Early-onset Dementia Research Articles

A meta-ethnography of identity formation among people with early-onset dementia

Introduction: Living with dementia can be challenging, even more so for people diagnosed before age 65. Loss of identity is one of the main subjective consequences dementia poses at this stage in life due to the loss of social relations and daily activities. While a growing body of research is reporting the experienced impact of early-onset dementia on identity for this group, studies synthesizing this knowledge are very limited. Therefore, we have conducted a meta-ethnographic review to explain how people with early-onset dementia form their sense of identity. Method: A systematic review of literature from five databases was conducted. Ten original studies published between 2004 and 2020 were included and analyzed using an interpretive approach. Findings: A conceptual interpretation emerged from the analysis, showing that social arenas and activities of daily life, as well as assumptions about dementia and natural aging made by the participants and society, influenced the participants’ sense of identity. Conclusion: Being in nonjudgmental environments can support people with early-onset dementia in creating continuity and positive connections in their personal history. Providing such environments can be a viable venue for healthcare professionals to support people with early-onset dementia in maintaining a positive sense of identity.

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.

Unraveling the mechanistic interplay of mediators orchestrating the neuroprotective potential of harmine.

Neurodegenerative diseases (NDDs) encompass a range of conditions characterized by the specific dysfunction and continual decline of neurons, glial cells, and neural networks within the brain and spinal cord. The majority of NDDs exhibit similar underlying causes, including oxidative stress, neuroinflammation, and malfunctioning of mitochondria. Elevated levels of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), alongside decreased expression of brain-derived neurotrophic factor (BDNF) and glutamate transporter subtype 1 (GLT-1), constitute significant factors contributing to the pathogenesis of NDDs. Additionally, the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) gene has emerged as a significant target for the treatment of NDDs at the preclinical level. It significantly contributes to developmental brain defects, early onset neurodegeneration, neuronal loss, and dementia in Down syndrome. Moreover, an impaired ubiquitin-proteosome system (UPS) also plays a pathological role in NDDs. Malfunctioning of UPS leads to abnormal protein buildup or aggregation of α-synuclein. α-Synuclein is a highly soluble unfolded protein that accumulates in Lewy bodies and Lewy neurites in Parkinson's disease and other synucleinopathies. Recent research highlights the promising potential of natural products in combating NDDs relative to conventional therapies. Alkaloids have emerged as promising candidates in the fight against NDDs. Harmine is a tricyclic β-carboline alkaloid (harmala alkaloid) with one indole nucleus and a six-membered pyrrole ring. It is extracted from Banisteria caapi and Peganum harmala L. and exhibits diverse pharmacological properties, encompassing neuroprotective, antioxidant, anti-inflammatory, antidepressant, etc. Harmine has been reported to mediate its neuroprotective via reducing the level of inflammatory mediators, NADPH oxidase, AChE, BChE and reactive oxygen species (ROS). Whereas, it has been observed to increase the levels of BDNF, GLT-1 and anti-oxidant enzymes, along with protein kinase-A (PKA)-mediated UPS activation. This review aims to discuss the mechanistic interplay of various mediators involved in the neuroprotective effect of harmine.

Genome-Wide DNA Methylation in Early-Onset-Dementia Patients Brain Tissue and Lymphoblastoid Cell Lines.

Epigenetics, a potential underlying pathogenic mechanism of neurodegenerative diseases, has been in the scope of several studies performed so far. However, there is a gap in regard to analyzing different forms of early-onset dementia and the use of Lymphoblastoid cell lines (LCLs). We performed a genome-wide DNA methylation analysis on sixty-four samples (from the prefrontal cortex and LCLs) including those taken from patients with early-onset forms of Alzheimer's disease (AD) and frontotemporal dementia (FTD) and healthy controls. A beta regression model and adjusted p-values were used to obtain differentially methylated positions (DMPs) via pairwise comparisons. A correlation analysis of DMP levels with Clariom D array gene expression data from the same cohort was also performed. The results showed hypermethylation as the most frequent finding in both tissues studied in the patient groups. Biological significance analysis revealed common pathways altered in AD and FTD patients, affecting neuron development, metabolism, signal transduction, and immune system pathways. These alterations were also found in LCL samples, suggesting the epigenetic changes might not be limited to the central nervous system. In the brain, CpG methylation presented an inverse correlation with gene expression, while in LCLs, we observed mainly a positive correlation. This study enhances our understanding of the biological pathways that are associated with neurodegeneration, describes differential methylation patterns, and suggests LCLs are a potential cell model for studying neurodegenerative diseases in earlier clinical phases than brain tissue.

