Late-onset Dementia Research Articles

Associations of combined accelerated biological aging and genetic susceptibility with incident dementia: a prospective study in the UK Biobank

BackgroundAccelerated biological aging has been verified to be a critical risk factor for a number of age-related diseases, but its role in dementia remained unclear. Whether it modified the effects of genetic factors was also unknown. This study evaluated the associations between accelerated biological aging and dementia and the moderating role of accelerated biological aging in the genetic susceptibility to the disease.MethodsWe included 200,731 participants in the UK biobank. Nine clinical blood biomarkers and chronological age were used to calculate Phenotypic age acceleration (PhenoAgeAccel), which is a novel indicator for accelerated biological aging. The associations of PhenoAgeAccel with dementia, both young-onset and late-onset dementia, were assessed by Cox proportional hazard models. Apolipoprotein E (APOE) alleles and polygenic risk scores (PRS) were used to evaluate the genetic risk of dementia. The interactions between genetic susceptibility and biological aging were tested on both multiplicative and additive scales.ResultsThese findings showed individuals who were in the highest quartile of PhenoAgeAccel had a higher risk with incidence of dementia compared to individuals in the lowest quartile of PhenoAgeAccel (HR: 1.145 (95% CI: 1.050, 1.249)). Individuals with biologically older had a higher risk of dementia than individuals with biologically younger (HR: 1.069 (95% CI: 1.004, 1.138)). Furthermore, compared to individuals with biologically younger and low APOE ε4-related genetic risk, individuals with biologically younger and high APOE ε4-related genetic risk (HR:3.048 (95% CI: 2.811, 3.305)) had a higher risk of dementia than individuals with biologically older and high APOE ε4-related genetic risk (HR: 2.765 (95% CI: 2.523, 3.029)). Meanwhile, referring to low dementia PRS and biologically younger, the risk of dementia increased by 72.7% (HR: 1.727 (95% CI: 1.538, 1.939) in the biologically younger and high PRS group and 58.7% (HR: 1.587 (95% CI: 1.404, 1.793) in the biologically older and high PRS group, respectively. The negative interactions between PhenoAgeAccel with APOE ε4 and PRS were also tested on the additive scale.ConclusionsAccelerated biological aging could bring the extra risk of dementia but attenuate the effects of genetic risk on dementia. These findings provide insights for precise prevention and intervention of dementia.

Whole genome methylation sequencing in blood from persons with mild cognitive impairment and dementia due to Alzheimer's disease identifies cognitive status.

Whole genome methylation sequencing (WGMS) in blood identifies differential DNA methylation in persons with late-onset dementia due to Alzheimer's disease (AD) but has not been tested in persons with mild cognitive impairment (MCI). We used WGMS to compare DNA methylation levels at 25,244,219 CpG loci in 382 blood samples from 99 persons with MCI, 109 with AD, and 174 who are cognitively unimpaired (CU). WGMS identified 9,756 differentially methylated positions (DMPs) in persons with MCI, including 1,743 differentially methylated genes encoding proteins in biological pathways related to synapse organization, dendrite development, and ion transport. 447 DMPs exhibit progressively increasing or decreasing DNA methylation levels between CU, MCI, and AD that correspond to cognitive status. WGMS identifies DMPs in known and newly detected genes in blood from persons with MCI and AD that support blood DNA methylation levels as candidate biomarkers of cognitive status.

Association of adherence to the EAT-Lancet diet with risk of dementia according to social economic status: a prospective cohort in UK Biobank.

