Sustained attention in mild cognitive impairment with Lewy bodies and Alzheimer's disease.

OBJECTIVE: Attentional impairments are common in dementia with Lewy bodies and its prodromal stage of mild cognitive impairment (MCI) with Lewy bodies (MCI-LB). People with MCI may be capable of compensating for subtle attentional deficits in most circumstances, and so these may present as occasional lapses of attention. We aimed to assess the utility of a continuous performance task (CPT), which requires sustained attention for several minutes, for measuring attentional performance in MCI-LB in comparison to Alzheimer's disease (MCI-AD), and any performance deficits which emerged with sustained effort. METHOD: We included longitudinal data on a CPT sustained attention task for 89 participants with MCI-LB or MCI-AD and 31 healthy controls, estimating ex-Gaussian response time parameters, omission and commission errors. Performance trajectories were estimated both cross-sectionally (intra-task progress from start to end) and longitudinally (change in performance over years). RESULTS: While response times in successful trials were broadly similar, with slight slowing associated with clinical parkinsonism, those with MCI-LB made considerably more errors. Omission errors were more common throughout the task in MCI-LB than MCI-AD (OR 2.3, 95% CI: 1.1-4.7), while commission errors became more common after several minutes of sustained attention. Within MCI-LB, omission errors were more common in those with clinical parkinsonism (OR 1.9, 95% CI: 1.3-2.9) or cognitive fluctuations (OR 4.3, 95% CI: 2.2-8.8). CONCLUSIONS: Sustained attention deficits in MCI-LB may emerge in the form of attentional lapses leading to omissions, and a breakdown in inhibitory control leading to commission errors.

Blood pressure and heart rate responses to orthostatic challenge and Valsalva manoeuvre in mild cognitive impairment with Lewy bodies.

OBJECTIVES: Orthostatic hypotension is a common feature of normal ageing, and age-related neurodegenerative diseases, in particular the synucleinopathies including dementia with Lewy bodies. Orthostatic hypotension and other abnormal cardiovascular responses may be early markers of Lewy body disease. We aimed to assess whether abnormal blood pressure and heart rate responses to orthostatic challenge and Valsalva manoeuvre would be more common in mild cognitive impairment with Lewy bodies (MCI-LB) than MCI due to Alzheimer's disease (MCI-AD). METHODS: MCI patients (n = 89) underwent longitudinal clinical assessment with differential classification of probable MCI-LB, possible MCI-LB, or MCI-AD, with objective autonomic function testing at baseline. Blood pressure and heart rate responses to active stand and Valsalva manoeuvre were calculated from beat-to-beat cardiovascular data, with abnormalities defined by current criteria, and age-adjusted group differences estimated with logistic models. RESULTS: Orthostatic hypotension and abnormal heart rate response to orthostatic challenge were not more common in probable MCI-LB than MCI-AD. Heart rate abnormalities were likewise not more common in response to Valsalva manoeuvre in probable MCI-LB. An abnormal blood pressure response to Valsalva (delayed return to baseline/absence of overshoot after release of strain) was more common in probable MCI-LB than MCI-AD. In secondary analyses, magnitude of blood pressure drop after active stand and 10-s after release of Valsalva strain were weakly correlated with cardiac sympathetic denervation. CONCLUSIONS: Probable MCI-LB may feature abnormal blood pressure response to Valsalva, but orthostatic hypotension is not a clear distinguishing feature from MCI-AD.

Assessment of autonomic symptoms may assist with early identification of mild cognitive impairment with Lewy bodies.

