Mortality Risks and Causes of Death by Dementia Types in a Japanese Cohort with Dementia: NCGG-STORIES.

BACKGROUND: Prognosis-related information regarding dementia needs to be updated, as changes in medical and long-term care environments for patients with dementia in recent decades may be improving the prognosis of the disease. OBJECTIVE: We aimed to investigate the mortality, cause of death, and prognostic factors by types of dementia in a Japanese clinic-based cohort. METHODS: The National Center for Geriatrics and Gerontology-Life Stories of People with Dementia consists of clinical records and prognostic data of patients who visited the Memory Clinic in Japan. Patients who attended the clinic between July 2010 and September 2018, or their close relatives, were asked about death information via a postal survey. A cohort of 3,229 patients (mean age, 76.9; female, 1,953) was classified into six groups: normal cognition (NC), mild cognitive impairment (MCI), Alzheimer's disease (AD), vascular dementia, dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration. A Cox proportional hazards model was employed to compare the mortality of each type of dementia, MCI, and NC. RESULTS: Patients with all types of dementia and MCI had higher mortality rates than those with NC (hazard risks: 2.61-5.20). The most common cause of death was pneumonia, followed by cancer. In the MCI, AD, and DLB groups, older age, male sex, and low cognitive function were common prognostic factors but not presence of apolipoprotein E ɛ4 allele. CONCLUSION: Our findings suggest important differences in the mortality risk and cause of death among patients with dementia, which will be useful in advanced care planning and policymaking.

Seizure occurrence and related mortality in dementia with Lewy bodies.

Dementia is a risk factor for epilepsy. While seizures have a well-established association with Alzheimer's disease (AD), their association with dementia with Lewy bodies (DLB) is not established. We utilized the National Alzheimer's Coordinating Centers' Uniform Data Set (NACC-UDS V1-3) to analyze occurrence of seizures in DLB and seizure occurrence associations with mortality. We excluded subjects with conventional seizure risk factors. Seizure occurrence was noted in 36 subjects (2.62%) out of 1376 subjects with DLB. Among 500 subjects with pathologically confirmed DLB, seizure occurrence was documented in 19 (3.8%) subjects. Half of the subjects had onset of seizures three years before or after DLB diagnosis. Two-year mortality for subjects with DLB with seizures was high at 52.8% but no increased risk was noted as compared with subjects with DLB without seizures. More prospective and long-term longitudinal studies are needed to clarify relationships between DLB, seizure occurrence, and risk of increased mortality.

Survival among the older adults with clinical signs of Lewy body dementia in 40 Swedish nursing homes: a 6-year follow-up study.

OBJECTIVES: To investigate survival among elderly residents of Swedish nursing homes (NHs), with specific focus on those with two or more signs of Lewy body dementia (LBD). DESIGN: Prospective observational study. SETTING: NHs in Malmö, the third largest city in Sweden. PARTICIPANTS: The study population was older adults (aged ≥65 years) living in the 40 NHs in Malmö. Clinical data were collected with a customised questionnaire assessing core clinical LBD signs. Patients were categorised based on 0-1 or 2-4 LBD signs. The head nurse at each NH collected the study data: LBD questionnaires, electronic medication lists and electronic medical records from 2012 to 2013. MAIN OUTCOME MEASURES: 80-month mortality. RESULTS: Five hundred and fifty-eight (96%) of the residents were deceased at follow-up; among these, mean (95% CI) overall survival time was 29 (28-31) months. Mean survival differed between the LBD groups; those with 0-1 LBD signs lived 8 months longer than those with 2-4 LBD signs. Mortality risk for residents in the LBD 2-4 group was also significantly higher. HR adjusted for age and sex was HR (95% CI) 1.60 (1.30 to 1.97). Mortality risk was also significantly higher in residents with signs of fluctuating cognition 1.36 (1.15 to 1.62), rapid eye movement sleep behaviour disorder 1.49 (1.11 to 1.98), balance problems 1.36 (1.14 to 1.61) or rigidity 1.41 (1.18 to 1.68). CONCLUSIONS: This large, longitudinal study shows the important survival effects of identifying and diagnosing older adults NH residents who have two or more LBD signs.

