Global incidence of young-onset dementia: A systematic review and meta-analysis.

INTRODUCTION: Reliable data on the incidence rates for young-onset dementia (YOD) are lacking, but are necessary for research on disease etiology and to raise awareness among health care professionals. METHODS: We performed a systematic review and meta-analysis on population-based studies on the incidence of YOD, published between January 1, 1990 and February 1, 2022, according to Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines. Data were analyzed using random-effects meta-analyses. Results were age-standardized, and heterogeneity was assessed by subgroup analyses and meta-regression. RESULTS: Sixty-one articles were included. Global age-standardized incidence rates increased from 0.17/100,000 in age 30 to 34 years, to 5.14/100,000 in age 60 to 64 years, giving a global total age-standardized incidence rate of 11 per 100,000 in age 30 to 64. This corresponds to 370,000 new YOD cases annually worldwide. Heterogeneity was high and meta-regression showed geographic location significantly influenced this heterogeneity. DISCUSSION: This meta-analysis shows the current best estimate of YOD incidence. New prospective cohort studies are needed.

Risk Factors for Young-Onset Dementia in the UK Biobank.

Importance: There is limited information on modifiable risk factors for young-onset dementia (YOD). Objective: To examine factors that are associated with the incidence of YOD. Design, Setting, and Participants: This prospective cohort study used data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until March 31, 2021, for England and Scotland, and February 28, 2018, for Wales. Participants younger than 65 years and without a dementia diagnosis at baseline assessment were included in this study. Participants who were 65 years and older and those with dementia at baseline were excluded. Data were analyzed from May 2022 to April 2023. Exposures: A total of 39 potential risk factors were identified from systematic reviews of late-onset dementia and YOD risk factors and grouped into domains of sociodemographic factors (education, socioeconomic status, and sex), genetic factors (apolipoprotein E), lifestyle factors (physical activity, alcohol use, alcohol use disorder, smoking, diet, cognitive activity, social isolation, and marriage), environmental factors (nitrogen oxide, particulate matter, pesticide, and diesel), blood marker factors (vitamin D, C-reactive protein, estimated glomerular filtration rate function, and albumin), cardiometabolic factors (stroke, hypertension, diabetes, hypoglycemia, heart disease, atrial fibrillation, and aspirin use), psychiatric factors (depression, anxiety, benzodiazepine use, delirium, and sleep problems), and other factors (traumatic brain injury, rheumatoid arthritis, thyroid dysfunction, hearing impairment, and handgrip strength). Main Outcome and Measures: Multivariable Cox proportional hazards regression was used to study the association between the risk factors and incidence of YOD. Factors were tested stepwise first within domains and then across domains. Results: Of 356 052 included participants, 197 036 (55.3%) were women, and the mean (SD) age at baseline was 54.6 (7.0) years. During 2 891 409 person-years of follow-up, 485 incident YOD cases (251 of 485 men [51.8%]) were observed, yielding an incidence rate of 16.8 per 100 000 person-years (95% CI, 15.4-18.3). In the final model, 15 factors were significantly associated with a higher YOD risk, namely lower formal education, lower socioeconomic status, carrying 2 apolipoprotein ε4 allele, no alcohol use, alcohol use disorder, social isolation, vitamin D deficiency, high C-reactive protein levels, lower handgrip strength, hearing impairment, orthostatic hypotension, stroke, diabetes, heart disease, and depression. Conclusions and Relevance: In this study, several factors, mostly modifiable, were associated with a higher risk of YOD. These modifiable risk factors should be incorporated in future dementia prevention initiatives and raise new therapeutic possibilities for YOD.

Diagnosis and Care Use for People with Young-Onset Dementia in Primary Care in the Netherlands.

BACKGROUND: Timely diagnosis and adequate care is important for persons with young-onset dementia (YOD) and their caregivers, due to the high impact of the disease. Initiating care can be difficult for the general practitioner (GP) and other healthcare professionals. OBJECTIVE: Provide insight in the care use of persons with YOD and identify factors influencing care use. METHODS: A primary care register was used for this study. Information on the care use of persons with YOD was extracted from the GPs written notes. Information entailed time until start of care use, reasons and factors influencing the GP's decision, and reasons and factors influencing actual care use were included. Analyses included quantitative explorative descriptive analyses, and qualitative manifest content analyses. RESULTS: 75 persons with YOD were included in this study. The main reason for GPs to refer for diagnosis was concerns of caregivers. After diagnosis, 72% of the persons were assigned a case manager, 42.7% received day care, and 44% were admitted to a long-term care facility. A higher percentage of persons without a case manager was admitted to a long-term care facility (64%) compared to the persons with a case manager (36%). Reasons for not initiating care were reluctancy of the persons with YOD or their caregivers, the person deceased, or because the GP did not refer for care. CONCLUSION: Care use differed between persons due to different needs and reasons. Although most persons with YOD receive care in the years after diagnosis, there are still factors that could be improved.