OBJECTIVES: Autonomic symptoms are a common feature of the synucleinopathies, and may be a distinguishing feature of prodromal Lewy body disease. We aimed to assess whether the cognitive prodrome of dementia with Lewy bodies, mild cognitive impairment (MCI) with Lewy bodies (MCI-LB), would have more severe reported autonomic symptoms than cognitively healthy older adults, with MCI due to Alzheimer's disease (MCI-AD) also included for comparison. We also aimed to assess the utility of an autonomic symptom scale in differentiating MCI-LB from MCI-AD. METHODS: Ninety-three individuals with MCI and 33 healthy controls were assessed with the Composite Autonomic Symptom Score 31-item scale (COMPASS). Mild cognitive impairment patients also underwent detailed clinical assessment and differential classification of MCI-AD or MCI-LB according to current consensus criteria. Differences in overall COMPASS score and individual symptom sub-scales were assessed, controlling for age. RESULTS: Age-adjusted severity of overall autonomic symptomatology was greater in MCI-LB (Ratio = 2.01, 95% CI: 1.37-2.96), with higher orthostatic intolerance and urinary symptom severity than controls, and greater risk of gastrointestinal and secretomotor symptoms. MCI-AD did not have significantly higher autonomic symptom severity than controls overall. A cut-off of 4/5 on the COMPASS was sensitive to MCI-LB (92%) but not specific to this (42% specificity vs. MCI-AD and 52% vs. healthy controls). CONCLUSIONS: Mild cognitive impairment with Lewy bodies had greater autonomic symptom severity than normal ageing and MCI-AD, but such autonomic symptoms are not a specific finding. The COMPASS-31 may therefore have value as a sensitive screening test for early-stage Lewy body disease.

Progression to Dementia in Mild Cognitive Impairment With Lewy Bodies or Alzheimer Disease.

OBJECTIVE: To determine whether mild cognitive impairment with Lewy bodies or Alzheimer's disease differ in their rates of clinical progression to dementia, we undertook longitudinal observation of mild cognitive impairment cases with detailed clinical assessment of Lewy body diagnostic characteristics. METHODS: Two prospective longitudinal cohorts combining to 111 individuals aged 60 years or older with mild cognitive impairment were assessed annually to track cognitive and clinical progression, including the presence or absence of core clinical features and proposed biomarkers of dementia with Lewy bodies. Multi-state modelling was used to assess the associations of diagnostic characteristics of dementia with Lewy bodies with clinical progression from mild cognitive impairment to dementia, with death as a competing outcome. RESULTS: After a mean follow-up of 2.2 years (range = 1-6.7 years), 38/111 (34%) of the participants progressed to dementia: 10 with AD, 3 with possible dementia with Lewy bodies and 25 with probable dementia with Lewy bodies. The presence of any Lewy body disease characteristic was associated with an increased hazard of transition to dementia; this risk further increased as more diagnostic characteristics were observed (Hazard ratio = 1.33 per characteristic, 95% CI: 1.11-1.60), and was especially high for those experiencing complex visual hallucinations (Hazard ratio = 1.98, 95% CI: 0.92-4.29) or cognitive fluctuations (Hazard ratio = 3.99, 95% CI: 2.03-7.84). CONCLUSIONS: Diagnostic characteristics of Lewy body disease are associated with an increased risk of transition from mild cognitive impairment to dementia.

Clinical diagnosis of Lewy body dementia.

BACKGROUND: Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series. AIMS: This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences. METHOD: We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions. RESULTS: The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs. CONCLUSIONS: Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.

Clinical prevalence of Lewy body dementia.

BACKGROUND: The prevalence of dementia with Lewy bodies (DLB) and dementia in Parkinson's disease (PDD) in routine clinical practice is unclear. Prevalence rates observed in clinical and population-based cohorts and neuropathological studies vary greatly. Small sample sizes and methodological factors in these studies limit generalisability to clinical practice. METHODS: We investigated prevalence in a case series across nine secondary care services over an 18-month period, to determine how commonly DLB and PDD cases are diagnosed and reviewed within two regions of the UK. RESULTS: Patients with DLB comprised 4.6% (95% CI 4.0-5.2%) of all dementia cases. DLB was represented in a significantly higher proportion of dementia cases in services in the North East (5.6%) than those in East Anglia (3.3%; χ2 = 13.6, p < 0.01). DLB prevalence in individual services ranged from 2.4 to 5.9%. PDD comprised 9.7% (95% CI 8.3-11.1%) of Parkinson's disease cases. No significant variation in PDD prevalence was observed between regions or between services. CONCLUSIONS: We found that the frequency of clinical diagnosis of DLB varied between geographical regions in the UK, and that the prevalence of both DLB and PDD was much lower than would be expected in this case series, suggesting considerable under-diagnosis of both disorders. The significant variation in DLB diagnostic rates between these two regions may reflect true differences in disease prevalence, but more likely differences in diagnostic practice. The systematic introduction of more standardised diagnostic practice could improve the rates of diagnosis of both conditions.