Clinical Presentation, Diagnostic Features, and Mortality in Dementia with Lewy Bodies.

BACKGROUND: Dementia with Lewy bodies (DLB) is the second most common degenerative dementia in older people. However, rates of misdiagnosis are high, and little is known of its natural history and outcomes. Very few previous studies have been able to access routine clinical information for large, unbiased DLB cohorts in order to establish initial presentation, neuropsychological profile, and mortality. OBJECTIVE: To examine in detail, symptom patterns at presentation and their association with outcomes, including mortality, in a large naturalistic DLB cohort from a secondary care sample. METHODS: A retrospective cohort design was used to identify a DLB cohort (n = 251) from Cambridgeshire and Peterborough NHS Foundation Trust (CPFT). Information relating to first consultation, diagnosis, and DLB diagnostic features were extracted. RESULTS: A wide range of presenting complaints and differential initial diagnoses were identified for the cohort. Along with memory loss (27.1%) and hallucinations (25.4%), low mood (25.1%) was noted as a key presenting complaint among the DLB cohort. Rates of REM sleep disorder were considerably lower (8.4%) than would be expected. Deficits in non-amnestic cognitive domains were associated with reduced mortality compared with amnestic-only presentations. CONCLUSION: Individuals later diagnosed with DLB present initially to secondary care with a wide range of symptoms and complaints, some of which are not immediately suggestive of a DLB diagnosis. More examinations of large cohorts such as this are needed to further elucidate the complex presentation and clinical course of DLB, and to confirm whether amnestic-only presentation confers a worse outcome.

Survival time and differences between dementia with Lewy bodies and Alzheimer's disease following diagnosis: A meta-analysis of longitudinal studies.

OBJECTIVE: To synthesize the evidence across longitudinal studies comparing survival in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). METHODS: We conducted a systematic review and meta-analysis of studies comparing survival in clinically diagnosed DLB to AD. Longitudinal cohort studies were identified through a systematic search of major electronic databases from inception to May 2018. A random effects meta-analysis was performed to calculate survival time and relative risk of death. RESULTS: Overall, 11 studies were identified including 22,952 patients with dementia: 2029 with DLB (mean diagnosis age 76.3; 47% female) compared with 20,923 with AD (mean diagnosis age 77.2; 65.1% female). Average survival time in DLB from diagnosis was 4.11 years (SD ± 4.10) and in AD 5.66 (SD ± 5.32) years, equating to a 1.60 (95% CI: -2.44 to -0.77) years shorter survival in DLB (p < 0.01). Relative risk of death was increased by 1.35 (95%CI: 1.17-1.55) in DLB compared to AD (p < 0.01). Differences in survival were not explained by follow-up time, age at diagnosis, gender, or cognitive score. CONCLUSIONS: There is consistent evidence for higher and earlier mortality in DLB compared to AD. This is important for all stakeholders and underlines the importance of expanding research into DLB.

Cause of Death and End-of-Life Experiences in Individuals with Dementia with Lewy Bodies.

OBJECTIVES: To investigate the natural history, cause of death, and end-of-life experiences of individuals diagnosed with dementia with Lewy bodies (DLB). DESIGN: Twenty-question online survey administered through the Lewy Body Dementia Association. SETTING: United States. PARTICIPANTS: Caregivers, family, and friends of individuals who died in the past 5 years with a diagnosis of DLB (survey respondents: n = 658, 89% female, median age 50-69). MEASUREMENTS: The survey included 3 questions about the respondent's background and 17 about the end-of-life experiences of the person with DLB. Topics included time from symptom onset and diagnosis to death, cause of death, advance directive completion, end-of-life education, hospice use, and location of death. Results were analyzed descriptively. RESULTS: Most individuals with DLB died within 5 years of diagnosis (median 3-4 years). Respondents indicated that physicians rarely discussed what to expect at the end of life (40% total, but only 22% to a helpful degree) and that the caregiver usually initiated such conversations. Death was usually expected, but fewer than half of respondents felt prepared for what to expect. Seventy-eight percent used hospice, usually at home or in skilled care, with wide variations in duration. Failure to thrive was the most common cause of death (65%), followed by pneumonia and swallowing difficulties (23%), other medical conditions (19%), and complications from falling (10%) (multiple causes allowed). CONCLUSION: Study results highlight a critical need for better prognostic counseling and education for persons and families living with DLB. The results of the current study can inform such counseling, but additional studies are needed to further explore expected prognosis of individuals diagnosed clinically with DLB and optimal use of palliative care services. J Am Geriatr Soc 67:67-73, 2019.

