Unspecified Dementia Research Articles

The Real-World Medicare Costs of Alzheimer Disease: Considerations for Policy and Care.

Headlines in popular media suggest that Alzheimer disease will bankrupt the Medicare program. Indeed, Alzheimer disease affects more than 5 million older Medicare beneficiaries. To compare total Medicare-covered (allowed) costs of patients with Alzheimer disease with the risk adjusted costs of beneficiaries without dementia over their last years of life, using claims data. Using the Medicare 5 Percent Limited Data Set claim files from 2006-2015, we conducted a cost impact analysis of costs for up to 8 years before the year of death. Risk adjustment was performed at a beneficiary level using Medicare's 2015 Hierarchical Condition Categories. Beneficiaries were classified into dementia categories based on their diagnoses during the last 3 years of life. Costs were trend adjusted to 2015. This study found that 40% of deceased beneficiaries have Alzheimer disease or unspecified dementia diagnoses in their claims history. In their last 9 years of life, Alzheimer disease added about 11% to the average $17,000 per year Medicare cost for same-risk beneficiaries without dementia. Like many diseases, Alzheimer disease and dementia are associated with aging, but unlike other diseases, families and Medicaid, rather than Medicare, bear most of the substantial cost burden. As research continues into Alzheimer treatments, it is not too early to consider how to better integrate Medicare and Medicaid to fund and improve patient outcomes, which will likely involve better diagnosis, treatment, and care coordination. Funding for this project was provided by the Alliance for Aging Research, which received funding from Biogen, Eli Lilly, and Janssen Pharmaceuticals. Peschin and Jenkins are employed by the Alliance for Aging Research. Scott was employed by the Alliance for Aging Research at the time of this study and also reports consulting fees from Piramal Imaging, General Electric, and Allergan, outside of this study. Scott is chair of the Board of Directors for the Alliance for Aging Research, which is a volunteer position, and is also president of Applied Policy, a health policy and reimbursement consultancy. Pyenson and Steffens are employed by Milliman, which was contracted to work on this study. Goss Sawhney and Rotter were employed by Milliman at the time this work was performed. Milliman is a consultant to thousands of organizations in the health care industry.

The main neurologic diagnoses from a neurology outpatient clinic in Rio de Janeiro, Brazil.

This study aims to evaluate the prevalence, distribution and clinical profile of neurological diseases and syndromes from a neurology outpatient clinic in the city of Rio de Janeiro. This is a quantitative, cross-sectional study. 180 medical records of firsttime visits conducted through 18 months were analyzed. Age, gender and comorbidities were collected to identify the sample’s profile and the neurological diagnoses found were classified in predefined groups of syndromes according to the ICD-10 classification, which were further stratified according to age and gender. 157 (87,2%) of the patients had a neurological disease, of which the mean age was 51,05 years and 67,5% were women. The most frequent comorbidities were: hypertension (55,6%); dyslipidemia (20,4%); and diabetes (14,6%). The most common neurological diseases were: Sequelae of Cerebrovascular Disease (12,7%); Unspecified Dementia (8,9%); and Migraine without Aura (7,6%). The main neurological syndromes were: Headache (24,8%); Dementia (15,9%); Cerebrovascular Disease (13,4%); Movement Disorders (12,1%); and Radiculopathy (10,8%). The age and gender profile of these syndromes was further described. These data contribute to better understand the distribution of neurological diseases in the neurological outpatient setting.

The costs of dementia subtypes to California Medicare fee-for-service, 2015

IntroductionDementia is among the costliest of medical conditions, but it is not known how these costs vary by dementia subtype. MethodsThe effect of dementia diagnosis subtype on direct health care costs and utilization was estimated using 2015 California Medicare fee-for-service data. Potential drivers of increased costs in Lewy body dementia (LBD), in comparison to Alzheimer's disease, were tested. Results3,001,987 Medicare beneficiaries were identified, of which 8.2% had a dementia diagnosis. Unspecified dementia was the most common diagnostic category (59.6%), followed by Alzheimer's disease (23.2%). LBD was the costliest subtype to Medicare, on average, followed by vascular dementia. The higher costs in LBD were explained in part by falls, urinary incontinence or infection, depression, anxiety, dehydration, and delirium. DiscussionDementia subtype is an important predictor of health care costs. Earlier identification and targeted treatment might mitigate the costs associated with co-occurring conditions in LBD.

