Browsing by Author "Smith, Eric E."
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Item Open Access Cerebral Small Vessel Disease: Cognitive Reserve and Mediators of Cognitive Decline(2021-09-24) Durrani, Romella; Smith, Eric E.; Ismail, Zahinoor; Hill, Michael D.; Monchi, Oury; Dukelow, Sean P.; Postuma, Ronald B.Background: Cerebral small vessel disease (CSVD) is the most common type of cerebrovascular disease that contributes to cognitive decline and dementia. However, persons with the same burden of CSVD often have different cognitive outcomes. Cognitive reserve, defined as the ability to tolerate or adapt to pathology, has been suggested to explain these variations. There are limited studies on cognitive reserve in CSVD, as most studies have focused on Alzheimer’s disease (AD). These studies have also focused on education as the proxy of cognitive reserve, with only a few studies looking at other proxies, such as occupation and leisure activities. Additionally, few studies of cognitive reserve have examined other measures of cerebrovascular disease, beyond white matter hyperintensities (WMH). Objectives: Determine whether cognitive reserve mitigates the deleterious effects of CSVD on cognition, and determine the degree to which cerebral amyloid angiopathy (CAA) biomarkers mediate the effects of CAA on cognition.Methods: Data were analyzed from four multicenter, cross-sectional cohorts. Measures of cerebrovascular disease included: brain infarcts, non-lacunar covert brain infarcts (CBI), WMH, vascular lesion burden, and CAA. Measures of cognitive reserve included: education, occupation, social involvement, physical activity, leisure physical activity, household income, marital status, height, stress, and multilingualism. CAA biomarkers included: WMH, cerebrovascular reactivity (CVR), peak width of skeletonized mean diffusivity (PSMD), mean cortical thickness, and mean cortical thickness in an AD meta-region of interest.Results: WMH, non-lacunar CBI, vascular lesion burden, and CAA were associated with lower cognition. Proxies of cognitive reserve were associated with higher cognition. However, cognitive reserve did not modify the association between CSVD and cognition. CVR, PSMD, and mean cortical thickness in regions typically affected by AD accounted for half of the effects of CAA on cognition; PSMD was the largest contributor.Conclusions: This forms the largest body of work on cognitive reserve within CSVD. Strategies to prevent CSVD-related cognitive decline and dementia include: 1) preventing CSVD, 2) enhancing cognitive reserve, thereby independently increasing cognition---however, this does not mitigate the deleterious effects of CSVD on cognition, and 3) in CAA, maintaining white matter integrity and restoring normal cerebrovascular reactivity.Item Open Access Characterizing Plasma Biomarkers of Cerebral Amyloid Angiopathy(2024-07-26) Muir, Ryan Thomas; Smith, Eric E.; Hill, Michael D.; Black, Sandra E.; Hsuing, RobinBACKGROUND: Cerebral Amyloid Angiopathy (CAA) is characterized by the progressive deposition of beta-amyloid in cortical and leptomeningeal small vessels leading to hemorrhagic stroke and dementia. While CAA is diagnosed using Boston Criteria 2.0, they are not always possible to apply. Plasma biomarkers (Aβ42, Aβ40, phosphorylated-tau (p-tau), neurofilament light chain (NfL) and Glial Fibrillary Acidic Protein (GFAP)) might improve diagnostic accuracy. This study evaluates whether plasma biomarkers: (i) differ in CAA compared to controls (ii) discriminate a diagnosis of CAA individually and in combination and (iii) are associated with cognition and neuroimaging biomarkers. METHODS: Data are from a multi-centre cohort study of participants with probable CAA and healthy controls. Participants had plasma collected and underwent neurocognitive evaluation and magnetic resonance imaging. Aβ was quantified with two independent methods: immunoprecipitation mass-spectrometry (IPMS) and single molecule array assay (Simoa). Plasma p-tau181, NfL and GFAP were quantified with Simoa. Neuroimaging biomarkers of small vessel disease, atrophy, white matter integrity and cerebrovascular reactivity (CVR) were quantified. Logistic regression was used to compute areas under the receiver operating characteristic curve (AUC) to assess biomarker discriminative performance of ascertaining a diagnosis of CAA. Associations between plasma biomarkers, cognition and neuroimaging biomarkers were evaluated with generalized linear models. RESULTS: 45 participants with CAA and 47 controls were eligible. With both methods, the Aβ42/40 ratio was reduced in CAA compared to controls. Furthermore, those with CAA had elevated p-tau181 and NfL. A combination of Aβ42/40 (Simoa), p-tau181, and NfL resulted in an AUC of 0.90. Reduced Aβ42/40 was associated with poorer speed of processing. Increasing NfL was associated with reduced Montreal Cognitive Assessment