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.

No Significant Difference in Cognitive Decline and Mortality between Parkinson's Disease Dementia and Dementia with Lewy Bodies: Naturalistic Longitudinal Data from the Swedish Dementia Registry.

BACKGROUND: Whether dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are distinct disorders or two subtypes of the same entity, is not yet fully understood. There is a dearth of knowledge on differences in longitudinal clinical outcomes between DLB and PDD. OBJECTIVE: We aimed to compare longitudinal trend of cognitive decline, mortality, and their determinant factors between patients with DLB and PDD. METHODS: At baseline, we recruited 1110 DLB, and 764 PDD patients registered in the Swedish dementia registry (SveDem) during 2007-2015. Cognitive status was assessed at baseline and each follow-up visit by mini-mental state examination (MMSE). At least one follow-up MMSE was available for 411 (37.0%) DLB and 229 (30.0%) PDD patients. Rate of cognitive decline and mortality risk were compared between the two groups. RESULTS: After an average of 2-years, the rate of cognitive decline did not differ between DLB (1.1 MMSE unit/year) and PDD (1.2 MMSE unit/year) groups (p = 0.970). There was no significant difference in the median survival time between DLB (4.0 years) and PDD (4.1 years) groups (Log rank p = 0.614). Antipsychotic drug use in DLB and larger number of medications in PDD were the most important determinants of faster annual cognitive decline. CONCLUSIONS: Our findings from real-world clinical practice demonstrated that the rate of cognitive decline and mortality do not differ significantly between DLB and PDD at least over 2 years, yet, various factors might determine clinical outcome in these two groups. It seems that DLB and PDD are probably similar synucleinopathies, with phenotypical variations in the order of manifestations rather than course of progression and clinical outcome.

Mortality in dementia with Lewy bodies compared with Alzheimer's dementia: a retrospective naturalistic cohort study.

OBJECTIVES: To use routine clinical data to investigate survival in dementia with Lewy bodies (DLB) compared with Alzheimer's dementia (AD). DLB is the second most common dementia subtype after AD, accounting for around 7% of dementia diagnoses in secondary care, though studies suggest that it is underdiagnosed by up to 50%. Most previous studies of DLB have been based on select research cohorts, so little is known about the outcome of the disease in routine healthcare settings. SETTING: Cambridgeshire & Peterborough NHS Foundation Trust, a mental health trust providing secondary mental health care in England. SAMPLE: 251 DLB and 222 AD identified from an anonymised database derived from electronic clinical case records across an 8-year period (2005-2012), with mortality data updated to May 2015. RESULTS: Raw (uncorrected) median survival was 3.72 years for DLB (95% CI 3.33 to 4.14) and 6.95 years for AD (95% CI 5.78 to 8.12). Controlling for age at diagnosis, comorbidity and antipsychotic prescribing the model predicted median survival for DLB was 3.3 years (95% CI 2.88 to 3.83) for males and 4.0 years (95% CI 3.55 to 5.00) for females, while median survival for AD was 6.7 years (95% CI 5.27 to 8.51) for males and 7.0 years (95% CI 5.92 to 8.73) for females. CONCLUSION: Survival from first presentation with cognitive impairment was markedly shorter in DLB compared with AD, independent of age, sex, physical comorbidity or antipsychotic prescribing. This finding, in one of the largest clinical cohorts of DLB cases assembled to date, adds to existing evidence for poorer survival for DLB versus AD. There is an urgent need for further research to understand possible mechanisms accounting for this finding.

Survival and Causes of Death Among People With Clinically Diagnosed Synucleinopathies With Parkinsonism: A Population-Based Study.