PIH52 DEMENTIA-RELATED PSYCHOSIS: REAL-WORLD PATIENT CHARACTERISTICS AND HEALTHCARE UTILIZATION FROM A LARGE US ADMINISTRATIVE CLAIMS DATABASE

To examine the characteristics and healthcare resource utilization of patients with dementia in the 12 months before diagnosis of dementia-related psychosis (DRP) within a large US health insurer database. Commercial and Medicare Advantage with Part D (MAPD) enrollees aged ≥40 years with evidence of DRP were identified between 01-Jan-2009 and 31-Mar-2017. The first observed indicator of psychosis (≥2 claims-diagnosis or pharmacy fill) co-occurring or following evidence of dementia (≥2 claims-diagnosis or pharmacy fill) was the index date. Continuous enrollment was required from 12 months prior to dementia until index date and 12 months post-index. Patient characteristics were examined in the year prior to the index date. Of 13,006 patients identified, 32.4% had ≥1 diagnosis of “Alzheimer’s Disease,” 28.1% of presenile dementia, senile dementia, or dementia associated with other conditions, and 27.5% of unspecified dementia. Mean age was 80.2 (SD=6.9) years, 67% were female, and 86.3% had MAPD coverage. Mean Charlson Comorbidity Index score was 1.9 (1.9); 76.4% of patients were diagnosed with hypertension, 57.6% with disorders of lipid metabolism, 55.2% with diseases of the urinary system, and 55.3% with diseases of the heart. All-cause utilization was frequent in the year before psychosis occurred: 92.8% of patients had ≥1 office visit (mean # of visits=16.6 [17.2]), 78.1% had ≥1 outpatient visit (8.5 [12.5]) and 58.5% had ≥1 emergency room visit (1.6 [2.9]). Inpatient admissions occurred among 34.6% of patients (0.6 [1.0]) and lasted an average of 12.0 (41.5) days. Mean all-cause total costs were $20,737 ($29,383), with $5,780 ($8,836) spent on pharmacy. The largest portion of medical costs ($14,958 [$27,049]) was from inpatient stays ($7,660 [$22,128]). Patients with DRP were elderly and primarily Medicare beneficiaries. On average, they had low Charlson scores but used health care services more than twice a month in the year before psychosis occurred.

To What Extent Does Age at Death Account for Sex Differences in Rates of Mortality From Alzheimer Disease?

Our objective was to compare sex-specific rates of death with Alzheimer disease (AD) or dementia as the underlying or associated cause of death using death records. Deidentified individual records on causes of death for all people aged 60 years or more who died in Australia during 2006-2014 (n = 1,104,684) were analyzed. There were 184,562 records with International Classification of Diseases, Tenth Revision, codes for dementia (AD, vascular dementia, or unspecified dementia). Death rate ratios for women versus men were estimated using Poisson regression. Women had a greater crude rate of death from all types of dementia than men (5.9 deaths per 1,000 person-years as compared with 3.8 deaths per 1,000 person-years), which disappeared after adjustment for age. For AD, the age-adjusted rate was higher among women (rate ratio = 1.14, 95% confidence interval: 1.12, 1.16), while for vascular dementia age-adjusted rates were higher for men (rate ratio = 0.80, 95% confidence interval: 0.78, 0.82). There was no evidence of a differential bias in coding of dementia type between men and women. Women's older age at death explained much of the sex-related difference in rates of death from AD or dementia. However, excess numbers of AD deaths among women and vascular dementia deaths among men remained, providing support for the hypothesis of greater biological risk of AD in women.

Antipsychotic Treatment Associated With Increased Mortality Risk in Patients With Dementia. A Registry-Based Observational Cohort Study