The EAT-Lancet Commission has proposed a reference diet aiming to promote human health and environmental sustainability. Socioeconomic disadvantage and poor diet are well-known risk factors for dementia; however, whether the effect of this reference diet on dementia varies by socioeconomic status has not been investigated. The dietary habits of 190,893 participants from UK-Biobank were assessed; the association of EAT-Lancet diet with incident dementia across socioeconomic status was determined by Cox models. One thousand seven hundred twenty-eight dementia cases were identified during a median of 12.24 years follow-up. An inverse association between adherence to EAT-Lancet diet and all-cause dementia (high vs. low; hazard ratio [HR], 95% confidence interval [CI]: 0.82, 0.72-0.94) or late-onset dementia (high vs. low; HR, 95% CI: 0.78, 0.68-0.91) was observed only in individuals with high socioeconomic status. On the contrary, no protective effects of EAT-Lancet diet on early-onset dementia were observed, regardless of the socioeconomic status. Our findings indicated that adherence to an environment-friendly diet helps attenuate risk of dementia only in individuals with high socioeconomic level.

Characteristics of Alzheimer’s Disease and Mild Cognitive Impairment Influenced by the Time of Onset

Introduction: Although the prevalence of Alzheimer’s disease (AD) is higher in older people compared to younger people, dementia has also been documented in younger adults. Although early-onset dementia and late-onset dementia had been considered a single disease in pathological investigations, many studies revealed differences in cognitive and neuroimaging changes between them. We evaluated differences in cognitive and neuroimaging changes among the following groups: individuals with early-onset AD (EOAD), late-onset AD (LOAD), early-onset mild cognitive impairment (EOMCI), or late-onset MCI (LOMCI), and healthy controls (HCs). Methods: Patients underwent both a 1.5 Tesla magnetic resonance imaging scan and the Mini-Mental State Examination (MMSE). Differences in regional gray matter volumes and MMSE subscales were investigated among the five diagnostic groups. Results: Compared to the EOAD group, the LOAD group had significantly higher scores on orientation in place. Compared to the LOMCI patients, the EOMCI patients achieved significantly higher recall scores. The LOAD and LOMC groups showed significant volume reductions in bilateral medial temporal regions compared to the HCs. The EOAD and EOMCI groups did not show significant atrophy of the medial temporal region compared to the HC group. Conclusions: The hippocampal volume and memory were preserved in the patients with EOMCI or EOAD compared to those with LOMCI or LOAD. These findings may indicate that the distinct and differing patterns of neuropsychological changes between EOAD and LOAD are also common in MCI, which is intermediate between normal cognition and AD.

Exposure to Lead in Drinking Water Causes Cognitive Impairment via an Alzheimer's Disease Gene-Dependent Mechanism in Adult Mice.

Exposure to lead (Pb) is a major public health problem that could occur through contaminated soil, air, food, or water, either during the course of everyday life, or while working in hazardous occupations. Although Pb has long been known as a neurodevelopmental toxicant in children, a recent and growing body of epidemiological research indicates that cumulative, low-level Pb exposure likely drives age-related neurologic dysfunction in adults. Environmental Pb exposure in adulthood has been linked to risk of late-onset Alzheimer's disease (AD) and dementia. Although the biological mechanism underlying this link is unknown, it has been proposed that Pb exposure may increase the risk of AD via altering the expression of AD-related genes and, possibly, by activating the molecular pathways underlying AD-related pathology. We investigated Pb exposure using a line of genetically modified mice with AD-causing knock-in mutations in the amyloid precursor protein and presenilin 1 (APPΔNL/ΔNL x PS1P264L/P264L) that had been crossed with Leprdb/db mice to impart vulnerability to vascular pathology. Our data show that although Pb exposure in adult mice impairs cognitive function, this effect is not related to either an increase in amyloid pathology or to changes in the expression of common AD-related genes. Pb exposure also caused a significant increase in blood pressure, a well known effect of Pb. Interestingly, although the increase in blood pressure was unrelated to genotype, only mice that carried AD-related mutations developed cognitive dysfunction, in spite of showing no significant change in cerebrovascular pathology. These results raise the possibility that the increased risk of dementia associated with Pb exposure in adults may be tied to its subsequent interaction with either pre-existing or developing AD-related neuropathology.