Importance: To our knowledge, a comprehensive study of the survival and causes of death of persons with synucleinopathies compared with the general population has not been conducted. Understanding the long-term outcomes of these conditions may inform patients and caregivers of the expected disease duration and may help with care planning. Objective: To compare survival rates and causes of death among patients with incident, clinically diagnosed synucleinopathies and age- and sex-matched referent participants. Design, Setting, and Participants: This population-based study used the Rochester Epidemiology Project medical records-linkage system to identify all residents in Olmsted County, Minnesota, who received a diagnostic code of parkinsonism from 1991 through 2010. A movement-disorders specialist reviewed the medical records of each individual to confirm the presence of parkinsonism and determine the type of synucleinopathy. For each confirmed patient, an age- and sex-matched Olmsted County resident without parkinsonism was also identified. Main Outcomes and Measures: We determined the age- and sex-adjusted risk of death for each type of synucleinopathy, the median time from diagnosis to death, and the causes of death. Results: Of the 461 patients with synucleinopathies, 279 (60.5%) were men, and of the 452 referent participants, 272 (60.2%) were men. From 1991 through 2010, 461 individuals received a diagnosis of a synucleinopathy (309 [67%] of Parkinson disease, 81 [17.6%] of dementia with Lewy bodies, 55 [11.9%] of Parkinson disease dementia, and 16 [3.5%] of multiple system atrophy with parkinsonism). During follow-up, 68.6% (n = 316) of the patients with synucleinopathies and 48.7% (n = 220) of the referent participants died. Patients with any synucleinopathy died a median of 2 years earlier than referent participants. Patients with multiple system atrophy with parkinsonism (hazard ratio, 10.51; 95% CI, 2.92-37.82) had the highest risk of death compared with referent participants, followed by those with dementia with Lewy bodies (hazard ratio, 3.94; 95% CI, 2.61-5.94), Parkinson disease with dementia (hazard ratio, 3.86; 95% CI, 2.36-6.30), and Parkinson disease (hazard ratio, 1.75; 95% CI, 1.39-2.21). Neurodegenerative disease was the most frequent cause of death listed on the death certificate for patients, and cardiovascular disease was the most frequent cause of death among referent participants. Conclusions and Relevance: Individuals with multiple system atrophy with parkinsonism, dementia with Lewy bodies, and Parkinson disease dementia have increased mortality compared with the general population. The mortality among persons with Parkinson disease is only moderately increased compared with the general population.

Concomitant AD pathology affects clinical manifestation and survival in dementia with Lewy bodies.

OBJECTIVE: To investigate whether concomitant Alzheimer's disease (AD) pathology, reflected by cerebrospinal fluid (CSF) biomarkers, has an impact on dementia with Lewy bodies (DLB) in terms of clinical presentation, cognitive decline, nursing home admittance and survival. PARTICIPANTS: We selected 111 patients with probable DLB and CSF available from the Amsterdam Dementia Cohort. On the basis of the AD biomarker profile (CSF tau/amyloid-ß 1-42 (Aß42) ratio >0.52), we divided patients into a DLB/AD+ and DLB/AD- group. Of the 111 patients, 42 (38%) had an AD CSF biomarker profile. We investigated differences between groups in memory, attention, executive functions, language and visuospatial functions. Difference in global cognitive decline (repeated Mini-Mental State Examination (MMSE)) was investigated using linear mixed models. Cox proportional hazard analyses were used to investigate the effects of the AD biomarker profile on time to nursing home admittance and time to death. RESULTS: Memory performance was worse in DLB/AD+ patients compared with DLB/AD- patients (p<0.01), also after correction for age and sex. Hallucinations were more frequent in DLB/AD+ (OR=3.34, 95% CI 1.22-9.18). There was no significant difference in the rate of cognitive decline. DLB/AD+ patients had a higher mortality risk (HR=3.13, 95% CI 1.57 to 6.24) and nursing home admittance risk (HR=11.70, 95% CI 3.74 to 36.55) compared with DLB/AD- patients. CONCLUSIONS: DLB-patients with a CSF AD profile have a more severe manifestation of the disease and a higher risk of institutionalisation and mortality. In clinical practice, CSF biomarkers may aid in predicting prognosis in DLB. In addition, DLB-patients with positive AD biomarkers could benefit from future treatment targeting AD pathology.