Scores, lower CVR and increasing CAA severity. CONCLUSIONS: This study identified differences in plasma Aβ42/40, p-tau181 and NfL in CAA compared and provides evidence that a panel of these biomarkers can achieve excellent diagnostic discriminability. This study also demonstrates that a marker of cerebral amyloidosis (Aβ42/40) is associated with speed of processing difficulties in those with CAA, while NfL was associated with global cognition, CAA severity and CVR. Overall, plasma biomarkers might, in future, help improve the evaluation and detection of CAA.Item Open Access Dementia risk prediction in individuals with mild cognitive impairment: a comparison of Cox regression and machine learning models(2022-11-02) Wang, Meng; Greenberg, Matthew; Forkert, Nils D.; Chekouo, Thierry; Afriyie, Gabriel; Ismail, Zahinoor; Smith, Eric E.; Sajobi, Tolulope T.Abstract Background Cox proportional hazards regression models and machine learning models are widely used for predicting the risk of dementia. Existing comparisons of these models have mostly been based on empirical datasets and have yielded mixed results. This study examines the accuracy of various machine learning and of the Cox regression models for predicting time-to-event outcomes using Monte Carlo simulation in people with mild cognitive impairment (MCI). Methods The predictive accuracy of nine time-to-event regression and machine learning models were investigated. These models include Cox regression, penalized Cox regression (with Ridge, LASSO, and elastic net penalties), survival trees, random survival forests, survival support vector machines, artificial neural networks, and extreme gradient boosting. Simulation data were generated using study design and data characteristics of a clinical registry and a large community-based registry of patients with MCI. The predictive performance of these models was evaluated based on three-fold cross-validation via Harrell’s concordance index (c-index), integrated calibration index (ICI), and integrated brier score (IBS). Results Cox regression and machine learning model had comparable predictive accuracy across three different performance metrics and data-analytic conditions. The estimated c-index values for Cox regression, random survival forests, and extreme gradient boosting were 0.70, 0.69 and 0.70, respectively, when the data were generated from a Cox regression model in a large sample-size conditions. In contrast, the estimated c-index values for these models were 0.64, 0.64, and 0.65 when the data were generated from a random survival forest in a large sample size conditions. Both Cox regression and random survival forest had the lowest ICI values (0.12 for a large sample size and 0.18 for a small sample size) among all the investigated models regardless of sample size and data generating model. Conclusion Cox regression models have comparable, and sometimes better predictive performance, than more complex machine learning models. We recommend that the choice among these models should be guided by important considerations for research hypotheses, model interpretability, and type of data.Item Open Access Effects of aging on the association between cerebrovascular responses to visual stimulation, hypercapnia and arterial stiffness(Frontiers, 2014-02-19) Fluck, Daniela; Beaudin, Andrew E.; Steinback, Craig D.; Kumparpillai, Gopukumar; Shobha, Nandavar; McCreary, Cheryl R.; Peca, Stefano; Smith, Eric E.; Poulin, Marc J.Item Open Access Neuroimaging Correlates of Gait Control in Cerebral Amyloid Angiopathy(2023-01-16) Sharma, Breni; Smith, Eric E.; Harris, Ashley; Ismail, Zahinoor; McCreary, Cheryl R.Cerebral amyloid angiopathy (CAA) is the second most common subtype of cerebral small vessel disease (CSVD) and is characterized by the buildup of beta-amyloid protein in the walls of small-medium sized arteries and arterioles of the leptomeninges. Much is known about common clinical manifestations of the disease, such as presence of white matter hyperintensities, lacunar infarcts, cerebral microbleeds, cortical superficial siderosis, and phenotypic presentations, such as the cognitive profile of CAA and its contribution to neurodegeneration and dementia. However, little had been known about the gait profile of CAA or the neural correlates underlying any abnormalities observed, such as grey matter atrophy, white matter damage, or brain iron accumulation. To address these gaps in the literature, I first conducted a systematic review and meta-analysis of the existing literature covering CSVD and its relation to gait and falls. Once evident that gait difficulties were a feature of CSVD as a whole, I examined gait abilities of patients with CAA, when compared to normal controls (NC), patients with Alzheimer’s disease (AD), and mild cognitive impairment (MCI). With this, I also looked at associations with falls history and fear of falling, as well as the