Preoperative Counseling and Surgical Practice: Gynecologic Surgeons' Approach to Ovary-Sparing Hysterectomy [ID 2683432

INTRODUCTION: Since the early 20th century, surgical practices on prophylactic oophorectomy at the time of hysterectomy have fluctuated. This study aims to assess how current gynecologic surgeons are counseling patients on ovary-sparing benign hysterectomies and assess any gaps in provider knowledge. METHODS: Institutional review board exception was obtained. A survey was piloted and underwent several rounds of editing before being sent to members of American Association of Gynecologic Laparoscopists (AAGL) in April 2023. The questionnaire evaluated preoperative counseling on risks and benefits of ovary-sparing hysterectomy for benign indications and surgical practices for when to perform bilateral salpingectomy and oophorectomy. Descriptive statistics and regression analyses were performed. RESULTS: The survey was sent out by email to 6,622 AAGL members, 3,576 opened the email, and 520 completed surveys (14% response rate). Approximately one-half (58%) completed subspeciality training. Most counsel patients on the benefits of ovarian conservation including the prevention of osteoporosis (88%), early onset menopause (87%), cardiovascular disease (84%), and dementia (52%). Fifty percent recommend routine bilateral salpingo-oophorectomy at time of hysterectomy starting at age 61, whereas 38% recommend this be performed at age 51–55 years. CONCLUSION: Gynecologic surgeons are counseling patients on the risks and benefits of ovarian conservation. How frequently ovary-sparing hysterectomies are offered and the age at which bilateral salpingo-oophorectomy is recommended vary by provider. Additional high-quality studies are needed to further understand the optimal timing of oophorectomy at time of benign hysterectomy, and there is also a need for provider education to minimize discrepancy in practice patterns.

A Comprehensive Review and Androgen Deprivation Therapy and Its Impact on Alzheimer's Disease Risk in Older Men with Prostate Cancer.

Prostate cancer (PCa) is one of the most prevalent malignancies affecting males worldwide. Despite reductions in mortality rates due to advances in early identification and treatment methods, PCa remains a major health concern. Recent research has shed light on a possible link between PCa and Alzheimer's disease (AD), which is a significant neurological ailment that affects older males all over the world. Androgen deprivation therapy (ADT), a cornerstone therapeutic method used in conjunction with radiation and palliative care in advanced metastatic PCa cases, is critical for disease management. Evidence reveals a relationship between ADT and cognitive impairment. Hormonal manipulation may cause long-term cognitive problems through processes such as amyloid beta (Aβ) aggregation and neurofibrillary tangles (NFTs). Fluctuations in basal androgen levels can upset the delicate balance of genes that are sensitive to androgen levels, contributing to cognitive impairment. This detailed review dives into the various aspects of PCa aetiology and its relationship with cognitive decline. It investigates the discovery of particular biomarkers, as well as microRNAs (miRNAs), which play important roles in pathogenic progression. The review attempts to identify potential biomarkers associated with ADT-induced cerebral changes, including Aβ oligomer buildup, NFT formation, and tauopathy, which can contribute to early-onset dementia and cognitive impairment. Besides it further aims to provide insights into innovative diagnostic and therapeutic avenues for alleviating PCa and ADT-related cognitive sequelae by unravelling these complicated pathways and molecular mechanisms.

Delusions of love and passion in the behavioral variant of frontotemporal dementia

ABSTRACT sErotomania (de Clérambault’s syndrome) refers to the delusional belief that another person, usually socially unreachable, is in love with the holder of the delusion. The occurrence of erotomania in Frontotemporal Dementia has rarely been reported. We present the unique case of a 59-year-old woman with a strong family history of early-onset dementia in whom erotomania was the initial manifestation that led to a diagnosis of definite Behavioral Variant of Frontotemporal Dementia with a pathogenic missense mutation in the MAPT gene. Based on this case, we propose a hypothetical model for developing erotomania in patients with FTD.