Causes of Death According to Death Certificates in Individuals with Dementia: A Cohort from the Swedish Dementia Registry.

OBJECTIVES: The causes of death in dementia are not established, particularly in rarer dementias. The aim of this study is to calculate risk of death from specific causes for a broader spectrum of dementia diagnoses. DESIGN: Cohort study. SETTING: Swedish Dementia Registry (SveDem), 2007-2012. PARTICIPANTS: Individuals with incident dementia registered in SveDem (N = 28,609); median follow-up 741 days. Observed deaths were 5,368 (19%). MEASUREMENTS: Information on number of deaths and causes of mortality was obtained from death certificates. Odds ratios for the presence of dementia on death certificates were calculated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox hazards regression for cause-specific mortality, using Alzheimer's dementia (AD) as reference. Hazard ratios for death for each specific cause of death were compared with hazard ratios of death from all causes (P-values from t-tests). RESULTS: The most frequent underlying cause of death in this cohort was cardiovascular (37%), followed by dementia (30%). Dementia and cardiovascular causes appeared as main or contributory causes on 63% of certificates, followed by respiratory (26%). Dementia was mentioned less in vascular dementia (VaD; 57%). Compared to AD, cardiovascular mortality was higher in individuals with VaD than in those with AD (HR = 1.82, 95% CI = 1.64-2.02). Respiratory death was higher in individuals with Lewy body dementia (LBD, including Parkinson's disease dementia and dementia with Lewy bodies, HR = 2.16, 95% CI = 1.71-2.71), and the risk of respiratory death was higher than expected from the risk for all-cause mortality. Participants with frontotemporal dementia were more likely to die from external causes of death than those with AD (HR = 2.86, 95% CI = 1.53-5.32). CONCLUSION: Dementia is underreported on death certificates as main and contributory causes. Individuals with LBD had a higher risk of respiratory death than those with AD.

Reporting of clinically diagnosed dementia on death certificates: retrospective cohort study.

BACKGROUND: mortality statistics are a frequently used source of information on deaths in dementia but are limited by concerns over accuracy. OBJECTIVE: to investigate the frequency with which clinically diagnosed dementia is recorded on death certificates, including predictive factors. METHODS: a retrospective cohort study assembled using a large mental healthcare database in South London, linked to Office for National Statistics mortality data. People with a clinical diagnosis of dementia, aged 65 or older, who died between 2006 and 2013 were included. The main outcome was death certificate recording of dementia. RESULTS: in total, 7,115 people were identified. Dementia was recorded on 3,815 (53.6%) death certificates. Frequency of dementia recording increased from 39.9% (2006) to 63.0% (2013) (odds ratio (OR) per year increment 1.11, 95% CI 1.07-1.15). Recording of dementia was more likely if people were older (OR per year increment 1.02, 95% CI 1.01-1.03), and for those who died in care homes (OR 1.89, 95% CI 1.50-2.40) or hospitals (OR 1.14, 95% CI 1.03-1.46) compared with home, and less likely for people with less severe cognitive impairment (OR 0.95, 95% CI 0.94-0.96), and if the diagnosis was Lewy body (OR 0.30, 95% CI 0.15-0.62) or vascular dementia (OR 0.79, 95% CI 0.68-0.93) compared with Alzheimer's disease. CONCLUSIONS: changes in certification practices may have contributed to the rise in recorded prevalence of dementia from mortality data. However, mortality data still considerably underestimate the population burden of dementia. Potential biases affecting recording of dementia need to be taken into account when interpreting mortality data.

Predicting Survival in Dementia With Lewy Bodies With Hippocampal Volumetry.

