Early-onset Dementia Patients Research Articles

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.

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.

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;

조기발병 치매환자의 역할유지를 위한 지역사회 기반 활동프로그램 사례연구

This study aimed to understand the effects of a community-based activity program on instrumental activities of daily living (IADL), cognitive function, and depressive mood in patients with early onset dementia (EOD), and to provide basic data for community-based activity programs to maintain the role of patients with EOD. One patient with EOD who visited the Center for Dementia in S city, Seoul, from August to November 2021 was enrolled in the program. This was conducted for 120 min once a week for 8 weeks. The activity program was implemented based on the Model of Human Occupation (MOHO), focusing on solving problems recognized by patients and caregivers. Compared with before and after the implementation of the activity program, the IADL and cognitive function of patients with dementia improved, and depressive mood decreased. As EOD rapidly progresses, active intervention in the early stages is necessary to delay symptoms and prevent the deterioration of activities of daily living (ADL) and social activity performance skills. Therefore, establishing a systematic treatment and system that can promote participation in community activities so that EOD patients living in the community can maintain their social role as well as interventions to delay the deterioration of symptoms is necessary, and institutional support should be provided.

Characteristics of Early Onset Dementia and Caring Experiences and Service Needs of Family Caregivers: A Mixed Methods Study

Purpose: The purpose of this mixed methods study was to explore the caring experiences of the family caregivers of patients with early-onset dementia, and identify the characteristics of early-onset dementia.Methods: A qualitative study was conducted using Colaizzi‘s phenomenological method to explore the caring experiences and service needs of ten family caregivers. A quantitative study was carried out by secondary data analysis to compare the differences in disease characteristics and comorbidities between early and late-onset dementia.Results: The experiences of the family caregivers of patients with early-onset dementia were ‘Learning about dementia’, ‘Away from everyday life’, ‘Facing dementia’, and ‘Barely managing’. The study also revealed that one out of five dementia patients had early-onset dementia. However, most dementia services are concentrated on late-onset dementia. Thus, the family and caregivers of early-onset dementia patients experience relatively inadequate services.Conclusion: This study’s findings identified the characteristics of early-onset dementia, as well as the caring experiences and service needs of family caregivers from a more holistic perspective, and will contribute to the development of adequate nursing intervention programs and policies in the future.

Comprehensive genetic screening of early-onset dementia patients in an Austrian cohort-suggesting new disease-contributing genes

Early-onset dementia (EOD), with symptom onset before age 65, has a strong genetic burden. Due to genetic and clinical overlaps between different types of dementia, whole-exome sequencing (WES) has emerged as an appropriate screening method for diagnostic testing and novel gene-finding approaches. We performed WES and C9orf72 repeat testing in 60 well-defined Austrian EOD patients. Seven patients (12%) carried likely disease-causing variants in monogenic genes, PSEN1, MAPT, APP, and GRN. Five patients (8%) were APOE4 homozygote carriers. Definite and possible risk variants were detected in the genes TREM2, SORL1, ABCA7 and TBK1. In an explorative approach, we cross-checked rare gene variants in our cohort with a curated neurodegeneration candidate gene list and identified DCTN1, MAPK8IP3, LRRK2, VPS13C and BACE1 as promising candidate genes. Conclusively, 12 cases (20%) carried variants relevant to patient counseling, comparable to previously reported studies, and can thus be considered genetically resolved. Reduced penetrance, oligogenic inheritance and not yet identified high-risk genes might explain the high number of unresolved cases. To address this issue, we provide complete genetic and phenotypic information (uploaded to the European Genome-phenome Archive), enabling other researchers to cross-check variants. Thereby, we hope to increase the chance of independently finding the same gene/variant-hit in other well-defined EOD patient cohorts, thus confirming new genetic risk variants or variant combinations.