Improving retention of very old participants in longitudinal research: experiences from the Newcastle 85+ study.

BACKGROUND: People aged 85 and over are often excluded from research on the grounds of being difficult to recruit and problematic to retain. The Newcastle 85+ study successfully recruited a cohort of 854 85-year-olds to detailed health assessment at baseline and followed them up over 3 phases spanning 5 years. This paper describes the effectiveness of its retention strategies. METHODS: Primary retention strategies involved meticulous management of contact information and active maintenance of contact with participants between research visits and between phases of the study. For statistical analysis, data on post-inclusion attrition over the 3 follow-up phases was separated into 'death' and 'withdrawal' categories, with sub-categories 'health' and 'non-health' reasons created for 'withdrawal'. Multinomial logistic regression was used to determine if particular socio-demographic and health characteristics were associated with post-inclusion attrition due to withdrawal at each of the 3 phase-to-phase transition points. RESULTS: For both sexes, at successive follow-up phases there was a decrease in attrition due to withdrawal and an increase due to death. Withdrawal was most prevalent between baseline and phase 2. Across the 5 years of the study total post-inclusion (post-baseline) attrition due to death accounted for a 40% (344/854) loss to cohort and total post-inclusion attrition due to withdraw a 19% (166/854) loss to cohort, with health reasons for withdrawal becoming more dominant over time. Adjusting for sex, parsimonious modelling showed only occupational class (National Statistics Socio-economic Classification) to be associated with withdrawal and only between baseline and phase 2 (routine/manual compared to managerial (OR 3.41; 95% CI [1.23 to 9.44]). CONCLUSION: Following successful recruitment, we retained a high proportion of participants from a very old age group over 5 years of longitudinal research. No strong predictors of post-inclusion attrition due to withdrawal were found, suggesting the general effectiveness of our retention strategies.

Engaging the oldest old in research: lessons from the Newcastle 85+ study.

BACKGROUND: Those aged 85 and over, the oldest old, are now the fastest growing sector of the population. Information on their health is essential to inform future planning; however, there is a paucity of up-to-date information on the oldest old, who are often excluded from research. The aim of the Newcastle 85+ Study is to investigate the health of a cohort of 85-year-olds from a biological, medical and psychosocial perspective. This paper describes the methods employed for the successful recruitment, retention and evaluation of this cohort. METHODS: Participants were all individuals born in 1921 and registered with a participating general practice in Newcastle and North Tyneside, UK. Involvement comprised detailed health assessments, by a nurse, in their usual place of residence and/or review of their general practice medical records. RESULTS: Of the 1453 individuals eligible to participate, 72% (n = 1042) were recruited; 59% (n = 851) consented to both health assessment and review of general practice records. Key factors for successful involvement included protected time to engage with family and other key gatekeepers, minimising participant burden, through for example home based assessment, and flexibility of approach. Cognitive impairment is a significant issue; due consideration should be given to the ethical and legal issues of capacity and consent. Interim withdrawal rates at phase 2 (18 month post baseline), show 88 out of 854 participants (10%) had withdrawn with approval for continued use of data and materials and a further 2 participants (0.2%) had withdrawn and requested that all data be destroyed. Attrition due to death of participants within this same time frame was 135 (16%). CONCLUSION: Our recruitment rates were good and compared favourably with other similar UK and international longitudinal studies of the oldest old. The challenges of and successful strategies for involving, recruiting and retaining the oldest old in research, including those in institutions, are described to facilitate adequate representation of this growing population in future research into ageing.