relationships between gait ability and cognition, WMH volume, and CMB count. Significant gait impairments were found in CAA, prompting an examination of associations between these impairments and grey and white matter damage and iron content in select brain regions. In CSVD, there was a general consensus across studies of an association between greater CSVD burden and worse gait and greater falls. Looking specifically at CAA, significant impairments were found in gait compared to NC but not to AD. Further investigation of this lead to associations between worse gait and grey matter atrophy in frontal, AD-affected, and subcortical regions and with greater white matter structural damage. Iron content, however, did not differ between CAA and NC. Overall, gait appears to be negatively impacted by CAA pathology. Further examination of neural correlates may help to better understand the disease and incorporation of the current findings may help to inform clinicians on the functional outcomes of CAA patients.Item Open Access Normal sex and age-specific parameters in a multi-ethnic population: a cardiovascular magnetic resonance study of the Canadian Alliance for Healthy Hearts and Minds cohort(2022-01-03) Luu, Judy M.; Gebhard, Catherine; Ramasundarahettige, Chinthanie; Desai, Dipika; Schulze, Karleen; Marcotte, Francois; Awadalla, Philip; Broet, Philippe; Dummer, Trevor; Hicks, Jason; Larose, Eric; Moody, Alan; Smith, Eric E.; Tardif, Jean-Claude; Teixeira, Tiago; Teo, Koon K.; Vena, Jennifer; Lee, Douglas S.; Anand, Sonia S.; Friedrich, Matthias G.Abstract Background Despite the growing utility of cardiovascular magnetic resonance (CMR) for cardiac morphology and function, sex and age-specific normal reference values derived from large, multi-ethnic data sets are lacking. Furthermore, most available studies use a simplified tracing methodology. Using a large cohort of participants without history of cardiovascular disease (CVD) or risk factors from the Canadian Alliance for Healthy Heart and Minds, we sought to establish a robust set of reference values for ventricular and atrial parameters using an anatomically correct contouring method, and to determine the influence of age and sex on ventricular parameters. Methods and results Participants (n = 3206, 65% females; age 55.2 ± 8.4 years for females and 55.1 ± 8.8 years for men) underwent CMR using standard methods for quantitative measurements of cardiac parameters. Normal ventricular and atrial reference values are provided: (1) for males and females, (2) stratified by four age categories, and (3) for different races/ethnicities. Values are reported as absolute, indexed to body surface area, or height. Ventricular volumes and mass were significantly larger for males than females (p < 0.001). Ventricular ejection fraction was significantly diminished in males as compared to females (p < 0.001). Indexed left ventricular (LV) end-systolic, end-diastolic volumes, mass and right ventricular (RV) parameters significantly decreased as age increased for both sexes (p < 0.001). For females, but not men, mean LV and RVEF significantly increased with age (p < 0.001). Conclusion Using anatomically correct contouring methodology, we provide accurate sex and age-specific normal reference values for CMR parameters derived from the largest, multi-ethnic population free of CVD to date. Clinical trial registration ClinicalTrials.gov, NCT02220582. Registered 20 August 2014—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02220582 .Item Open Access Optimizing detection of Alzheimer’s disease in mild cognitive impairment: a 4-year biomarker study of mild behavioral impairment in ADNI and MEMENTO(2023-07-29) Ismail, Zahinoor; Leon, Rebeca; Creese, Byron; Ballard, Clive; Robert, Philippe; Smith, Eric E.Abstract Background Disease-modifying drug use necessitates better Alzheimer disease (AD) detection. Mild cognitive impairment (MCI) leverages cognitive decline to identify the risk group; similarly, mild behavioral impairment (MBI) leverages behavioral change. Adding MBI to MCI improves dementia prognostication over conventional approaches of incorporating neuropsychiatric symptoms (NPS). Here, to determine if adding MBI would better identify AD, we interrogated associations between MBI in MCI, and cerebrospinal fluid biomarkers [β-amyloid (Aβ), phosphorylated-tau (p-tau), and total-tau (tau)-ATN], cross-sectionally and longitudinally. Methods Data were from two independent referral-based cohorts, ADNI (mean[SD] follow-up 3.14[1.07] years) and MEMENTO (4.25[1.40] years), collected 2003–2021. Exposure was based on three-group stratification: 1) NPS meeting MBI criteria; 2) conventionally measured NPS (NPSnotMBI); and 3) noNPS. Cohorts were analyzed separately for: 1) cross-sectional associations between NPS status and ATN biomarkers (linear regressions); 2) 4-year longitudinal repeated-measures associations of MBI and NPSnotMBI