarker for early differential diagnosis. Methods: We analyzed eyes-closed, resting-state, high-density EEG data from highly phenotyped participants (39 MCI-LB, 36 MCI-AD, and 31 healthy controls). EEG measures included spectral power in different frequency bands (delta, theta, pre-alpha, alpha, and beta), theta/alpha ratio, dominant frequency, and dominant frequency variability. Receiver operating characteristic (ROC) analyses were performed to assess diagnostic accuracy. Results: There was a shift in power from beta and alpha frequency bands towards slower frequencies in the prealpha and theta range in MCI-LB compared to healthy controls. Additionally, the dominant frequency was slower in MCI-LB compared to controls. We found significantly increased pre-alpha power, decreased beta power, and slower dominant frequency in MCI-LB compared to MCI-AD. EEG abnormalities were more apparent in MCI-LB cases with more diagnostic features. There were no significant differences between MCI-AD and controls. In the ROC analysis to distinguish MCI-LB from MCI-AD, beta power and dominant frequency showed the highest area under the curve values of 0.71 and 0.70, respectively. While specificity was high for some measures (up to 0.97 for alpha power and 0.94 for theta/alpha ratio), sensitivity was generally much lower. Conclusions: Early EEG slowing is a specific feature of MCI-LB compared to MCI-AD. However, there is an overlap between the two MCI groups which makes it difficult to distinguish between them based on EEG alone.
Dementia with Lewy bodies and Alzheimer’s disease show early degeneration of the cholinergic nucleus basalis of Meynert. However, how white matter projections between the nucleus basalis of Meynert and the cortex are altered in neurodegenerative disease is unknown. Tractography of white matter pathways originating from the nucleus basalis of Meynert was performed using diffusion-weighted imaging in 46 Alzheimer’s disease dementia, 48 dementia with Lewy bodies, 35 mild cognitive impairment with Alzheimer’s disease, 38 mild cognitive impairment with Lewy bodies, and 71 controls. Mean diffusivity of the resulting pathways was compared between groups and related to cognition, attention, functional EEG changes, and dementia conversion in the mild cognitive impairment groups. We successfully tracked a medial and a lateral pathway from the nucleus basalis of Meynert. Mean diffusivity of the lateral pathway was higher in both dementia and mild cognitive impairment groups than controls (all P < 0.03). In the patient groups, increased mean diffusivity of this pathway was related to more impaired global cognition (β=-0.22, P = 0.06) and worse performance on an attention task (β = 0.30, P = 0.03). In patients with mild cognitive impairment, loss of integrity of both nucleus basalis of Meynert pathways was associated with increased risk of dementia progression (hazard ratio [95% confidence interval], medial pathway: 2.51 [1.24–5.09]; lateral pathway: 2.54 [1.24–5.19]). Nucleus basalis of Meynert volume was reduced in all clinical groups compared to controls (all P < 0.001), but contributed less strongly to cognitive impairment and was not associated with attention or dementia conversion. EEG slowing in the patient groups as assessed by a decrease in dominant frequency was associated with smaller nucleus basalis of Meynert volumes (β = 0.22, P = 0.02) and increased mean diffusivity of the lateral pathway (β=-0.47, P = 0.003). We show that degeneration of the cholinergic nucleus basalis of Meynert in Alzheimer’s disease and dementia with Lewy bodies is accompanied by an early reduction in integrity of white matter projections that originate from this structure. This is more strongly associated with cognition and attention than the volume of the nucleus basalis of Meynert itself and might be an early indicator of increased risk of dementia conversion in people with mild cognitive impairment.
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