Tau and amyloid PET imaging with 18F‐PI‐2620 and 18F‐Florbetaben in patients with early‐onset dementia and healthy controls

AbstractBackgroundAbnormal deposits of tau protein and beta‐amyloid are the two fundamental pathological features of Alzheimer's disease (AD). The research framework for AD diagnosis proposes categorizing subjects based on biomarker evidence of pathology using the ATN classification system (amyloid, tau, neurodegeneration). In‐vivo detection of amyloid pathology using positron emission tomography (PET) is well established and new generation tau PET tracers like 18F‐PI‐2620 have shown a high binding affinity for aggregated tau without significant off‐target binding. The purpose of this study is to describe the ability of 18F‐PI‐2620 to detect tau pathology in patients with early‐onset dementia (EOD) with proven amyloid pathology.MethodTen patients with EOD and positive 18F‐Florbetaben amyloid PET (age range 54‐64y, 8 with suspected early‐onset AD (EOAD) and 2 with logopenic variant primary progressive aphasia (lvPPA)), along with 14 healthy controls (HC) (age range 54‐76y) underwent dynamic PET scans for 75 minutes after injection of 18F‐PI‐2620 to examine the presence of tau‐pathology in cortical and deep brain regions. Specific binding ratios were derived from averaged PET images from 45‐75 min post‐injection.ResultIn 9 out of 10 EOD patients, 18F‐PI‐2620 uptake was robust and extensive predominantly in cortical regions with relative sparing of deep brain regions. In the remaining EOD case, binding was low but with the same distribution pattern described for other EOD patients. In one HC, significant, specific uptake was observed predominantly in deep brain regions. 18F‐PI‐2620 administration was safe and well‐tolerated.ConclusionOur preliminary results suggest an excellent performance of the tracer 18F‐PI‐2620 to detect tau deposits in EOAD and lvPPA. Tau PET imaging with 18F‐PI‐2620, in conjunction with 18F‐Florbetaben amyloid PET, distinctly discriminates between early‐onset dementias due to AD pathology from HC. These results also support the usefulness of 18F‐PI‐2620 for visualizing tau aggregation in EOD. Finally, 18F‐Florbetaben and 18F‐PI‐2620 appear to be reliable tools for establishing the ATN biomarker status in EOD patients. Nevertheless, further studies are needed to confirm these preliminary results.

Microvascular Changes in the Retina Correlate with MRI Markers in Patients with Early-Onset Dementia.

Background and Aims: Recent reports suggest that results from imaging retinal microvascular changes with optical coherence tomography angiography (OCTA) in dementia patients reflect cerebral microcirculation changes that occur during dementia. Macula microvascular impairment has been shown in dementia patients compared to controls, but very little is known about its correlation with radiological visual rating scores associated with dementia. We aimed to explore the association between retinal microvasculature and radiological visual rating in early-onset dementia (EOD) patients. Methods: Swept-source OCTA (SS-OCTA) was used to image the retinal microvasculature of all EOD patients. Automated software in the OCTA tool segmented and measured the densities in the superficial vascular plexus (SVC) and deep vascular plexus (DVC) and foveal avascular zone (FAZ) areas. Radiological visual rating scores were evaluated on all MR images. Results: Medial temporal lobe atrophy (MTA) scores significantly correlated with FAZ area (p = 0.031) in EOD patients after adjusting for risk factors. PWMH correlated with SVC (p = 0.032) while DWMH significantly correlated with SVC (p = 0.007), DVC (p = 0.018) and FAZ (p = 0.001) in EOD patients. Discussion: FAZ changes correlated with MTA scores in EOD patients, while retinal microvasculature correlated with white matter hyperintensity. Our report suggests that microvascular changes in the retina may reflect cortical changes in the brain of EOD patients.