A new model to understand the complexity of inequalities in dementia

Many people living with dementia and unpaid carers experience inequalities in care related to challenges in receiving a correct diagnosis, care and support. Whilst complexities of the evidence are well recognised including barriers in receiving a diagnosis or post-diagnostic care, no coherent model has captured the far-reaching types and levels of inequalities to date. Building on the established Dahlgren & Whitehead Rainbow model of health determinants, this paper introduces the new Dementia Inequalities model. The Dementia Inequalities model, similar to the original general rainbow model, categorises determinants of health and well-being in dementia into three layers: (1) Individual; (2) Social and community networks; and (3) Society and infrastructure. Each layer comprises of general determinants, which have been identified in the original model but also may be different in dementia, such as age (specifically referring to young- versus late-onset dementia) and ethnicity, as well as new dementia-specific determinants, such as rare dementia subtype, having an unpaid carer, and knowledge about dementia in the health and social care workforce. Each layer and its individual determinants are discussed referring to existing research and evidence syntheses in the field, arguing for the need of this new model. A total of 48 people with lived, caring, and professional experiences of dementia have been consulted in the process of the development of this model. The Dementia Inequalities model provides a coherent, evidence-based overview of inequalities in dementia diagnosis and care and can be used in health and social care, as well as in commissioning of care services, to support people living with dementia and their unpaid carers better and try and create more equity in diagnosis and care.

Young onset dementia and driving cessation: a scoping review of lived experiences

BackgroundDriving cessation is one of the most challenging life transitions, associated with multiple negative consequences for individuals living with late-onset dementia. This paper extends the literature as to date there is no published review that details the experiences of people living with young onset dementia (“YOD”).MethodsA comprehensive search of the literature was conducted using the scoping review methodology.ResultsTen studies were included for full text review of 1634 initially identified through database searching. The results of the included articles indicated areas of concern for people living with YOD and their family members including, loss of independence; role change; threat to self-identify; feelings of isolation, grief; acceptance; predictors of driving cessation.ConclusionThere is a lack of robust evidence related to driving cessation and the experiences of people living with YOD. No published paper reported psychosocial interventions specifically targeted at supporting persons with YOD through driving cessation.

Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease.

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals. The comorbidity of the two neurological disorders represents a grave health threat to older populations. This review presents a brief background of the development of novel concepts and their clinical potentials. The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca 2+ influx is critical for neuronal function. An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca 2+ mainly via N-methyl-D-aspartate receptors, particularly of those at the extrasynaptic site. This Ca 2+ -evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity. Furthermore, mild but sustained Ca 2+ increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic, but gradually set off deteriorating Ca 2+ -dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways. Based on the Ca 2+ hypothesis of Alzheimer's disease and recent advances, this Ca 2+ -activated "silent" degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis. The N-methyl-D-aspartate receptor subunit GluN3A, primarily at the extrasynaptic site, serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity. Ischemic stroke and Alzheimer's disease, therefore, share an N-methyl-D-aspartate receptor- and Ca 2+ -mediated mechanism, although with much different time courses. It is thus proposed that early interventions to control Ca 2+ homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia. This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.

Essential New Complexity-Based Themes for Patient-Centered Diagnosis and Treatment of Dementia and Predementia in Older People: Multimorbidity and Multilevel Phenomenology.

Dementia is a highly prevalent condition with devastating clinical and socioeconomic sequela. It is expected to triple in prevalence by 2050. No treatment is currently known to be effective. Symptomatic late-onset dementia and predementia (SLODP) affects 95% of patients with the syndrome. In contrast to trials of pharmacological prevention, no treatment is suggested to remediate or cure these symptomatic patients. SLODP but not young onset dementia is intensely associated with multimorbidity (MUM), including brain-perturbating conditions (BPCs). Recent studies showed that MUM/BPCs have a major role in the pathogenesis of SLODP. Fortunately, most MUM/BPCs are medically treatable, and thus, their treatment may modify and improve SLODP, relieving suffering and reducing its clinical and socioeconomic threats. Regrettably, the complex system features of SLODP impede the diagnosis and treatment of the potentially remediable conditions (PRCs) associated with them, mainly due to failure of pattern recognition and a flawed diagnostic workup. We suggest incorporating two SLODP-specific conceptual themes into the diagnostic workup: MUM/BPC and multilevel phenomenological themes. By doing so, we were able to improve the diagnostic accuracy of SLODP components and optimize detecting and favorably treating PRCs. These revolutionary concepts and their implications for remediability and other parameters are discussed in the paper.