BACKGROUND: The clinical course of dementia with Lewy bodies patients is heterogeneous. The ability to more accurately prognosticate survival is important. OBJECTIVE: The objective of this study was to investigate hippocampal volume as a predictor of survival in dementia with Lewy bodies patients. METHODS: Survival analysis for time from onset of cognitive symptoms to death was carried out using Cox proportional hazards models. Given their age and total intracranial volume, patients were dichotomized into low/medium (0%-66.7%) and high (66. 7%-100%) hippocampal volume categories. The models using these categories to predict survival were adjusted for field strength, APOE ε4 status, and estimated onset age of cognitive problems. RESULTS: We investigated 167 consecutive patients with dementia with Lewy bodies. The median age at MRI was 72 years (interquartile range 67-76), and 80% were male. The median time from estimated first cognitive symptom to death was 7.4 years (interquartile range:5.7-10.2). Lower hippocampal volumes were significantly associated with higher risk of death (hazard ratio 1.28; 95% confidence interval 1.04-1.58; P = .024). The predicted median survival for participants with onset of cognitive symptoms at age 68 was 10.63 years (95% confidence interval 8.66-14.54) for APOE ε4 negative, high hippocampal volume participants; 8.89 years (95% confidence interval 7.56-12.36) for APOE ε4 positive, high hippocampal volume participants; 8.10 years (95% confidence interval 7.34-11.08) for APOE ε4 negative, low/medium hippocampal volume participants; and 7.38 (95% confidence interval 6.74-9.29) years for APOE ε4 positive, low/medium hippocampal volume participants. CONCLUSIONS: Among patients with clinically diagnosed dementia with Lewy bodies, those with neuroimaging evidence of hippocampal atrophy have shorter survival times. © 2016 International Parkinson and Movement Disorder Society.

Akinetic crisis in dementia with Lewy bodies.

BACKGROUND AND PURPOSE: Dementia with Lewy bodies (DLB) is characterised by neuroleptic hypersensitivity. It is unclear, however, whether the neuroleptic hypersensitivity implies an increased incidence of neuroleptic malignant syndrome (NMS) or of akinetic crisis (AC), which are expressions of the same possibly lethal clinical event, and whether AC in DLB can appear independently of neuroleptic treatment. In our prospective study, we assessed the incidence of AC in a cohort of DLB as compared with that in patients with Parkinson disease (PD). METHODS: In total, 614 patients with PD and 236 DLB were recruited and followed during 2005-2013. AC was diagnosed as sudden akinetic state unresponsive to dopaminergic rescue drugs, dysphagia and serological alterations without recovery for 48 h or more requiring hospital admission. Exposure to neuroleptics was specifically evaluated, because of the high implicit risk in DLB. RESULTS: 24 patients with PD (3.9%) and 16 patients with DLB (6.8%) developed AC. 77 (32.6%) DLB and 32 (5.2%) PD were exposed to typical neuroleptics, but only 8 DLB and 3 PD presented with AC. Disease duration before AC was lower in DLB than in PD group (p<0.01). Outcome was fatal in 8 patients with (50%) DLB and 3 (12.5%) PD (p=0.05). When age and use of neuroleptics were adjusted for into a Cox proportional hazards model predicting time to AC, the HR of patients with DLB was 13.0 (95% CI 4.23 to 39.9; p<0.001). CONCLUSIONS: AC in DLB can appear independently of neuroleptic treatment, occurs earlier and is more frequently fatal than in PD.

Influence of pneumonia complications on the prognosis of patients with autopsy-confirmed Alzheimer's disease, dementia with Lewy bodies, and vascular dementia.

BACKGROUND: Pneumonia is a major, complicated disease in patients with dementia. However, the influence of pneumonia on the prognosis of patients with varying types of dementia has not been fully evaluated. METHODS: We retrospectively analyzed the data from medical and autopsy reports. All study patients had been hospitalized and underwent brain autopsy in a hospital in Toyohashi, Japan, between 2005 and 2014. The patients with subtypes of dementia, specifically Alzheimer's disease (AD), dementia with Lewy bodies (DLB), or vascular dementia (VaD), were neuropathologically diagnosed and examined. Pneumonia incidence, cause of death, and the clinical time-course of dementia were compared among the dementia subtypes. The time to death from dementia onset (survival time) was compared by the Kaplan-Meier method among subtypes of dementia with or without pneumonia. Risk factors for survival time on all study patients were analyzed with the Cox proportional hazard model. RESULTS: Of the 157 eligible patients, 63 (40.1%) had AD, 42 (26.8%) had DLB, and 52 (33.1%) had VaD. Pneumonia complication was observed with high incidence in each subtype of dementia, especially in DLB (90.5%). The median total duration from dementia onset to death was 8 years in AD and DLB, and 5 years in VaD. The VaD subtype had more male patients than AD or DLB (P = 0.010), and age of death in this group was the youngest among the three groups (P = 0.018). A significant difference was observed in the survival time by the Kaplan-Meier method among the three groups (P < 0.001) and among the groups with pneumonia (P = 0.002). The factors associated with shorter survival time were male gender, pneumonia complications, diabetes mellitus, age of dementia onset ≥ 75 years, and VaD. CONCLUSIONS: Pneumonia complications shortened the survival time of patients with AD, DLB, and VaD.