Pre-Diagnostic Symptoms of Young-Onset Dementia in the General Practice up to Five Years Before Diagnosis.

BACKGROUND: Young-onset dementia (YOD) has many underlying etiologies, leading to a large heterogeneity in first symptoms. This makes it difficult for general practitioners (GPs) to recognize YOD. OBJECTIVE: Identify early symptoms that are more common in the pre-diagnostic phase of YOD. METHODS: We performed a case-control study nested in a primary-care registry on 89 cases and 162 matched controls, where we compared symptoms of people with YOD up to 5 years before diagnosis to their matched control group without YOD. The variables included in this study were International Classification of Primary Care codes and symptoms extracted from written GP notes and categorized in groups. We used Generalized Equation Estimation to analyze symptom's time-trajectories and logistic regression and ROC-curves to analyze differences in number of symptom categories reported. RESULTS: Cognitive symptoms were more common in people with YOD 5 years before diagnosis, affective symptoms 4 years before diagnosis, social symptoms 3 years, behavioral symptoms 2 years, and daily functioning disturbances 1 year before diagnosis. The ROC-curve suggested that reporting two or more symptom categories at the GP gave the best trade-off between sensitivity (85%) and specificity (77%), for the highest percentage of correctly diagnosed persons. CONCLUSION: This study showed people with YOD present differently than people without YOD. However, it may still be difficult for GPs to use these symptom categories to distinguish people with YOD, since the symptoms also occur in people with other diseases. A combination of reported symptom categories increases the probability of an underlying cause of YOD.

Temporal trends of sex differences for COVID-19 infection, hospitalisation, severe disease, intensive care unit (ICU) admission and death: a meta-analysis of 229 studies covering over 10M patients.

Background: This review aims to investigate the association of sex with the risk of multiple COVID-19 health outcomes, ranging from infection to death. Methods: Pubmed and Embase were searched through September 2020. We considered studies reporting sex and coronavirus disease 2019 (COVID-19) outcomes. Qualitative and quantitative data were extracted using standardised electronic data extraction forms with the assessment of Newcastle Ottawa Scale for risk of bias. Pooled trends in infection, hospitalization, severity, intensive care unit (ICU) admission and death rate were calculated separately for men and women and subsequently random-effects meta-analyses on relative risks (RR) for sex was performed. Results: Of 10,160 titles, 229 studies comprising 10,417,452 patients were included in the analyses. Methodological quality of the included studies was high (6.9 out of 9). Men had a higher risk for infection with COVID-19 than women (RR = 1.14, 95%CI: 1.07 to 1.21). When infected, they also had a higher risk for hospitalization (RR = 1.33, 95%CI: 1.27 to 1.41), higher risk for severe COVID-19 (RR = 1.22, 95%CI: 1.17 to 1.27), higher need for Intensive Care (RR = 1.41, 95%CI: 1.28 to 1.55), and higher risk of death (RR = 1.35, 95%CI: 1.28 to 1.43). Within the period studied, the RR for infection and severity increased for men compared to women, while the RR for mortality decreased for men compared to women. Conclusions: Meta-analyses on 229 studies comprising over 10 million patients showed that men have a higher risk for COVID-19 infection, hospitalization, disease severity, ICU admission and death. The relative risks of infection, disease severity and death for men versus women showed temporal trends with lower relative risks for infection and severity of disease and higher relative risk for death at the beginning of the pandemic compared to the end of our inclusion period. PROSPERO registration: CRD42020180085 (20/04/2020).

Ethnic minority status as social determinant for COVID-19 infection, hospitalisation, severity, ICU admission and deaths in the early phase of the pandemic: a meta-analysis.

INTRODUCTION: Early literature on the COVID-19 pandemic indicated striking ethnic inequalities in SARS-CoV-2-related outcomes. This systematic review and meta-analysis aimed to describe the presence and magnitude of associations between ethnic groups and COVID-19-related outcomes. METHODS: PubMed and Embase were searched from December 2019 through September 2020. Studies reporting extractable data (ie, crude numbers, and unadjusted or adjusted risk/ORs) by ethnic group on any of the five studied outcomes: confirmed COVID-19 infection in the general population, hospitalisation among infected patients, and disease severity, intensive care unit (ICU) admission and mortality among hospitalised patients with SARS-CoV-2 infection, were included using standardised electronic data extraction forms. We pooled data from published studies using random-effects meta-analysis. RESULTS: 58 studies were included from seven countries in four continents, mostly retrospective cohort studies, covering a total of almost 10 million individuals from the first wave until the summer of 2020. The risk of diagnosed SARS-CoV-2 infection was higher in most ethnic minority groups than their White counterparts in North American and Europe with the differences remaining in the US ethnic minorities after adjustment for confounders and explanatory factors. Among people with confirmed infection, African-Americans and Hispanic-Americans were also more likely than White-Americans to be hospitalised with SARS-CoV-2 infection. No increased risk of COVID-19 outcomes (ie, severe disease, ICU admission and death) was found among ethnic minority patients once hospitalised, except for a higher risk of death among ethnic minorities in Brazil. CONCLUSION: The risk of SARS-CoV-2 diagnosis was higher in most ethnic minorities, but once hospitalised, no clear inequalities exist in COVID-19 outcomes except for the high risk of death in ethnic minorities in Brazil. The findings highlight the necessity to tackle disparities in social determinants of health, preventative opportunities and delay in healthcare use. Ethnic minorities should specifically be considered in policies mitigating negative impacts of the pandemic. PROSPERO REGISTRATION NUMBER: CRD42020180085.

Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies.

OBJECTIVE: We aimed to describe the associations of age and sex with the risk of COVID-19 in different severity stages ranging from infection to death. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed and Embase through 4 May 2020. STUDY SELECTION: We considered cohort and case-control studies that evaluated differences in age and sex on the risk of COVID-19 infection, disease severity, intensive care unit (ICU) admission and death. DATA EXTRACTION AND SYNTHESIS: We screened and included studies using standardised electronic data extraction forms and we pooled data from published studies and data acquired by contacting authors using random effects meta-analysis. We assessed the risk of bias using the Newcastle-Ottawa Scale. RESULTS: We screened 11.550 titles and included 59 studies comprising 36.470 patients in the analyses. The methodological quality of the included papers was high (8.2 out of 9). Men had a higher risk for infection with COVID-19 than women (relative risk (RR) 1.08, 95% CI 1.03 to 1.12). When infected, they also had a higher risk for severe COVID-19 disease (RR 1.18, 95% CI 1.10 to 1.27), a higher need for intensive care (RR 1.38, 95% CI 1.09 to 1.74) and a higher risk of death (RR 1.50, 95% CI 1.18 to 1.91). The analyses also showed that patients aged 70 years and above have a higher infection risk (RR 1.65, 95% CI 1.50 to 1.81), a higher risk for severe COVID-19 disease (RR 2.05, 95% CI 1.27 to 3.32), a higher need for intensive care (RR 2.70, 95% CI 1.59 to 4.60) and a higher risk of death once infected (RR 3.61, 95% CI 2.70 to 4.84) compared with patients younger than 70 years. CONCLUSIONS: Meta-analyses on 59 studies comprising 36.470 patients showed that men and patients aged 70 and above have a higher risk for COVID-19 infection, severe disease, ICU admission and death. PROSPERO REGISTRATION NUMBER: CRD42020180085.

Global Prevalence of Young-Onset Dementia: A Systematic Review and Meta-analysis.

Importance: Reliable prevalence estimates are lacking for young-onset dementia (YOD), in which symptoms of dementia start before the age of 65 years. Such estimates are needed for policy makers to organize appropriate health care. Objective: To determine the global prevalence of YOD. Data Sources: The PubMed, Embase, CINAHL, and PsycInfo databases were systematically searched for population-based studies on the prevalence of YOD published between January 1, 1990, and March 31, 2020. Study Selection: Studies containing data on the prevalence of dementia in individuals younger than 65 years were screened by 2 researchers for inclusion in a systematic review and meta-analysis. Data Extraction and Synthesis: Prevalence estimates on 5-year age bands, from 30 to 34 years to 60 to 64 years, were extracted. Random-effects meta-analyses were conducted to pool prevalence estimates. Results were age standardized for the World Standard Population. Heterogeneity was assessed by subgroup analyses for sex, dementia subtype, study design, and economic status based on the World Bank classification and by meta-regression. Main Outcomes and Measures: Prevalence estimates of YOD for 5-year age bands. Results: A total of 95 unique studies were included in this systematic review, of which 74 with 2 760 379 unique patients were also included in 5-year age band meta-analyses. Studies were mostly conducted in Europe and in older groups in Asia, North America, and Oceania. Age-standardized prevalence estimates increased from 1.1 per 100 000 population in the group aged 30 to 34 years to 77.4 per 100 000 population in the group aged 60 to 64 years. This gives an overall global age-standardized prevalence of 119.0 per 100 000 population in the age range of 30 to 64 years, corresponding to 3.9 million people aged 30 to 64 years living with YOD in the world. Subgroup analyses showed prevalence between men and women to be similar (crude estimates for men, 216.5 per 100 000 population; for women, 293.1 per 100 000 population), whereas prevalence was lower in high-income countries (crude estimate, 663.9 per 100 000 population) compared with upper-middle-income (crude estimate, 1873.6 per 100 000 population) and lower-middle-income (crude estimate, 764.2 per 100 000 population) countries. Meta-regression showed that age range (P < .001), sample size (P < .001), and study methodology (P = .02) significantly influenced heterogeneity between studies. Conclusions and Relevance: This systematic review and meta-analysis found an age-standardized prevalence of YOD of 119.0 per 100 000 population, although estimates of the prevalence in low-income countries and younger age ranges remain scarce. These results should help policy makers organize sufficient health care for this subgroup of individuals with dementia. Study Registration: PROSPERO CRD42019119288.