Association of midlife body-weight variability and cycles with earlier dementia onset: a nationwide cohort study

BackgroundGiven the rising awareness of health-related lifestyle modifications, the impact of changes in body weight (BW) on cognitive function and dementia generates significant concern. This study aimed to investigate the association between BW changes and dementia in a middle-aged Korean population.MethodsA retrospective, population-based longitudinal study was conducted utilizing data from the National Health Insurance Service (NHIS) database. Participants aged 40 years or older in 2011 who underwent at least five health checkups between 2002 and 2011 were followed-up for dementia until 2020. A total of 3,635,988 dementia-free Korean aged < 65 at baseline were examined. We analyzed the association between BW variability independent of the mean (VIM) with BW cycle, defined as either an upward or a downward direction of BW, and the risk of incident dementia.ResultsThe results showed an increased risk of dementia in the highest quartile of VIM quartile (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.47–1.58) compared to the lowest quartile of VIM. Additionally, the results showed an even higher increased risk of dementia in the highest BW cycle (≥ 2 cycles of 10% BW = HR 2.00, 95% CI 1.74–1.29). Notably, the combined concept of VIM with BW cycle showed an even higher dementia risk (highest quartile of VIM with ≥ 2 cycles of 10% BW = HR 2.37, 95% CI 2.05–2.74) compared to the baseline group (lowest quartile of VIM with < 3% BW cycle).ConclusionsThe present study highlights the importance of considering BW changes with BW variability along with the BW cycle to assess dementia risk in detail, providing valuable insights for preventive strategies.

A study protocol for identifying aging trajectories toward chronic neurodegenerative diseases by means of Marche regional administrative databases - TREND project.

People are living longer but an increasing number of older people experience chronicity and disability in the latest years of their life. The Marche region is one of the Italian regions where people live the longest lives; therefore, the number of people with age-related chronic diseases is expected to be at least similar, if not higher, compared to the rest of Italy. The identification of the aging trajectories is of huge interest in the arena of public health. Administrative healthcare databases represent valuable reservoirs for reconstructing the trajectories of aging. Here, we present the protocol for a study (TREND project) aimed to integrate existing administrative databases into a Marche regional dataset in order to estimate the prevalence and incidence rates of age-related neurodegenerative diseases (ND), with a specific focus on Parkinsonism and Dementia. The TREND Project is a retrospective cross-sectional study. The source population includes permanent residents in the Marche region aged 40 years and older. A minimal dataset has been built up linking data on drug prescriptions, outpatient services, and diagnosis for hospital admission, from 2014 to 2021 in the Marche Region. Data on clinical outcomes (re-hospitalization, mortality, comorbidities), and therapeutic approaches (drugs and medicines) have been integrated with state-of-the-art statistical methods to define patients into different risk clusters and to analyze the aging trend by assessing the Comorbidity Index (CI) as a proxy for chronicity. Our research contributes to the integration of existing administrative databases on ND to create a Marche regional ND database, support regional health policy, and better understand patients' needs and their aging trajectories. This approach could be implemented also at the National level. Moreover, by linking different administrative data sources, this study sheds light on important issues related to ND, such as early-onset dementia; ethical aspects such as anticipated wills; problems of dementia in patients still in the job market, etc. The results of this study will contribute to the successful implementation of integrated care for patients affected by ND at regional or national levels.

Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons

Frontotemporal dementia (FTD) is an incurable group of early-onset dementias that can be caused by the deposition of hyperphosphorylated tau in patient brains. However, the mechanisms leading to neurodegeneration remain largely unknown. Here, we combined single-cell analyses of FTD patient brains with a stem cell culture and transplantation model of FTD. We identified disease phenotypes in FTD neurons carrying the MAPT-N279K mutation, which were related to oxidative stress, oxidative phosphorylation, and neuroinflammation with an upregulation of the inflammation-associated protein osteopontin (OPN). Human FTD neurons survived less and elicited an increased microglial response after transplantation into the mouse forebrain, which we further characterized by single nucleus RNA sequencing of microdissected grafts. Notably, downregulation of OPN in engrafted FTD neurons resulted in improved engraftment and reduced microglial infiltration, indicating an immune-modulatory role of OPN in patient neurons, which may represent a potential therapeutic target in FTD.

Early-onset dementia and risk of hip fracture and major osteoporotic fractures.