Do I Have Symptoms of Dementia: A Discursive Study of Awareness and Shame Among People With Advanced Dementia.

This study explores the narrated experiences of individuals with advanced stages of late-onset dementia, focusing on their diagnosis awareness. Such framing is motivated by 2 reasons. Firstly, there is a lack of consensus regarding the prevalence of anosognosia among people with dementia. Secondly, research on anosognosia often neglects to address the important issues of shame and stigma associated with receiving a dementia diagnosis. For this qualitative study, a total of 27 participants ranging in age from 66 to 94 were involved. The data collected were analyzed using textual-oriented discourse analysis. Our findings indicated that individuals with dementia struggled to comprehend the medical terminology used to describe their experiences within biomedical standards. The interviewees utilized 5 negative discourses on dementia, which shaped their attitudes toward the condition and people diagnosed with it. These discourses depicted dementia as an illness, negative aging, a devaluation, a burden, and a life tragedy. Moreover, study participants did not outright reject the diagnosis but rather negotiated its acceptance within the context of shame associated with dementia. The concept of anosognosia can serve as a mechanism of social control and stigmatization of people with dementia within the dominant biomedical discourse.

Young-onset dementia: not the same as late-onset dementia – highlighting the differences in diagnosis, care, treatment, and models of care

Young-onset dementia: not the same as late-onset dementia – highlighting the differences in diagnosis, care, treatment, and models of care

Atrial Fibrillation and Other Cardiovascular Factors and the Risk of Dementia: An Italian Case-Control Study.

Dementia is a major neurologic syndrome characterized by severe cognitive decline, and it has a detrimental impact on overall physical health, leading to conditions such as frailty, changes in gait, and fall risk. Depending on whether symptoms occur before or after the age of 65, it can be classified as early-onset (EOD) or late-onset (LOD) dementia. The present study is aimed at investigating the role of cardiovascular factors on EOD and LOD risk in an Italian population. Using a case-control study design, EOD and LOD cases were recruited at the Modena Cognitive Neurology Centers in 2016-2019. Controls were recruited among caregivers of all the dementia cases. Information about their demographics, lifestyles, and medical history were collected through a tailored questionnaire. We used the odds ratio (OR) and 95% confidence interval (CI) to estimate the EOD and LOD risk associated with the investigated factors after adjusting for potential confounders. Of the final 146 participants, 58 were diagnosed with EOD, 34 with LOD, and 54 were controls. According to their medical history, atrial fibrillation was associated with increased disease risk (ORs 1.90; 95% CI 0.32-11.28, and 3.64; 95% CI 0.32-41.39 for EOD and LOD, respectively). Dyslipidemia and diabetes showed a positive association with EOD, while the association was negative for LOD. We could not evaluate the association between myocardial infarction and EOD, while increased risk was observed for LOD. No clear association emerged for carotid artery stenosis or valvular heart disease. In this study, despite the limited number of exposed subjects and the high imprecision of the estimates, we found positive associations between cardiovascular disease, particularly dyslipidemia, diabetes, and atrial fibrillation, and EOD.