ObjectiveTo assess all-cause mortality patients with dementia treated with typical and atypical antipsychotic drugs (APDs). DesignRegistry-based cohort study. Setting and participantsA total of 58,412 patients diagnosed with dementia and registered in the Swedish Dementia Registry were included in the study. Of the study sample, 2526 of the patients were prescribed APDs. Of these, 602 patients were prescribed typical APDs and 1833 patients were prescribed atypical APDs. Ninety-one patients were prescribed both typical and atypical APDs. MeasurementsAll-cause mortality based on Swedish Cause of Death Register. Adjusted hazard ratios of mortality were calculated according to class of APDs (typical or atypical) prescribed. Final models were adjusted for age at dementia diagnosis, sex, Charlson comorbidity index, living arrangement, and Mini-Mental State Examination. ResultsIn the adjusted models, use of APDs at the time of dementia diagnosis was associated with increased mortality risk in the total cohort (hazard ratio = 1.4; 95% confidence interval 1.3–1.5). After stratifying for dementia types, increased mortality risks associated with APDs were found in patients with Alzheimer's disease, mixed dementia, unspecified dementia, and vascular dementia. Higher risk for mortality was found with typical APDs in patients with mixed and vascular dementia and with atypical APDs in patients with Alzheimer's disease, mixed, unspecified, and vascular dementia. Furthermore, in patients with Alzheimer's disease who had typical APDs, use lower risk of death emerged in comparison with patients with atypical APDs. Conclusions/ImplicationsBoth the use of atypical and typical APDs increased the risk of death in patients with dementia even after adjusting for differences in basic characteristics between groups. Although we cannot rule out the influence of residual confounding, these results would seem to add to studies suggesting caution in APD prescription for patients with dementia.

Clinical profile of early-onset dementia from a geriatric clinic in South India

Background: Early-onset dementia (EOD) defined as dementia with clinical onset before the age of 65 years, has estimated proportion ranging up to 45.3%. Although EOD leads to severe psychosocial consequences that affect people in their latter part of working age, the literature from India is limited. Objective: The aim of this study is to investigate the profile of patients with EOD attending Geriatric Clinic and Services, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India. Materials and Methodology: All records of patients attending the Geriatric Clinic and Services, diagnosed with EOD between January 2017 and June 2018 with their details pertaining to sociodemographic, clinical, risk factors, and behavioral problems were examined. Results: Of the 320 patients with cognitive complaints seen during the period of 18 months, 108 (33.75%) patients had a diagnosis of EOD. The mean age at onset of illness was 55.38 (Standard deviation - 6.53) years (range - 34–65 years). Of these 58 (53.6%) patients found to have Alzheimer's dementia (AD), 31 (28.7%) have fronto-temporal dementia (FTD), 6 (5.5%) have vascular dementia (VaD), 3 (2.7%) patients have Parkinson's disease-related dementia, and 6 (5.5%) have unspecified dementia. Discussion: During the 18 months, the EOD patients constituted one-third of all dementia patients visiting Geriatric Clinic. Degenerative etiology was the main diagnostic cluster. The most common type was AD, similar to senile type of dementia, was followed by FTD and VaD. The study showed a delay of 3.18 years in seeking consultation. Conclusion: EODs seems to have higher degenerative etiology and with higher associated behavioral and psychological symptoms. There is a need for setting up specialized memory clinics.

Prevalence of Depression, Anxiety and PTSD in People with Dementia: a Systematic Review and Meta-Analysis.

There appears to be a link between depression/anxiety/PTSD and dementia, although the evidence is incomplete and the reason is unclear. Mental illness may cause dementia or may be prodromal or comorbid with dementia, or dementia may trigger a relapse of symptoms in individuals with a history of mental illness. This study examined the link between depression/anxiety/PTSD and dementia by evaluating the prevalence of these disorders in people with dementia, relative to their healthy peers. Existing meta-analyses have examined the prevalence of clinically-significant depression and anxiety in Alzheimer's disease (AD), and depression in frontotemporal dementia (FTD), but have not considered vascular dementia (VaD), dementia with Lewy bodies (DLB), PTSD, or anxiety in FTD. The current meta-analysis compared the prevalence of clinically-significant depression, anxiety and PTSD in the four most common types of dementia (AD, VaD, DLB, FTD) and in unspecified dementia to that of healthy controls (PROSPERO number: CRD42017082086). PubMed, EMBASE, PsycINFO and CINAHL database searches identified 120 eligible studies. Prevalence rates were calculated for depression and anxiety in AD, VaD, DLB, FTD, unspecified dementia, and controls. PTSD data were only available for unspecified dementia. Subgroup analyses indicated that depression, but not anxiety, was more prevalent in people with dementia compared to controls; however, the anxiety analyses were probably under-powered. The results support a link between depression and dementia; however, the link between anxiety or PTSD and dementia remains unclear due to insufficient data. Longitudinal data is now needed to clarify whether depression/anxiety/PTSD may be risk factors for dementia.