NDUFA1 p.Gly32Arg variant in early-onset dementia

Early-onset dementia (EOD) is highly heritable. However, in many EOD cases the genetic etiology remains unknown. Mitochondrial dysfunction is associated with neurodegeneration and the complex I (CI) deficiency is the most common enzyme deficiency in diseases related to oxidative phosphorylation. The X-chromosomal NDUFA1 gene is essential for the activity of CI. Mutations in NDUFA1 are associated with mitochondrial diseases especially with Leigh syndrome. CI deficiency is also associated with neurodegenerative diseases, such as Alzheimer's disease (AD). The aim of this study was to evaluate the role of NDUFA1 variants in EOD patients. Next-generation sequencing panel was used to screen NDUFA1 variants in a cohort of 37 EOD patients with a family history of dementia or an atypical or rapidly progressive course of disease. We identified a hemizygous p.Gly32Arg variant in two brothers with AD. Subsequent screening of the variant in a larger cohort of EOD patients (n = 279) revealed three additional variant carriers (one male and two heterozygote females), suggesting that NDUFA1 variant p.Gly32Arg may play a role in neurodegenerative dementia.

Choriocapillaris Changes Are Correlated With Disease Duration and MoCA Score in Early-Onset Dementia.

Purpose: Imaging of the choroid may detect the microvascular changes associated with early-onset dementia (EOD) and may represent an indicator for detection of the disease. We aimed to analyze the in vivo choriocapillaris (CC) flow density in EOD patients using optical coherence tomography angiography (OCTA) and evaluate the association with its clinical measures.Methods: This cross-sectional study used the OCTA to image and analyze the choriocapillaris (CC) of 25 EOD patients and 20 healthy controls. Choriocapillaris flow density in the 3 mm area and 6 mm area was measured by an inbuilt algorithm in the OCT tool. Brain volume using magnetic resonance imaging and cognitive assessment was done and recorded.Results: Significantly reduced capillary flow density of the choriocapillaris was seen in EOD patients when compared to healthy controls in the 3.0 mm (P = 0.001) and 6.0 mm (P < 0.001) area respectively. Montreal Cognitive Assessment (MoCA) scores in EOD patients positively correlated with choriocapillaris flow density in the 3 mm area (Rho = 0.466, P = 0.021). Disease duration of EOD patients also negatively correlated with choriocapillaris density in the 3 mm area (Rho = −0.497, P = 0.008).Discussion: Our report suggests that choriocapillaris damage may be a potential indicator of early-onset dementia. Microvascular impairment may be involved in the early phase of dementia without aging playing a role in its impairment.Clinical Trial Registration: www.ClinicalTrials.gov, ChiCTR2000041386.

A Concept Map of Psychological Difficulties and Coping Strategies Experienced by Spouses of Early-onset Dementia Patients

A Concept Map of Psychological Difficulties and Coping Strategies Experienced by Spouses of Early-onset Dementia Patients

Performance on the Picture Description Tasks in Patients with Late Dementia of the Alzheimer’s Type

Linguistic problems such as word finding difficulties, writing disorders, problems in phonetic and syntactic use are one of the most important problems seen in individuals with Alzheimer’s Disease (AD). Compared to late onset, early onset dementia patients experience these problems at a faster rate. However; the linguistic abilities of LAD patients are quite similar to the healthy people. In this study, the picture description performance of late onset AD patients and healthy people were compared in terms of affirmative, negative and interrogative sentence structures. According to the results, there is a significant difference within groups. Late onset AD patients produced more declarative and interrogative sentences in picnic picture description test.

Performance on the Picture Description Tasks in Patients with Late Dementia of the Alzheimer’s Type

Linguistic problems such as word finding difficulties, writing disorders, problems in phonetic and syntactic use are one of the most important problems seen in individuals with Alzheimer’s Disease (AD). Compared to late onset, early onset dementia patients experience these problems at a faster rate. However; the linguistic abilities of LAD patients are quite similar to the healthy people. In this study, the picture description performance of late onset AD patients and healthy people were compared in terms of affirmative, negative and interrogative sentence structures. According to the results, there is a significant difference within groups. Late onset AD patients produced more declarative and interrogative sentences in picnic picture description test.