Effects of risk factors on the development and mortality of early- and late-onset dementia: an 11-year longitudinal nationwide population-based cohort study in South Korea

BackgroundEarly-onset dementia (EOD, onset age < 65) and late-onset dementia (LOD, onset age ≥ 65) exhibit distinct features. Understanding the risk factors for dementia development and mortality in EOD and LOD respectively is crucial for personalized care. While risk factors are known for LOD development and mortality, their impact on EOD remains unclear. We aimed to investigate how hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, and osteoporosis influence the development and mortality of EOD and LOD, respectively.MethodsUsing the Korean National Health Insurance Service (NHIS) database, we collected 546,709 dementia-free individuals and followed up for 11 years. In the two study groups, the Younger group (< 65 years old) and the Older group (≥ 65 years old), we applied Cox proportional hazard models to assess risk factors for development of EOD and LOD, respectively. Then, we assessed risk factors for mortality among EOD and LOD.ResultsDiabetes mellitus and osteoporosis increased the risk of EOD and LOD development. Hypertension increased the risk of EOD, while atrial fibrillation increased the risk of LOD. Conversely, hyperlipidemia exhibited a protective effect against LOD development. Additionally, diabetes mellitus increased mortality in EOD and LOD. Hypertension and atrial fibrillation increased mortality in LOD, while hyperlipidemia decreased mortality in EOD and LOD.ConclusionsRisk factors influencing dementia development and mortality differed in EOD and LOD. Targeted public health interventions addressing age-related risk factors may reduce dementia incidence and mortality.

Insights into Early Onset Dementia: a protocol for an 8-year nationwide retrospective study using administrative data

IntroductionEarly-onset dementia (EOD) is defined as any type of dementia with an onset before the age of 65. Despite its profound impact on patients and their families, EOD has garnered less attention when compared to late-onset dementia (LOD), often resulting in its underestimation. In comparison to LOD, EOD commonly manifests with atypical and heterogeneous symptoms, encompassing mainly non-memory problems, ranging from language and executive impairments to behavioral-led dysfunction. Despite the importance of accurate data to organize appropriate healthcare, evidence regarding EOD patients in Portugal is lacking.ObjectivesThe primary aims of this study include identifying the causes for hospitalization in EOD patients, diagnosed with dementia either as a primary or secondary diagnosis, and comparing them with inpatients aged 65 and older (LOD). Additionally, the study aims to analyze key hospitalization outcomes for both groups, including length of stay, in-hospital mortality, and readmissions. As a secondary aim, this study seeks to describe subtypes of EOD.MethodsA retrospective observational study will be conducted following the RECORD statement. Data will be retrieved from an administrative database that gathers de-identified routinely collected hospitalization data from all Portuguese mainland public hospitals. Hospitalization episodes of inpatients younger than 65 years old, with a primary or secondary diagnosis of dementia (ascertained by ICD-9-CM codes 290.0-290.4, 294.0-294.2, 331.0, 331.1, and 331.82), will be extracted. Comparison patients will be selected by propensity score-matching from inpatients over 65 years with a dementia ICD-9-CM code (in any position), matched for Charlson Comorbidity Index (CCI).ResultsDescriptive and analytical statistics will be conducted to describe and characterize both group of inpatients. Variables such as age at admission, sex, place of residence, causes and type of admission, psychiatric comorbidities, length of stay (LoS), destination after discharge, readmissions, in-hospital mortality and hospital charges will be analyzed.ConclusionsWith this nationwide analysis of EOD hospitalizations, we aim to reveal critical aspects of this condition, including common causes of admission, diagnostic features and health outcomes, allowing for appropriate medical interventions and support tailored to the specific needs of this clinical group.Disclosure of InterestNone Declared