DEMENTIA MORTALITY IN THE UNITED STATES, 1999–2016

Background: In 2016, Alzheimer’s disease ranked as the 6th leading cause of death in the United States. Some studies have suggested that the number of deaths due to Alzheimer’s disease could be higher than reported in official mortality statistics, given the diagnostic and reporting challenges associated with dementia. In this research, we present estimates of mortality attributed to dementia, defined as Alzheimer’s disease plus three other dementia causes with similar physical signs and symptoms. The four causes of death examined, based on ICD-10, are Unspecified Dementia (F03), Alzheimer’s disease (G30), Vascular Dementia (F01), and Other Degenerative Diseases of the Nervous System (G31), which includes Lewy Body disease and frontotemporal dementia. We examine the percent distribution of these causes by age, sex, race and Hispanic origin, and state. Trends over time are presented. Results: There were 249,605 deaths attributed to dementia as an underlying cause in 2016: 47% due to Alzheimer’s disease and 40% due to Unspecified Dementia. The prevalence of Alzheimer’s disease and Unspecified Dementia as underlying causes of death varied widely by state and has changed over time. In addition to deaths where dementia is recorded as the underlying cause of death, another 125,195 deaths mentioned dementia as a contributing cause on the death certificate. If all four dementia causes were considered together, dementia would have been the third leading cause of death in the United States in 2016.

192. Preeclampsia and risk of dementia later in life

Introduction Preeclampsia has been linked with later cognitive impairment and brain atrophy, but epidemiologic studies have not confirmed a link with dementia later in life. Objective To explore associations between preeclampsia and later dementia, by dementia subtype and timing of onset. Methods Our study cohort included all women in Denmark with ⩾1 live birth or stillbirth between 1978 and 2015. Using Danish national registers, we identified women who subsequently developed dementia. We used Cox regression to estimate hazard ratios comparing dementia risk among women with and without a history of preeclampsia. Results Our cohort consisted of 1,178,005 women with 20,352,695 person-years of follow-up. Women with a history of preeclampsia had a 53% increase in risk of dementia overall (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.26–1.85) and more than three times the risk of vascular dementia (HR, 3.46; 95% CI, 1.97–6.10) later in life, compared with women with no history of preeclampsia. In contrast, only modest associations were observed for both Alzheimer’s disease (HR 1.45; 95% CI 1.05–1.99) and unspecified dementia (HR, 1.40; 95% CI 1.08–1.83). The association with vascular dementia appeared to be stronger for late-onset disease (age ⩾65 years, HR, 6.53; 95% CI, 2.82–15.1) than for early-onset disease (age Discussion Preeclampsia was associated with an increased risk of dementia, vascular dementia in particular. Cardiovascular disease, hypertension, and diabetes were unlikely to mediate the associations substantially, suggesting that preeclampsia and vascular dementia may share underlying mechanisms or susceptibility pathways.

Survival and years of life lost in various aetiologies of dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD) in Norway.

IntroductionAlzheimer’s disease patients are reported to have higher survival rate compared to patients with vascular dementia or dementia with Lewy bodies. There is a paucity of studies investigating survival including persons with cognitive decline and dementia of various aetiologies.ObjectivesWe aimed to compare survival for patients with subjective cognitive decline, mild cognitive impairment, Alzheimer’s disease, vascular dementia, mixed Alzheimer’s/vascular dementia, dementia with Lewy bodies/Parkinson’s disease, and other dementias compared to the general Norwegian population, taking into account the role of gender, cognitive function, function in everyday activities, comorbidity and education.MethodsPatients (N = 4682), ≥65 years, in the The Norwegian register of persons assessed for cognitive symptoms (NorCog) during 2009–2017 were followed for mortality in the National Registry until January 2018. Flexible parametric survival models were applied to estimate relative survival, life expectancy and years of life lost for diagnostic groups compared with the general population.ResultsPatients with vascular dementia or dementia with Lewy bodies/Parkinson’s had the shortest survival, followed by mixed dementia, Alzheimer’s disease, unspecified dementia, mild cognitive impairment and subjective cognitive decline. At age 70 years, men with vascular dementia or dementia with Lewy bodies/Parkinson’s had life expectancy of 4.7 years, which corresponded to 10.3 years of life lost compared to the general population. Years of life lost for other diagnoses were 10.0 years for mixed dementia, 9.2 years for Alzheimer’s disease, 9.3 years for other dementias, 5.2 years for mild cognitive impairment and 2.2 years for subjective cognitive decline. Corresponding years of life lost in women were: 12.7 years, 10.5 years, 9.8 years, 10.6 years, 7.8 years, and 2.6 years. Poor relative survival among dementia patients was associated with male gender, comorbidity, low cognitive function, and low function in activities of daily living.ConclusionsCompared with the general population, patients with subjective cognitive decline had no significant loss in life expectancy, while patients with mild cognitive impairment and all dementia subtypes had large losses, especially those with a diagnosis of vascular dementia or dementia with Lewy bodies/Parkinson’s.

Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study.

Dementia is a major cause of disability, and risk-factor reduction may have the potential to delay or prevent the disease. Our aim was to determine the absolute 10-year risk of dementia, by age, sex and apolipoprotein E (APOE) genotype. We obtained data from the Copenhagen General Population Study (from 2003 to 2014) and the Copenhagen City Heart Study (from 1991 to 1994 and 2001 to 2003). Participants underwent a questionnaire, physical examination and blood sampling at baseline. Diagnoses of dementia and cerebrovascular disease were obtained from the Danish National Patient Registry up to Nov. 10, 2014. Among 104 537 individuals, the absolute 10-year risk of Alzheimer disease in 3017 women and men who were carriers of the APOE ɛ44 genotype was, respectively, 7% and 6% at age 60-69 years, 16% and 12% at age 70-79 years, and 24% and 19% at age 80 years and older. Corresponding values for all dementia were 10% and 8%, 22% and 19%, and 38% and 33%, respectively. Adjusted hazard ratios (HRs) for all dementia increased by genotype, from genotype ɛ22 to ɛ32 to ɛ33 to ɛ42 to ɛ43 to ɛ44 (p for trend < 0.001). Compared with ɛ33 carriers, ɛ44 carriers were more likely to develop Alzheimer disease (adjusted HR 8.74, 95% confidence interval [CI] 7.08-10.79), vascular dementia (adjusted HR 2.87, 95% CI 1.54-5.33), unspecified dementia (adjusted HR 4.68, 95% CI 3.74-5.85) and all dementia (adjusted HR 5.77, 95% CI 4.89-6.81). Age, sex and APOE genotype robustly identify high-risk groups for Alzheimer disease and all dementia. These groups can potentially be targeted for preventive interventions.

Clinical exome sequencing in dementias: a preliminary study.

Dementias are clinically and genetically heterogeneous group of neurodegenerative disorders. Often, dementias with genetic etiology are clinically indistinguishable from non-genetic ones. The aim of this retrospective study was to evaluate the yield of clinical exome sequencing in dementias, potentially associated with monogenic genetic predisposition. For this purpose 20 consecutive patients younger than 65 years were studied in the period from January 2014 to December 2017; 14 with the diagnosis of Frontotemporal dementia (FTD), 3 with early-onset Alzheimer disease (EOAD) and 3 with unspecified dementia. In addition to clinical exome sequencing including 57 genes associated with dementia, C9orf72 hexanucleotide expansion as tested in all patients. We found genetic etiology in 6 patients: 2 mutations in the PSEN1 gene (p.Pro264Ser and p.Phe105Cys) in the EOAD patients, C9orf72 expansion and MAPT (c.1920+16C>T), mutation in the FTD group of patients as well as MAPT (c.1920+16C>T) mutation and likely pathogenic mutation in the TYROBP mutation (p.Asp32Asn) in patients with unspecified diagnosis. Our preliminary results imply significant diagnostic yield in identifying rare genetic causes of dementia, combining comprehensive clinical exome sequencing and targeted C9orf72 expansion testing.

