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.

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.

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.

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.

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.

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.

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.

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.

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.

The influence of vascular risk factors on the survival rate of patients with dementia with Lewy bodies and Alzheimer disease.

BACKGROUND AND PURPOSE: The aim of this study was to determine whether dementia with Lewy bodies (DLB) progres-ses more rapidly than Alzheimer disease (AD) and to compare survival after dementia onset and mortality in both dementia groups. MATERIAL AND METHODS: A medical records analysis of AD (n = 183) and DLB (n = 51) patients was performed to determine age at onset of symptoms, the date of first presentation to the psychiatric services, dementia severity at diagnosis (MMSE score), and mean disease duration before diagnosis. Categorical data regarding vascular risk factors were collected. Projected decline rate (MMSE/year), survival rate after the diagnosis of dementia, mean survival time after diagnosis and mortality rate were calculated and compared between DLB and AD groups. RESULTS: The comparison of clinical and demographic parameters revealed no significant differences between groups, apart from a more pronounced decline rate in the DLB group. Diabetes, and to a lesser extent hypertension, influenced survival in AD, but not in DLB subjects. Overall, however, the difference in mortality rates and survival time between DLB and AD subjects cannot be attributed to the presence of any vascular risk factor analysed. DLB, independently of the presence of vascular risk factors, seems to be a more aggressive disorder than AD, when mortality and survival time are taken into account. CONCLUSIONS: More rapid progression of cognitive decline and shorter duration of dementia were found in DLB in this naturalistic study. The findings may have important implications for the management and treatment of DLB and should be confirmed in prospective studies.

Incidence and survival of dementia in a general population of Japanese elderly: the Hisayama study.

OBJECTIVE: To estimate the incidence and survival rates of total and cause specific dementia in a general Japanese population. METHODS: A total of 828 subjects without dementia, aged 65 years or over, were followed-up prospectively for 17 years. Dementia was subdivided into cause specific subtypes: namely, Alzheimer's disease (AD), vascular dementia (VD), dementia with Lewy bodies (DLB), combined dementia and other types of dementia. During the follow-up, 275 subjects developed dementia; of these, 251 (91.2%) were evaluated morphologically, with 164 subjected to brain autopsy examination and the remaining 87 to neuroimaging. RESULTS: The incidences of total dementia, AD, VD, DLB, combined dementia and other types of dementia were 32.3 (n = 275), 14.6 (124), 9.5 (81), 1.4 (12), 3.8 (33), and 3.1 (16) per 1000 person years, respectively. The incidences of AD, combined dementia and other types of dementia rose with increasing age, particularly after the age of 85 years, but this tendency was not observed for VD or DLB. The survival curve of dementia cases aged 65-89 years was significantly lower than that of age and sex matched controls (10 year survival rate, 13.6% vs 29.3%; hazard ratio 1.67; 95% confidence interval 1.31 to 2.13). The 10 year survival rates were not significantly different among dementia subtypes. CONCLUSIONS: Our findings suggest that the Japanese elderly population has a high risk for the development of dementia, specifically AD and VD, and once dementia is established, the risk of death is considerable.

Differences in clinical course between dementia with Lewy bodies and Alzheimer's disease.

BACKGROUND AND PURPOSE: To investigate whether there may be differences in the clinical course and changes in cognitive progression between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). METHODS: We compared the time from the first visit to endpoints (discontinuation of visits because of admission, death, or institutionalization) between 56 patients with DLB and 111 patients with AD. Mini-Mental State Examination (MMSE) scores of patients were every 12 months examined up to 60 months. RESULTS: Dementia with Lewy bodies had a significantly shorter time to reaching endpoints than those with AD (median time; 40 months vs. 52 months, P < 0.0001). The proportion of admission (or death) was significantly higher in DLB than in AD (30% vs. 14%, P < 0.05), while the difference in institutionalization in nursing homes did not reach statistical significance (25% vs. 17%). Rates of longitudinal MMSE score decline for DLB and AD groups were equivalent. CONCLUSION: Dementia with Lewy bodies had a greater risk of admission (or death) because of most commonly fall-related injuries and bronchopneumonia than AD, but the two groups did not differ in rate of cognitive decline.

Cerebrospinal fluid total tau is associated with shorter survival in dementia with Lewy bodies.

A pathology typical of dementia with Lewy bodies (DLB) has been demonstrated to increase mortality to a greater extent than the pathology of Alzheimer's disease (AD). However, mortality in DLB has also been shown to increase with concomitant AD pathology. Furthermore, in a recent publication, we showed that there is a robust and specific increase in CSF calcium and magnesium in DLB patients compared to both AD patients and controls. Thus, in order to explore the influence of CSF AD markers and trace element concentrations on mortality in DLB, we undertook a longitudinal prospective study of 47 clinically diagnosed DLB patients and 157 AD patients as well as 49 healthy volunteers. Both AD and DLB patients showed an increased mortality compared to the healthy controls (relative risk: 10 and 8, respectively; p < 0.001). Increased levels of CSF total tau were associated with increased mortality among the DLB patients (p < 0.05), but not among the AD patients or controls. Gender, age, MMSE score, Abeta42 concentration and phosphorylated tau, and CSF trace element concentrations did not influence survival in the obtained models.

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.

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.

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.

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.

Age and apoE associations with complex pathologic features in Alzheimer's disease.

The risk for Alzheimer's disease (AD) is influenced by both age and ApoE status. The present study addresses the associations of age and ApoE status on complex pathologic features in AD (n=81) including coexistent cerebrovascular disease (CVD), argyrophilic grain disease (AGD), and Lewy body disease (LBD). The frequency of coexistent cerebrovascular disease increased with increasing age. Age and ApoE status were differentially associated with atherosclerosis, lacunar infarctions, and microvascular pathology. Coexistent Lewy body pathology was negatively associated with age, dropping off abruptly after age 90. The presence of an ApoE epsilon4 allele was associated with an increased frequency of coexistent LBD. Logistic regression analyses demonstrated both dependent and independent effects of age and ApoE status on the presence of coexistent Lewy body pathology in AD. While the decreasing frequency of LBD in AD after age 90 could be partly accounted for by a lower probability of an ApoE epsilon4 allele, the independent association with age suggests either 1) a survival effect, 2) decreased incidence with advancing age, or 3) both.

Early-onset dementia is associated with higher mortality.

BACKGROUND/AIMS: Our objective was to compare the mortality risks of patients with early- and late-onset dementia with non-demented controls of the same age range and to analyse the mortality risks in subtypes of dementia. METHODS: We included 1,203 subjects from our memory clinic. Patients with dementia were subdivided into 2 groups, with early- (<65 years) or late-onset dementia (>or=65 years), and compared with non-demented controls of the same age range. We used Cox proportional hazard models to estimate mortality risks. RESULTS: When compared to non-demented controls of the same age range, the patients with early-onset dementia had a strongly elevated mortality risk [hazard ratio (95% confidence interval) = 43.3 (3.1-600.4)], while those with late-onset dementia had a moderately increased mortality risk compared to older controls [hazard ratio (95% confidence interval) = 3.4 (1.8-6.2)]. An additional analysis showed that, adjusted for age, Alzheimer's disease seemed to have the most benign course, with a fourfold increased mortality risk. Dementia with Lewy bodies and vascular dementia (frequently seen at older age) and frontotemporal lobar degeneration and 'other dementias' (often found at younger age) had a six- to eightfold increased mortality risk. CONCLUSION: Dementia is a risk factor for death. Especially in young patients the impact of dementia on mortality is high.

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.