The epidemiology of the different clinical presentations of early onset dementia

AbstractBackgroundIt is known that patients with Early Onset Dementia (EOD), defined as dementia with symptoms onset before the age of 65, frequently present with atypical clinical syndromes. However, the epidemiology of the different presentations of EOD, including the clinical variants of Alzheimer’s dementia (AD) and frontotemporal dementia (FTD), has never been investigated altogether in the same population‐based study, probably because their characterisation is relatively recent, and subsequent to the advent of AD biomarkers. Epidemiologic data on all‐causes of EOD are also scarce, inconsistent, and mostly based on low‐level clinical assessment.MethodWe investigated the epidemiology of EOD in the province of Modena, Northern Italy (700,000 inhabitants), by identifying newly‐diagnosed EOD patients retrospectively from January 2006 to December 2016, and prospectively from January 2017 to June 2019. Diagnosis was based on extended clinical and neuropsychological assessment, and supported by the use of imaging and cerebrospinal fluid biomarkers in the majority of cases.ResultEOD age‐ and sex‐adjusted incidence was 6.45/100000 inhabitants/year during the 2016‐2019 period, corresponding to 46 new cases per year in the overall study population. At census day (30th June 2019), there were 258 patients with a clinical diagnosis of EOD (123 males) in the province of Modena. Crude Prevalence was 74.3/100000 (71.2 in males and 77.4 in females) in the population aged 30‐64, and 119.9/100000 (117.1 in males and 122.6 in females) in the population aged 45‐64. Overall crude prevalence was 36.4/100000 inhabitants (35.5/100000 in males, 37.4/100000 in females). The most frequent EOD was the amnestic variant of AD (crude incidence of 21.6/100000 and prevalence of 5/100000 persons aged 30‐64 years), followed by the behavioural variant of FTD (crude incidence of 14.1/100000 and prevalence of 2.8/100000 persons aged 30‐64 years), and logopenic variant of primary progressive aphasia (crude incidence of 5.8/100000 and prevalence of 0.8/100000 persons aged 30‐64 years).ConclusionWe provide the first report on incidence and prevalence of all the clinical presentations of EOD including different variants of AD and FTD. These epidemiological data will benefit the clinical reasoning of clinicians faced with dementia in young patients and will allow to improve dementia care organisation.

Determinants of caregiver burden in early onset dementia

AbstractBackgroundCaregivers of patients with early onset dementia (EOD) experience high levels of burden, which is known to be affected by financial and social variables, as well as by psychological features of the caregiver and patient’s symptoms. However, it is not known how all these factors reciprocally interact in determining the burden of caregivers of EOD patients. We investigated multiple determinants of burden in a comprehensive model.MethodConsecutive eligible patients with EOD and their caregivers were recruited from the Cognitive Neurology Clinic of the Modena University Hospital, Italy. Patients underwent extended clinical, imaging and neuropsychological assessment. Caregivers were interviewed and asked to fill in questionnaires to gain information on patients’ symptoms, caregiver burden (Zarit Burden Interview), caregiver psychological distress (Relative Stress Scale). Patient/caregiver demographics, social and clinical variables were entered in linear multiple regression models and mediation models to explore if the effect on burden is mediated by stress.ResultData from 89 EOD patient‐caregiver dyads were examined. Caregiver burden was positively related to female caregiver sex (b=0.44,p=0.0002), severity of patient’s behavioral symptoms (b=0.32,p=0.0004), diagnostic delay (b=0.18,p=0.017) and financial distress of the family (b=0.28, p=0.0008). Significant factors reducing the burden were caregiver perception of patient’s quality of life (b=‐0.20, p=0.005), disease duration (b=‐0.27,p=0.0003), caregiver age (b=‐0.31,p=0.0017), offspring number (b=‐0.25,p=0.0004), patient’s education (b=‐0.15,p=0.022), region of birth (b=‐0.17,p=0.025) and number of days off work (b=‐0.15, p&lt;0.0001) (adjusted‐R2=0.64). While the effect of financial distress, number of caregiver’s days off‐work, patient’s disease duration, and caregiver sex was entirely mediated by the level of caregiver stress, the effect of diagnostic delay and of proxies of family or social network on burden was direct.ConclusionMost of the effect of the known determinants of the burden of caregivers is mediated by caregivers’ level of stress, in particular for female caregivers. In particular, the number of days off‐work that the caregiver can take is a variable on which action can be taken to reduce the caregivers’ stress, hence their burden. However, as some determinants are independent from stress, direct actions should be aimed at increasing social networks and shortening diagnostic delay to reduce caregiver burden.