Late Onset Suicide and Dementia

Late Onset Suicide and Dementia

Navigating Neurocognitive Territory: Late-Onset Bipolar Disorder Insights

IntroductionAffective disorders are associated with cognitive deterioration, manifested by an increased risk of developing dementia. Late-onset bipolar disorder (BD) establishes a dynamic interaction between dementia and BD, considering its particular manifestations in old age.ObjectivesProvide a comprehensive overview of the clinical and epidemiological attributes specific to late-onset BD, elucidating its interplay with dementia.Methods We conducted a literature search on PubMed in August 2023, using the following terms: late-onset bipolar disorder AND dementia. Only systematic reviews and meta-analysis were included with no year or language restrictions. Three articles were eligible for this review: two systematic reviews and one meta-analysis.ResultsLate-onset BD can be defined as a secondary condition and may result from an expression of lower vulnerability to BD, when compared to early-onset BD. On the other hand, late-onset BD may be conceptualized as a subtype of pseudodementia, or even considered a risk factor for dementia. In fact, this particular association with dementia supports the existence of a specific class of BD, i.e. BD type VI. Such diagnostic overlap might be explained by common factors that have been associated with both BD and dementia, such as cardiovascular risk factors, systemic inflammation, stress and levels of baseline cognitive reserve. Despite the commonalities, other aspects, such as family history and prior history of a mood disorder, may help to make the differential diagnosis between late-onset BD and dementia.ConclusionsThere is a diagnostic challenge between dementia and the neurocognitive decline associated with BD, particularly in the case of a late-onset BD. Although the available evidence is limited, current evidence demonstrates that BD can indeed be seen as a risk factor for dementia. Therefore, cognitive impairment in individuals with BD should not be overlooked.Disclosure of InterestNone Declared

Demographics, Symptoms, Psychotropic Use, and Caregiver Distress in Patients With Early vs Late Onset Dementia

BackgroundUnderstanding experiences and challenges faced by persons living with Early-Onset Dementia (EOD) compared to individuals diagnosed with Late-Onset Dementia (LOD) is important for the development of targeted interventions. ObjectiveDescribe differences in sociodemographic, neuropsychiatric behavioral symptoms, caregiver characteristics, and psychotropic use. Design, Setting, ParticipantsCross-sectional, retrospective study including 908 UCLA Alzheimer's Dementia Care Program participants (177 with EOD and 731 with LOD). MeasurementsOnset of dementia was determined using age at program enrollment, with EOD defined as age <65 years and LOD defined as age >80 years. Sociodemographic and clinical characteristics were measured once at enrollment. Behavioral symptoms were measured using the Neuropsychiatric Inventory Questionnaire (NPI-Q) severity score and caregiver distress was measured using the NPI-Q distress score. Medications included antipsychotic, antidepressant, benzodiazepines and other hypnotics, antiepileptics, and dementia medications. ResultsEOD compared to LOD participants were more likely men, college graduates, married, live alone, and have fewer comorbidities. EOD caregivers were more often spouses (56% vs 26%, p <0.01), whereas LOD caregivers were more often children (57% vs 10%, p <0.01). EOD was associated with lower odds of being above the median (worse) NPI-Q severity (adjusted odds ratio [aOR], 0.58; 95% CI 0.35–0.96) and NPI-Q distress scores (aOR, 0.53; 95% CI 0.31–0.88). Psychotropic use did not differ between groups though symptoms were greater for LOD compared to EOD. ConclusionPersons with EOD compared to LOD had sociodemographic differences, less health conditions, and fewer neuropsychiatric symptoms. Future policies could prioritize counseling for EOD patients and families, along with programs to support spousal caregivers of persons with EOD.

Abstract MP19: Patterns of Early-Onset and Late-Onset Dementia Incidence in the Dementia Risk Pooling Project

Introduction: Early-onset dementia (EOD) is defined as dementia diagnosed before age 65. While much is known about late-onset dementia (LOD), research on EOD is scarce. The Dementia Risk Pooling Project (DRPP) harmonized data from nine community-based prospective studies, including under-represented racial/ethnic groups. We hypothesized that EOD incidence rates are higher for men than women, and non-Hispanic (NH) Black participants than other race/ethnicity groups. Methods: We used data from eight DRPP cohorts: Age, Gene/Environment Susceptibility-Reykjavik Study, Whitehall II study, Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Honolulu-Asia Aging Study, Multi-Ethnic Study of Atherosclerosis, Sacramento Area Latino Study on Aging, and six Framingham Heart Study cohorts. Individual data were pooled and rigorously harmonized. Race/ethnicity was categorized as self-reported Hispanic, NH White, NH Black, and NH other/unknown. Crude incidence rates and ratios were calculated per 10,000 person-years with 95% confidence intervals. Results: The analytic sample consisted of 56,607 participants, who experienced 7,504 cases of LOD and 124 cases of EOD over a median follow-up of 19.13 (IQR 10.46 - 31.11) years. EOD and LOD incidence rates per 10,000 person-years were 1.95 (95% CI 1.62 - 2.32) and 123.35 (95% CI 120.49 - 126.26), respectively. Compared to women, men had 1.17 (95% CI 0.82 - 1.66) times the rate of EOD but 0.82 (95% CI 0.79 - 0.86) times the rate of LOD. Similarly, compared to NH Whites, Hispanics and participants of other or unknown race/ethnicity had higher rates of EOD but lower rates of LOD. NH Blacks had a higher rate of both EOD and LOD compared to NH Whites, but the association with EOD was more pronounced. Conclusion: In this multi-cohort study with individual participant data, EOD and LOD incidence rates were different across sex and race/ethnicity groups. Some of these differences may be due to longer life expectancy in women and some race/ethnicity groups.

