Optimal combinations of CSF biomarkers for predicting cognitive decline and clinical conversion in cognitively unimpaired participants and mild cognitive impairment patients: A multi-cohort study.

INTRODUCTION: Our objective was determining the optimal combinations of cerebrospinal fluid (CSF) biomarkers for predicting disease progression in Alzheimer's disease (AD) and other neurodegenerative diseases. METHODS: We included 1,983 participants from three different cohorts with longitudinal cognitive and clinical data, and baseline CSF levels of Aß42, Aß40, phosphorylated tau at threonine-181 (p-tau), neurofilament light (NfL), neurogranin, α-synuclein, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), glial fibrillary acidic protein (GFAP), YKL-40, S100b, and interleukin 6 (IL-6) (Elecsys NeuroToolKit). RESULTS: Change of modified Preclinical Alzheimer's Cognitive Composite (mPACC) in cognitively unimpaired (CU) was best predicted by p-tau/Aß42 alone (R2 ≥ 0.31) or together with NfL (R2  = 0.25), while p-tau/Aß42 (R2 ≥ 0.19) was sufficient to accurately predict change of the Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI) patients. P-tau/Aß42 (AUC ≥ 0.87) and p-tau/Aß42 together with NfL (AUC ≥ 0.75) were the best predictors of conversion to AD and all-cause dementia, respectively. DISCUSSION: P-tau/Aß42 is sufficient for predicting progression in AD, with very high accuracy. Adding NfL improves the prediction of all-cause dementia conversion and cognitive decline.

Quality of life and the effect of memantine in dementia with lewy bodies and Parkinson's disease dementia.

AIM: To investigate quality of life (QOL) and the effect of memantine treatment in patients with Lewy body dementias. METHODS: A secondary analysis of a randomized controlled study in 70 patients with Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB) over 24 weeks using caregiver-rated QOL-Alzheimer's disease (AD) in domains according to the WHO's classification of health. RESULTS: Baseline QOL shows lower ratings for body functions over environmental factors in DLB/PDD. Treatment with memantine significantly improves life as a whole compared to placebo and improves total QOL, body function and structure. CONCLUSION: This study shows that memantine improves QOL in Lewy body dementias. We also demonstrate important QOL patterns which can be used in clinical practice.

The effect of memantine on sleep behaviour in dementia with Lewy bodies and Parkinson's disease dementia.

OBJECTIVE: Two common and characteristic sleep disturbances have been described in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD); excessive daytime sleepiness and REM sleep behaviour disorder (RBD). This study is an analysis of a secondary outcome measure of a larger study already reported, aimed to determine whether memantine has an effect on the sleep disturbances in DLB and PDD patients. METHODS: Patients with DLB or PDD were included in a placebo-controlled, randomised controlled study of memantine (20 mg per day) for 24 weeks. The Stavanger Sleep Questionnaire and the Epworth Sleepiness Scale were used to evaluate the effect on sleep disturbances. RESULTS: Forty two patients started treatment; 20 with memantine and 22 with placebo. The primary analysis was the comparison of change between the two groups during a 24-week period, using the modified ITT population (last observation carried forward). At 24 weeks, patients treated with memantine were less physically active during sleep while patients in the placebo group worsened. Mean difference between the groups (0.5 [0.05-0.90]) was significant (p = 0.006). No significant change was observed in severity of excessive daytime sleepiness. CONCLUSIONS: Memantine decreases probable REM sleep behaviour disorder in patients with DLB and PDD. Both diagnostic groups contributed equally to the outcome.

Living with dementia with Lewy bodies: an interpretative phenomenological analysis.

OBJECTIVE: To explore the subjective experience of living with dementia with Lewy bodies (DLB). DESIGN: A qualitative study of in-depth interviews using interpretative phenomenological analysis. SETTING: A memory clinic in Malmö, southern Sweden. PARTICIPANTS: A purposive sample of five male participants with DLB between the ages of 78 and 88 years and disease duration of 1.5-7 years. RESULTS: Three themes were identified in relation to the participants' experiences of living with DLB: (1) disease impact, in terms of symptom experience and restricted participation and activities; (2) self-perception and coping strategies; (3) importance of others, such as healthcare, family and friends. CONCLUSIONS: This study provides a broad insight into the first-hand experience of living with DLB and how it compares with other dementia types. Findings highlight factors characterising the disease experience and well-being, and how persons with DLB address challenges arising secondary to disease. These findings are important for both research and clinical practice, demonstrating the feasibility of direct involvement of DLB persons in identifying important aspects of care, which include improved healthcare services.

Relative survival in patients with dementia with Lewy bodies and Parkinson's disease dementia.