Dietary Habits and Risk of Early-Onset Dementia in an Italian Case-Control Study

Risk of early-onset dementia (EOD) might be modified by environmental factors and lifestyles, including diet. The aim of this study is to evaluate the association between dietary habits and EOD risk. We recruited 54 newly-diagnosed EOD patients in Modena (Northern Italy) and 54 caregivers as controls. We investigated dietary habits through a food frequency questionnaire, assessing both food intake and adherence to dietary patterns, namely the Greek-Mediterranean, the Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. We modeled the relation between dietary factors and risk using the restricted cubic spline regression analysis. Cereal intake showed a U-shaped relation with EOD, with risk increasing above 350 g/day. A high intake (>400 g/day) of dairy products was also associated with excess risk. Although overall fish and seafood consumption showed no association with EOD risk, we found a U-shaped relation with preserved/tinned fish, and an inverse relation with other fish. Similarly, vegetables (especially leafy) showed a strong inverse association above 100 g/day, as did citrus and dry fruits. Overall, sweet consumption was not associated with EOD risk, while dry cake and ice-cream showed a positive relation and chocolate products an inverse one. For beverages, we found no relation with EOD risk apart from a U-shaped relation for coffee consumption. Concerning dietary patterns, EOD risk linearly decreased with the increasing adherence to the MIND pattern. On the other hand, an inverse association for the Greek-Mediterranean and DASH diets emerged only at very high adherence levels. To the best of our knowledge, this is the first study that explores the association between dietary factors and EOD risk, and suggests that adherence to the MIND dietary pattern may decrease such risk.

Environmental Risk Factors for Early-Onset Alzheimer's Dementia and Frontotemporal Dementia: A Case-Control Study in Northern Italy.

Background: Early-onset dementia (EOD) is defined as dementia with symptom onset before 65 years. The role of environmental risk factors in the etiology of EOD is still undefined. We aimed at assessing the role of environmental risk factors in EOD etiology, taking into account its different clinical types. Methods: Using a case-control study, we recruited all EOD cases referred to Modena hospitals from 2016 to 2019, while the referent population was drawn from cases’ caregivers. We investigated residential history, occupational and environmental exposures to chemicals and lifestyle behaviors through a self-administered questionnaire. We computed the odds ratios of EOD risk (overall and restricting to the Alzheimer’s dementia (AD) or frontotemporal dementia (FTD) diagnoses) and the corresponding 95% confidence intervals using an unconditional logistic regression model. Results: Fifty-eight EOD patients (19 FTD and 32 AD) and 54 controls agreed to participate. Most of the investigated exposures, such as occupational exposure to aluminum, pesticides, dyes, paints or thinners, were associated with an increased odds ratio (OR) for FTD but not for AD. Long-term use of selenium-containing dietary supplements was associated with increased OR for EOD and, particularly, for FTD. For both EOD forms, smoking and playing football showed an increased odds ratio, while cycling was associated with increased risk only in FTD. Overall sports practice appeared to be a protective factor for both types. Conclusions: Our results suggest a role of environmental and behavioral risk factors such as some chemical exposures and professional sports in EOD etiology, in particular with reference to FTD. Overall sports practice may be associated with a reduced EOD risk.

Genetic Analysis of Chinese Patients with Early-Onset Dementia Using Next-Generation Sequencing.