There is limited knowledge about early-onset dementia (EOD) on fracture risk. Individuals ages 50 to 64 were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (2012 to 2019). The association between EOD and fractures and the association between cholinesterase inhibitors for EOD and fractures were evaluated using logistic regression analyses. We identified 13,614 EOD patients and 9,144,560 cognitively healthy individuals. The analysis revealed that EOD was associated with an increased risk of hip fractures (adjusted odds ratio, 95% confidence interval: 8.79, 7.37-10.48), vertebral fractures (1.73, 1.48-2.01), and major osteoporotic fractures (2.05, 1.83-2.30) over 3 years. The use of cholinesterase inhibitors was significantly associated with a reduction in hip fractures among EOD patients (0.28, 0.11-0.69). EOD patients have a higher risk of osteoporotic fractures than cognitively healthy individuals. The use of cholinesterase inhibitors may reduce the risk of hip fracture among EOD patients. It is unknown whether early-onset dementia (EOD) increases the risk of fractures. We identified 13,614 individuals with EOD using a nationwide administrative database. Patients with EOD have a higher risk of hip, vertebral, and major osteoporotic fractures. The use of cholinesterase inhibitors may reduce hip fracture among patients with EOD.

Exploring museums and libraries as new sites for Cognitive Stimulation Therapy

What role can museums and libraries play in improving people's health and wellbeing? This is the question staff at the V&amp;A Museum are exploring through Cognitive Stimulation Therapy (CST), a treatment designed for adults with early onset dementia, traditionally delivered in a clinical setting. Guided by experts from the dementia charity Resonate Arts and the NHS's Memory Service, V&amp;A curators and librarians are discovering the great potential of the museum and its collections to improve and enrich lives.

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

The Role of Alcohol Use Disorders in the Development and Progression of Dementia

IntroductionIn recent years, there has been an increase in interest and research into the link between alcohol use disorders (AUD) and dementia. Alcohol use disorders, which are characterised by excessive and problematic alcohol consumption, have been associated to a variety of detrimental health effects, including liver disease, cardiovascular difficulties, and cognitive impairments.ObjectivesTo explore the link between alcohol use disorders and dementia onset and progression, explaining probable causes and emphasising preventive approaches.Methods The present study involved a thorough examination of relevant research papers, with a specific emphasis on longitudinal cohort studies, neuropathological observations, and biochemical interactions pertaining to the effects of alcohol on the brain. In addition to the aforementioned criteria, the review also took into account other complicating factors, including choices regarding lifestyle, genetic predisposition, and coexisting medical conditions.Results The results indicate a strong association between prolonged and excessive alcohol consumption and a heightened susceptibility to the early onset of dementia. The mechanisms underlying alcohol-related neurological damage encompass direct neurotoxic effects of alcohol, thiamine shortage, and alcohol-related cerebrovascular illness. Moreover, it is worth noting that alcohol use disorder (AUD) has the potential to worsen the advancement of neurodegenerative processes in individuals already diagnosed with dementia.ConclusionsThe association between AUD (Alcohol Use Disorder) and dementia is complex and involves multiple factors, presenting considerable difficulties in terms of clinical intervention and treatment. The use of early intervention strategies and public health initiatives focused on addressing alcohol use disorder (AUD) could have a significant impact on preventing or reducing the development of dementia.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.

조기발병 치매환자의 사회참여 활성화를 위한 캘리그래피 중심 집단미술치료 사례연구

Objectives The purpose of this study was to analyze how group art therapy using calligraphy impacts the social engagement activation of early onset dementia patients.&#x0D; Methods The group therapy was conducted for six early-onset dementia patients who were registered at the S Metropolitan Center for Dementia. The program consisted of eleven sessions and ran once a week from July 31, 2023, to November 6, 2023. The group art therapy program involved education and learning in each session to enable early-onset dementia patients to use the medium themselves and complete artworks. Based on this, participants were guided to complete artistic works. The research data were collected and analyzed using pre- and post-data (CIST and SGDS-K), therapist's session evaluations, observation notes, pre- and post-DAS (The Draw-a-Story) drawing test, and in-depth interviews with 2 participants and partners of 3 participants. The results of the in-depth interviews were cross-analyzed and categorized by two researchers under supervision to derive the findings.&#x0D; Results As a result, firstly, most of the patients who participated in the program maintained or developed their cognitive skills and lowered their depression inventory. Second, participants indicated improvement in their social skills and an increase in awareness and experience related to social engagement. Based on the experience of the art therapy group, participants’ showed positive changes in awareness of social engagement&#x0D; Conclusions This study is meaningful in confirming the impact of group art therapy using calligraphy on alleviating difficulties and promoting social engagement in early-onset dementia patients. Therefore, it is expected to contribute to the activation of social engagement for early-onset dementia patients.&#x0D;

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.