한양방 협진치료를 받은 치매와 경도인지장애 환자에 대한 후향적 의무기록 분석

Objectives: To investigate the characteristics of patients diagnosed with dementia or mild cognitive impairment who are treated by means of a blend between Western and Korean medicine. Methods: We searched for outpatients with dementia or mild cognitive impairment by means of a collaboration between Western and Korean medicine from August 1, 2015, to July 31, 2017, through electronic medical records in Wonkwang Hospital. The records were retrospectively analyzed according to the patients’ demographic and clinical characteristics, pathway of medical care, diagnostic tests, treatment, and medical expenses. Results: Thirteen patients were included in the analysis. Among them, six patients were diagnosed with mild cognitive impairment, five with dementia, Alzheimer''s type, one patient with frontotemporal dementia, and one patient with unspecified dementia. Twelve of the thirteen patients were over 60 years of age. The number of pathways from the Dept. of Neurology to the Dept. of Neuropsychiatry of Korean Medicine was almost the same as the opposite pathway. The most used diagnostic test in Korean medicine was a neuropsychological test such as SNSB, MMSE and GDS. In Western medicine, hematology and neuroimaging were frequently used for patients. Acupuncture in Korean medicine and medication in Western medicine were the most frequently used. In Korean medicine, uncovered service costs were much higher than covered service costs,. whereas, in Western medicine, covered service costs were higher than uncovered service costs. Conclusions: This study describes the basic characteristics of dementia and mild cognitive impairment patients treated by a collaboration between Western and Korean medicine. Based on these results, a clinical pathway of the collaborative practice system between Western and Korean medicine for dementia patients needs to be developed.

Increased risk of dementia in patients with Schizophrenia: A population-based cohort study in Taiwan

BackgroundThe extent to which schizophrenia is associated with the risk of all-cause dementia is controversial. This study investigated the risk of dementia by type in patients with schizophrenia. MethodsData were collected from the Taiwanese National Health Insurance Database 2005 and analyzed using multivariate Cox proportional hazard regression models to determine the effect of schizophrenia on the dementia risk after adjusting for demographic characteristics, comorbidities, and medications. Fine and Gray's competing risk analysis was used to determine the risk of dementia, as death can act as a competing risk factor for dementia. ResultsWe assessed 6040 schizophrenia patients and 24,160 propensity scale-matched control patients. Schizophrenia patients exhibited a 1.80-fold risk of dementia compared to controls (adjusted hazard ratio [aHR] = 1.80, 95% confidence interval [CI] = 1.36 ∼ 2.21, p < 0.001) after adjusting for covariates. Cardiovascular disease (aHR = 5.26; 95% CI = 4.50 ∼ 6.72; p < 0.001), hypertension (aHR = 1.83; 95% CI = 1.77 ∼ 2.04; p = 0.002), traumatic head injury (aHR = 1.35; 95% CI = 1.24 ∼ 1.78; p < 0.001), chronic lung diseases (aHR = 1.64; 95% CI = 1.13 ∼ 2.56; p < 0.001), alcohol-related disorders (aHR = 3.67; 95% CI = 2.68 ∼ 4.92; p < 0.001), and Parkinson’s disease (aHR = 1.72; 95% CI = 1.25 ∼ 2.40; p < 0.001) were significantly associated with dementia risk. Notably, first-generation antipsychotics (aHR = 0.80; 95% CI = 0.56 ∼ 0.95; p = 0.044) and second-generation antipsychotics (aHR = 0.24; 95% CI = 0.11 ∼ 0.60; p < 0.001) were associated with a lower dementia risk. Sensitivity tests yielded consistent findings after excluding the first year and first 3 years of observation. Patients with schizophrenia had the highest risk of developing Alzheimer’s [dementia/disease?] among dementia subtypes (aHR = 2.10; 95% CI = 1.88 ∼ 3.86; p < 0.001), followed by vascular dementia (aHR = 1.67; 95% CI = 1.27 ∼ 2.12; p < 0.001) and unspecified dementia (aHR = 1.30; 95% CI = 1.04 ∼ 2.01; p < 0.001). ConclusionsSchizophrenia was significantly associated with the risk of all-cause dementia. Data are scarce on the mechanisms through which antipsychotic agents protect persons with schizophrenia from developing dementia. Further research is recommended to elucidate the neurobiological mechanisms underlying the association between schizophrenia and dementia, and whether antipsychotics protect against the development of dementia in schizophrenia.

Clinical variability and onset age modifiers in an extended Belgian GRN founder family.