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.

Long-term mortality in a cohort of home-dwelling elderly with mild Alzheimer's disease and Lewy body dementia.

OBJECTIVE: To study mortality in subjects with mild dementia in Norway with a special focus on patients with Lewy body dementia (LBD) compared to Alzheimer's disease (AD). METHODS: All referrals of mild dementia patients to dementia clinics in western Norway from March 2005 to March 2007 were included and followed until December 2012. Diagnoses were based on a comprehensive standardized assessment program. RESULTS: Of 209 patients, 137 (66%) had AD and 53 (25%) had LBD. Dementia was associated with increased mortality (standardized mortality ratio = 1.8, AD 1.5, LBD 2.6). The median survival time was 6.2 years (95% CI 5.4-6.9). Predictors of mortality were age at diagnosis (HR 1.1 per year) and LBD diagnosis (HR 2.4). CONCLUSION: Dementia patients had an increased mortality, particularly those with LBD.

[Alzheimer's disease and related disorders: specificity of young onset patients, including ethical aspects]. / Maladie d'Alzheimer et syndromes apparentés : spécificités des « malades jeunes ¼, réflexions cliniques et éthiques.

The number of patients with young onset dementia (YOD) (that is before age 65) is estimated at 32,000 in France, and 5000 with onset dementia before 60 years. These patients differ from older ones by the greater number of rares causes (29%), heterogeneity of the presentation among the usual diseases, such as non-amnestic phenotypes of Alzheimer's disease, high frequency of frontal symptoms, and possible genetic origin. These aspects must be taken into account for the diagnosis, often more difficult than in older ones because patients have a little knowledge of the YOD, excepted in the genetics forms. YOD patients can still work or drive a car, and we should choose between the respect for autonomy and the security for the patient and their carers. YOD patients can be more often included in pharmacological trials because they have lower associated disorders. Individual non-pharmacological treatment should be priviledged because they don't easily accept collective activities with other patients over 60 years of age. Excepted for the very young patients (onset before 45), the survival is longer than in late onset dementia, with sometimes severe behavioral problems related to frontal syndrome. In France, the caregiving at home has been improved since the possibility for the YOD patients to receive a financial assistance reserved for the disabled patients, but admission to a nursing home before 60 is very difficult and increases the caregiver burden and perception of unfairness. There is a discrimination between young or older demented patients related to the great difficulty to meet the needs of younger patients, due to the rigidity of the medical and social systems. The presentation of a limited offer for the YOD patients must initiate reflections on our capacities to respect the autonomy and the dignity of the Alzheimer's patients regardless of age.

Differences in survival between patients with dementia with Lewy bodies and patients with Alzheimer's disease--measured from a fixed cognitive level.

INTRODUCTION: The aim of this study was to compare survival in patients with Alzheimer's disease (AD) and patients with dementia with Lewy bodies (DLB). Since anamnestic and retrospective information about disease duration are unreliable variables, we measured survival from a fixed cognitive level. METHODS: Survival time was measured from the reported disease onset, from the time of diagnosis, from Mini-Mental State Examination (MMSE) 20 ± 1, and from MMSE 17 ± 1. RESULTS: Survival time was significantly shorter in the DLB group compared to the AD group both from the time of diagnosis and from the cognitive levels of 20 and 17 on the MMSE. There was no difference in survival when measured from the reported disease onset. DISCUSSION: Our findings indicate that DLB patients have a more malignant clinical course. Our method of investigating survival in a cognitively homogenous population may gain scientific power. Reliable methods to predict survival and the clinical course are of great value for patients, caregivers, doctors, and society.