INTRODUCTION: The understanding of survival in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) is limited, as well as the impact of these diagnoses in an ageing co-morbid population. METHODS: A retrospective study of 177 patients who received a DLB or PDD diagnosis between 1997-2014 at the Memory Clinic in Malmö, Sweden. Relative survival was evaluated by adjusting all-cause survival for expected survival, estimated from population life-tables, matched by sex, age and calendar year. Predictors of relative survival were investigated using multivariate regression modelling. RESULTS: At follow-up, 143 (81%) patients were deceased with a median survival of 4.1 years (IQR 2.6-6.0). After 10-years follow-up, the standardized mortality ratio was 3.44 (95% CI 2.92-4.04). Relative survival was worse with younger age at diagnosis (excess hazard ratio [eHR] 0.91, 95% CI 0.88-0.94 per year of age), female sex (eHR 1.45, 95% CI 1.01-2.09) and lower mini-mental state examination (eHR 0.93, 95% CI 0.90-0.96). Subgroup analysis (n = 141) showed higher mortality in DLB patients who were positive for APOE ɛ4 (eHR 2.00, 95% CI 1.35-2.97). CONCLUSION: The mortality is over three-times higher in patients diagnosed with dementia with Lewy bodies and Parkinson's disease dementia during a ten-year follow-up, compared to persons in the general population. Excess mortality is found primarily in younger patients, females and carriers of APOE ε4. Further research is needed regarding survival and possible interventions, including disease-modifying treatments, to improve care for this patient group.

Effects of carbonated liquid on swallowing dysfunction in dementia with Lewy bodies and Parkinson's disease dementia.

BACKGROUND: Swallowing dysfunction is an increasingly recognized problem in patients with dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), which can result in aspiration pneumonia and death. Few studies have examined potential ways of improving swallowing function in this fragile patient group. The aim of this study was to evaluate swallowing dysfunction and carbonated liquid using videofluoroscopy in DLB and PDD patients. METHODS: A total of 48 patients with DLB and PDD were referred for a clinical examination with videofluoroscopy. Descriptive overall assessments were provided at the time of the examination regarding swallowing function and the effects of different modifications, including carbonated thin liquid (CTL). Additionally, a repeated measures quantitative retrospective analysis has been performed comparing 1) thin liquids; 2) thickened liquids and 3) CTLs, with regard to the quantitative variables 1) pharyngeal transit time (PTT); 2) pharyngeal retention and 3) tracheal penetration. RESULTS: In all, 40/48 (83%) of the patients had a swallowing dysfunction, which was confirmed on videofluoroscopy, with 34/40 (85%) patients having a pharyngeal-type dysfunction. A total of 14/40 (35%) patients with an objective swallowing impairment did not have any subjective swallowing symptoms. Out of the patients with swallowing dysfunction, 87% had an overall improved swallowing function with carbonated liquid. PTT for carbonated liquid (median 633 ms, interquartile range [IQR] 516-786 ms) was quicker than for thin liquid (760 ms, IQR 613-940 ms, P=0.014) and thickened liquid (880.0 ms, IQR 600-1,500 ms, P<0.001). No significant effect was seen in residue or penetration. CONCLUSION: The majority of patients with DLB or PDD had a swallowing dysfunction, sometimes without subjective swallowing symptoms, which improved with carbonated liquid. This highlights the importance of investigating patients with videofluoroscopy and to carry out a prospective interventional study to further evaluate carbonated liquid, also addressing the effects on quality of life, aspiration and mortality.

Treatment effect of memantine on survival in dementia with Lewy bodies and Parkinson's disease with dementia: a prospective study.

OBJECTIVE: To investigate the effect on survival of treatment with memantine in patients with dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). METHODS: 75 patients with DLB and PDD were included in a prospective double-blinded randomised placebo-controlled trial (RCT) of memantine, of whom long-term follow-up was available for 42. Treatment response was recorded 24 weeks from baseline and measured by Clinical Global Impression of Change (CGIC). The participants were grouped as responders (CGIC 1-3) or non-responders (CGIC 4-7). The 24-week RCT was followed by open-label treatment and survival was recorded at 36 months. RESULTS: After 36-month follow-up, patients in the memantine group had a longer length of survival compared with patients in the placebo group (log rank x²=4.02, p=0.045). Within the active treatment group, survival analysis 36 months from baseline showed that the memantine responders, based on CGIC, had higher rates of survival compared with the non-responders (log rank x²=6.595, p=0.010). Similar results were not seen in the placebo group. CONCLUSIONS: Early treatment with memantine and a positive clinical response to memantine predicted longer survival in patients with DLB and PDD. This suggests a possible disease-modifying effect and also has implications for health economic analysis. However, owing to the small study sample, our results should merely be considered as generating a hypothesis which needs to be evaluated in larger studies. TRIAL REGISTRATION NUMBER: ISRCTN89624516.