We previously reported a granulin (GRN) null mutation, originating from a common founder, in multiple Belgian families with frontotemporal dementia. Here, we used data of a 10-year follow-up study to describe in detail the clinical heterogeneity observed in this extended founder pedigree. We identified 85 patients and 40 unaffected mutation carriers, belonging to 29 branches of the founder pedigree. Most patients (74.4%) were diagnosed with frontotemporal dementia, while others had a clinical diagnosis of unspecified dementia, Alzheimer's dementia or Parkinson's disease. The observed clinical heterogeneity can guide clinical diagnosis, genetic testing, and counseling of mutation carriers. Onset of initial symptomatology is highly variable, ranging from age 45 to 80years. Analysis of known modifiers, suggested effects of GRN rs5848, microtubule-associated protein tau H1/H2, and chromosome 9 open reading frame 72 G4C2 repeat length on onset age but explained only a minor fraction of the variability. Contrary, the extended GRN founder family is a valuable source for identifying other onset age modifiers based on exome or genome sequences. These modifiers might be interesting targets for developing disease-modifying therapies.

A Literature Review of Methodologies Used in Randomized Clinical Trials of Agitation in Alzheimer's Disease.

Agitation is a common and burdensome symptom associated with Alzheimer's disease (AD). This is a narrative literature review of the designs and methods used in randomized clinical trials of agitation in patients with AD; sources range from published, to completed but not published, to ongoing studies in the past 10 years. Selection for review included blinded, randomized trials conducted to assess the effect of a pharmacological intervention for which agitation in patients with AD was among the prespecified end points. Key criteria for exclusion included open-label studies, trials of dementia not specific to AD, or mixed populations of AD and unspecified dementia. A search of PubMed and clinicaltrials.gov databases identified 36 trials for which agitation was among the prespecified end points: 18 were published trials and 18 were completed but not published or ongoing. There was significant heterogeneity among AD studies in terms of diagnostic criteria, assessment of severity of disease and agitation, sample size and powering assumptions, treatment duration, patient age and cognitive status, and outcomes measurements. Few studies used a mitigation strategy for placebo response. Accumulating evidence suggests that it is important to consider the following in trial design: thresholds for baseline severity of agitation and AD; use of prespecified accepted criteria to define agitation; and use of standardized, validated tools to measure treatment effects during a trial. Adoption of these design strategies might help improve signal detection and bring us closer to identifying the most appropriate, effective, and safe treatments for agitation in patients with AD.

End stage renal disease is associated with development of dementia.

There is controversy regarding the extent of risk for dementia in patients with end stage renal disease (ESRD) who are undergoing hemodialysis (HD) or peritoneal dialysis (PD). We examined data from Taiwan's Longitudinal Health Insurance Database, and used Cox proportional hazard regression analysis to compare the development of dementia in 72,934 HD and PD patients with 72,934 matched controls from January 1, 1999 to December 31, 2010. The results indicate an increased risk for dementia overall in HD patients (adjusted hazard ratio [aHR] = 1.64, p < 0.0001) and PD patients (aHR = 2.21, p < 0.0001). HD and PD patients also had significantly greater aHRs for vascular dementia (VaD) and unspecified dementia (UnD), but only HD patients had a significantly greater aHR for Alzheimer's disease (AD). Further research is needed to confirm whether management of ESRD with PD can reduce the incidence of AD, and to identify the mechanisms by which ESRD increases the risk of dementia.