ObjectiveEarly-onset dementia (EOD) is a relatively uncommon form of dementia that afflicts people before age 65. Only a few studies analyzing the genetics of EOD have been performed in the Chinese Han population. Diagnosing EOD remains a challenge due to the diverse genetic and clinical heterogeneity of these diseases. The aim of this study was to investigate the genetic spectrum and clinical features of Chinese patients with EOD.Materials and MethodsA total of 49 EOD patients were recruited. Targeted next-generation (NGS) analyses were performed to screen for all of the known genes associated with dementia. Possible pathogenic variants were confirmed by performing Sanger sequencing. The genetic spectrum and clinical features of the EOD patients were analyzed.ResultsSeven previously reported pathogenic variants (p.I213T and p.W165C in PSEN1; p.D678N in APP; c.1349_1352del in TBK1; p.P301L and p.R406W in MAPT; p.R110C in NOTCH3) and two novel variants of uncertain significance (p.P436L in PSEN2; c.239-11G>A in TARDBP) were identified.ConclusionOur study demonstrated the genetic spectrum and clinical features of EOD patients, and it reveals that genetic testing of known causal genes in EOD patients can help to make a precise diagnosis.

Does health-related quality of life in Asian informal caregivers differ between early-onset dementia and late-onset dementia?

Early-onset dementia (EOD) (defined as dementia onset before age 65) presents specific challenges and issues, adding to the negative impact of dementia on the health-related quality of life (HRQOL) of both patients and their caregivers. However, very few published studies have specifically compared the HRQOL of caregivers of people with EOD and late-onset dementia (LOD). This information is critical in allocating and prioritizing scarce health-care resources. We aimed to assess the HRQOL of primary informal caregivers of community-dwelling individuals with EOD in Singapore and compare it with that of caregivers of individuals with LOD. This was a cross-sectional study of consecutive patient-caregiver dyads from a tertiary dementia clinic. No significant differences in disease severity were found between the 111 EOD and 235 LOD patient-caregiver dyads. The mean Mental Component Summary score of the 36-item Short-Form Health Survey version 2 was significantly worse in caregivers of EOD patients than in LOD caregivers (mean: 41.42 vs 45.12, P = 0.001), although the mean Physical Component Summary scores were comparable (49.71 vs 49.53, P = 0.934). However, the impact of dementia early onset on caregivers' mental health diminished immediately after adjustment for the disease severity indicators, of which the Neuropsychiatric Inventory Questionnaire distress score was the only significant clinical factor (regression coefficient β = -0.29, P < 0.001). The amount of variability in the HRQOL of the caregivers explained by patient and caregiver factors across all the models was rather small (adjusted R2 = 19.3% for the Mental Composite Score, 5.2% for Physical Composite Score). Caregivers of EOD patients had worse mental health than LOD caregivers probably because individual with EOD have more behavioural disturbances. This reinforces the indispensable role of managing behavioural problems when caring for a family member with dementia, especially for EOD. HRQOL ideally needs to be assessed based on self-report rather than inferences from indirect data such as the subjective caregiver burden.

Mutation Analysis of the Genes Associated with Parkinson's Disease in a Finnish Cohort of Early-Onset Dementia.

Alzheimer's disease, frontotemporal lobar degeneration, dementia with Lewy bodies, and Parkinson's disease (PD) overlap in clinical characteristics, neuropathology, and genetics. The aim of this study was to evaluate the role of pathogenic mutations and rare variants in genes associated with PD among early-onset dementia (EOD) patients. Rare non-synonymous variants (MAF < 0.01) in ten genes (SNCA, PARK2, PARK7, LRRK2, PINK1, ATP13A2, UCHL1, HTRA2, GBA, and SNCAIP) and low-frequency (MAF < 0.05) GBA variants were screened using a targeted next-generation sequencing panel in a strictly defined cohort of 37 early-onset (age at onset (AAO) <65 years) dementia patients presenting with atypical features (e.g., myoclonia or spasticity), rapidly progressive course of the disease or with a family history of dementia. The identified variations were further screened in a larger cohort of EOD (n = 279, mean AAO 57, range 36-65) patients. No pathogenic mutations were found, but we identified seven possible risk variants for neurodegeneration (LRRK2 p.Arg793Met, PARK2 p.Ala82Glu, SNCAIP p.Arg240Gln, SNCAIP p.Phe369Leu, GBA p.Asn409Ser, GBA p.Glu365Lys, GBA p.Thr408Met). Altogether, the frequency of these variants was two times higher in the first selected cohort compared to the whole cohort. This suggests that specific rare variants in the genes associated with PD might play a role also especially in familial EOD.