Neuropsychological Profiles, Etiologies, and Medical Comorbidities in Early-Onset Dementia and Cognitive Impairment: A Memory Outpatient Clinic Cohort Study.

Although early-onset dementia (EOD) is associated with diagnostic challenges that differ from those of related to late-onset dementia, only limited studies have addressed the neuropsychological and health characteristics or specified the diagnoses underlying early-onset cognitive impairment in a real-world clinical setting. To investigate the neuropsychological profiles, etiologies, and comorbidities of an unselected cohort of memory clinic patients (≤65 years at symptom onset). The patients' (n = 210) diagnoses were determined based on comprehensive diagnostic workup. Medical comorbidities and neuropsychological profiles were compared between clinically relevant patient groups, namely early-onset dementia (n = 55), mild cognitive impairment due to vascular or suspected neurodegenerative (MCI-n, n = 35) or non-neurodegenerative (MCI-o, n = 106) etiologies, and subjective cognitive decline (n = 14). The most prevalent diagnoses were Alzheimer's disease (AD, 14%) and depression (11%). Multiple prior medical conditions were common (67%); however, EOD patients had fewer other diagnoses (p = 0.008) than MCI-o patients. Compared to other groups, EOD patients had more severe deficits (p < 0.001) on immediate and delayed memory, processing speed, symptom awareness, and global cognition. AD patients had weaker memory retention ability but less behavioral symptoms than frontotemporal dementia (FTD) patients (p≤0.05). Depression was associated with better immediate memory, symptom awareness, and global cognition than AD and FTD (p < 0.05). EOD is associated with more severe and widespread neuropsychological deficits but fewer prior medical diagnoses than nondegenerative etiologies of cognitive impairment. AD and depression are common etiologies and the neuropsychological profiles are partly overlapping; however, memory, symptom awareness and global cognitive impairment measures may help in the differential diagnosis.

Prevalence and trend of central nervous system–active medication polypharmacy among US commercially insured adults with vs without early-onset dementia: a multi-year cross-sectional study

BackgroundLimited data exist on the prevalence and trend of central nervous system (CNS)-active medication polypharmacy among adults with early-onset dementia (EOD) and whether these estimates differ for adults without EOD but with chronic pain, depression, or epilepsy, conditions managed by CNS-active medications.MethodsA multi-year, cross-sectional study using 2012–2021 MarketScan Commercial Claims data was conducted among adults aged 30 to 64 years with EOD and those without EOD but having a diagnosis of chronic pain, depression, or epilepsy as comparison groups. For each disease cohort, the primary outcome was CNS-active medication polypharmacy defined as concurrent use of ≥ 3 CNS-active medications on the US Beers Criteria list that overlapped for > 30 consecutive days during 12 months following a randomly selected medical encounter with the disease diagnosis. A separate multivariate modified Poisson regression model was used to estimate time trends in CNS polypharmacy in each disease cohort. Differences in trend estimates between EOD and non-EOD disease cohorts were examined by an interaction between EOD status and yearly time.ResultsFrom 2013 to 2020, the annual crude prevalence of CNS polypharmacy was higher among adults with EOD (21.2%–25.0%) than adults with chronic pain (5.1%–5.9%), depression (14.8%–21.7%), or epilepsy (20.0%–22.3%). The adjusted annual prevalence of CNS polypharmacy among patients with EOD did not significantly change between 2013 and 2020 (adjusted prevalence rate ratio [aPRR], 0.94; 95% CI, 0.88–1.01), whereas a significant decreasing trend was observed among non-EOD cohorts with chronic pain (aPRR, 0.66; 95% CI, 0.63–0.69), depression (aPRR, 0.81; 95% CI, 0.77–0.85), and epilepsy (aPRR, 0.86; 95% CI, 0.83–0.89). The interaction analysis indicated that patients with epilepsy and depression (vs with EOD) had a decreasing probability of CNS-active medication polypharmacy over time (aPRR, 0.98 [95% CI, 0.98–0.99]; P < .001 for interaction for both conditions).ConclusionsThe prevalence of CNS polypharmacy among US commercially insured adults with EOD (vs without) was higher and remained unchanged from 2013 to 2021. Medication reviews of adults with EOD and CNS polypharmacy are needed to ensure that benefits outweigh risks associated with combined use of these treatments.