The experiences and perspectives of older adult mental health professional staff teams when supporting people with young-onset dementia.

Background. The diagnosis of young-onset dementia presents significant challenges both for the person and their families, which often differ from the challenges faced with late-onset dementia. Evidence of the experience of service users and carers tends to reveal a negative appraisal of the care received, citing longer diagnosis times, poor clinician knowledge and lack of age-appropriate care. However, evidence looking into staff experiences of supporting someone with young-onset dementia is relatively scarce. The aim of this study was to explore the experiences and reflections of health and social care staff who support people with young-onset dementia within older adult mental health services, and whether their knowledge of the systems they work in could reveal the existence of barriers or facilitators to young-onset dementia care. Methods. Health and social care professionals working with people and carers with young-onset dementia across England were remotely interviewed between September and December 2021. Data were analysed using inductive thematic analysis. Findings. Sixteen staff members were interviewed. Three themes were constructed with six sub-themes. The first theme related to the perception of greater complexity around young-onset dementia support. The second theme describes staff fears around their ability to effectively support people with young-onset dementia, including the perception that young-onset dementia requires specialist input. The final theme describes systemic and structural inefficiencies which provide additional challenges for staff. Conclusions. Providing effective support for people with young-onset dementia and their families requires adjustments both within the clinician role and mental health services. Staff considered young-onset dementia support to be a specialist intervention and felt the services they work for are suited to generic mental health and dementia provision. Findings are discussed with recommendations relating to developing a standardised model of dementia care for young-onset dementia which recognises and responds to the unique experiences of young-onset dementia.

Mapping brain metabolism, connectivity and neurotransmitters topography in early and late onset dementia with lewy bodies

IntroductionEarly-onset dementia with Lewy bodies (EO-DLB) is associated with rapid cognitive decline and severe neuropsychiatric symptoms at onset. MethodsUsing FDG-PET imaging for 62 patients (21 EO-DLB, 41 LO (late-onset)-DLB), we explored brain hypometabolism, and metabolic connectivity in the whole-brain network and resting-state networks (RSNs). We also evaluated the spatial association between brain hypometabolism and neurotransmitter pathways topography. ResultsDirect comparisons between the two clinical subgroups showed that EO-DLB was characterized by a lower metabolism in posterior cingulate/precuneus and occipital cortex. Metabolic connectivity analysis revealed significant alterations in posterior regions in both EO-DLB and LO-DLB. The EO-DLB, however, showed more severe loss of connectivity between occipital and parietal nodes and hyperconnectivity between frontal and cerebellar nodes. Spatial topography association analysis indicated significant correlations between neurotransmitter maps (i.e. acetylcholine, GABA, serotonin, dopamine) and brain hypometabolism in both EO and LO-DLB, with significantly higher metabolic correlation in the presynaptic serotonergic system for EO-DLB, supporting its major dysfunction. ConclusionsOur study revealed greater brain hypometabolism and loss of connectivity in posterior brain region in EO- than LO-DLB. Serotonergic mapping emerges as a relevant factor for further investigation addressing clinical differences between DLB subtypes.