Cannabinoids for the treatment of dementia

Background Dementia is a common chronic condition, mainly affecting older adults, characterised by a progressive decline in cognitive and functional abilities. Medical treatments for dementia are limited. Cannabinoids are being investigated for the treatment of dementia. Objectives To determine the efficacy and safety of cannabinoids for the treatment of dementia. Search methods We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialised Register - on 8 July 2021, using the terms cannabis or cannabinoid or endocannabinoid or cannabidiol or THC or CBD or dronabinol or delta-9-tetrahydrocannabinol or marijuana or marihuana or hashish. The register contains records from all major healthcare databases (the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS), as well as from many clinical trials registries and grey literature sources. Selection criteria We included all randomised controlled trials (RCTs) of cannabinoids for the treatment of dementia. We included participants of any age and of either sex with diagnosed dementia of any subtype, or with unspecified dementia of any severity, from any setting. We considered studies of cannabinoids administered by any route, at any dose, for any duration, compared with placebo, no treatment, or any active control intervention. Data collection and analysis Two review authors independently screened and selected studies for inclusion, extracted data, and assessed the risk of bias in included studies. When necessary, other review authors were involved in reaching consensus decisions. We conducted meta-analyses using a generic inverse variance fixed-effect model to derive estimates of effect size. We used GRADE methods to assess our confidence in the effect estimates. Main results We included four studies (126 participants) in this review. Most participants had Alzheimer's disease; a few had vascular dementia or mixed dementia. Three studies had low risk of bias across all domains; one study had unclear risk of bias for the majority of domains. The included studies tested natural delta-9-tetrahydrocannabinol (THC) (Namisol) and two types of synthetic THC analogue (dronabinol and nabilone). Three trials had a cross-over design. Interventions were applied over 3 to 14 weeks; one study reported adverse events over 70 weeks of follow-up. One trial was undertaken in the USA, one in Canada, and two in The Netherlands. Two studies reported non-commercial funding, and two studies were conducted with the support of both commercial and non-commercial funding. Primary outcomes in this review were changes in global and specific cognitive function, overall behavioural and psychological symptoms of dementia (BPSD), and adverse events. We found very low-certainty evidence suggesting there may be little or no clinically important effect of a synthetic THC analogue on cognition assessed with the standardised Mini-Mental State Examination (sMMSE) (mean difference (MD) 1.1 points, 95% confidence interval (CI) 0.1 to 2.1; 1 cross-over trial, 28 participants). We found low-certainty evidence suggesting there may be little or no clinically important effect of cannabinoids on overall behavioural and psychological symptoms of dementia assessed with the Neuropsychiatric Inventory (or its modified nursing home version) (MD -1.97, 95% CI -3.87 to -0.07; 1 parallel group and 2 cross-over studies, 110 participants). All included studies reported data on adverse events. However, the total number of adverse events, the total numbers of mild and moderate adverse events, and the total number of serious adverse events (SAEs) were not reported in a way that permitted meta-analysis. There were no clear differences between groups in numbers of adverse events, with the exception of sedation (including lethargy), which was more frequent among participants taking nabilone (N = 17) than placebo (N = 6) (odds ratio (OR) 2.83, 95% CI 1.07 to 7.48; 1 cross-over study, 38 participants). We judged the certainty of evidence for adverse event outcomes to be low or very low due to serious concerns regarding imprecision and indirectness. Authors' conclusions Based on data from four small, short, and heterogeneous placebo-controlled trials, we cannot be certain whether cannabinoids have any beneficial or harmful effects on dementia. If there are benefits of cannabinoids for people with dementia, the effects may be too small to be clinically meaningful. Adequately powered, methodologically robust trials with longer follow-up are needed to properly assess the effects of cannabinoids in dementia.

Prevalence of Use of Cardiovascular Drugs in Dementia Patients Treated in General Practices in Germany

Dementia is a chronic disease associated with numerous cardiovascular disorders. To analyze the prevalence of cardiovascular drug use in dementia patients treated in general practices in Germany. The present study included patients who were diagnosed with dementia (Alzheimer's disease, vascular dementia, or unspecified dementia) in 2015. The main outcome measure was the proportion of patients using cardiovascular drugs. Demographical and clinical variables included age, sex, dementia type, and cardiovascular co-diagnoses. A multivariate logistic regression model was used to analyze the association between cardiovascular drug use and these variables. We identified 7,987 and 1,268 dementia patients with and without prescriptions for cardiovascular drugs, respectively. The share of individuals who received cardiovascular treatments was 86.3%. Diuretics (20.9%), beta blocking agents (20.0%), and ACE inhibitors (17.4%) were the three most commonly prescribed types of medications. Patients between the ages of 71-80 (OR = 1.59), 81-90 (OR = 1.61), and over 90 years (OR = 1.48) were more likely to receive cardiovascular drugs than patients under the age of 70 years. Moreover, compared to those with unspecified dementia, individuals with Alzheimer's disease had a lower chance while those with vascular dementia had a higher chance of being prescribed these drugs (ORs equal to 0.81 and 1.22, respectively). Finally, we found a positive association between the use of cardiovascular drugs and all co-diagnoses (ORs ranging from 1.23 to 7.12). The prevalence of cardiovascular drug use in dementia patients was around 86%. This use was significantly associated with such factors as age, type of dementia, and co-diagnoses.