with ATN biomarkers (hierarchical linear mixed-effects models-LMEs); and 3) rates of incident dementia (Cox proportional hazards regressions). Results Of 510 MCI participants, 352 were from ADNI (43.5% females; mean [SD] age, 71.68 [7.40] years), and 158 from MEMENTO (46.2% females; 68.98 [8.18] years). In ADNI, MBI was associated with lower Aβ42 (standardized β [95%CI], -5.52% [-10.48-(-0.29)%]; p = 0.039), and Aβ42/40 (p = 0.01); higher p-tau (9.67% [3.96–15.70%]; p = 0.001), t-tau (7.71% [2.70–12.97%]; p = 0.002), p-tau/Aβ42 (p < 0.001), and t-tau/Aβ42 (p = 0.001). NPSnotMBI was associated only with lower Aβ42/40 (p = 0.045). LMEs revealed a similar 4-year AD-specific biomarker profile for MBI, with NPSnotMBI associated only with higher t-tau. MBI had a greater rate of incident dementia (HR [95%CI], 3.50 [1.99–6.17; p < 0.001). NPSnotMBI did not differ from noNPS (HR 0.96 [0.49–1.89]; p = 0.916). In MEMENTO, MBI demonstrated a similar magnitude and direction of effect for all biomarkers, but with a greater reduction in Aβ40. HR for incident dementia was 3.93 (p = 0.004) in MBI, and 1.83 (p = 0.266) in NPSnotMBI. Of MBI progressors to dementia, 81% developed AD dementia. Conclusions These findings support a biological basis for NPS that meet MBI criteria, the continued inclusion of MBI in NIA-AA ATN clinical staging, and the utility of MBI criteria to improve identification of patients for enrollment in disease-modifying drug trials or for clinical care.Item Open Access Repurposing repeated remote ischemic postconditioning for multiple sclerosis(2023-09-20) Tottenham, Isabelle Elaine Louise; Camara-Lemarroy, Carlos; Yong, V. Wee; Ousman, Shalina; Smith, Eric E.Multiple sclerosis (MS) is a chronic, autoimmune neurodegenerative disease that is characterized by nervous system demyelination and heterogenous disability. Current disease modifying treatments accessible to Canadians are limited because they are primarily targeting the neuroinflammatory component of the disease, not the neurodegenerative component. There is a need for focus on development of therapies that target the demyelinating insults that people with MS experience. In this study, we evaluate the use of repeated remote ischemic postconditioning (RIC) as a therapeutic target for promoting white matter repair and protection. Due to the novelty of the intervention in the MS field, we first wanted to identify transcriptomic and proteomic changes to the spinal cord with repeated RIC. We found that targets involved in antioxidant, protein synthesis, angiogenesis, axonogenesis, and remyelination pathways (among others) were upregulated with 14 days of consecutive RIC. Using a focal demyelinating mouse model, we also described changes to the lesion environment using the repeated intervention. Repeated RIC did not reduce the lesion size in this injury model. However, targets such as plectin and neurofascin that were upregulated in the transcriptomic and proteomic data sets were also upregulated in the lesion of animals that received treatment. An increase in myelin in the lesion area was also found in the repeated RIC group when compared to sham. Overall, repeated RIC demonstrates potential for future use as a therapy to target white matter repair and protection.Item Open Access Sex differences in direct healthcare costs following stroke: a population-based cohort study(2021-06-29) Yu, Amy Y. X.; Krahn, Murray; Austin, Peter C.; Rashid, Mohammed; Fang, Jiming; Porter, Joan; Vyas, Manav V.; Bronskill, Susan E.; Smith, Eric E.; Swartz, Richard H.; Kapral, Moira K.Abstract Background The economic burden of stroke on the healthcare system has been previously described, but sex differences in healthcare costs have not been well characterized. We described the direct person-level healthcare cost in men and women as well as the various health settings in which costs were incurred following stroke. Methods In this population-based cohort study of patients admitted to hospital with stroke between 2008 and 2017 in Ontario, Canada, we used linked administrative data to calculate direct person-level costs in Canadian dollars in the one-year following stroke. We used a generalized linear model with a gamma distribution and a log link function to compare costs in women and men with and without adjustment for baseline clinical differences. We also assessed for an interaction between age and sex using restricted cubic splines to model the association of age with costs. Results We identified 101,252 patients (49% were women, median age [Q1-Q3] was 76 years [65–84]). Unadjusted costs following stroke were higher in women compared to men (mean ± standard deviation cost was $54,012 ± 54,766 for women versus $52,829 ± 59,955 for men, and median cost was $36,703 [$16,496–$72,227] for women versus $32,903 [$15,485–$66,007] for men). However, after adjustment, women had 3% lower costs compared to men (relative cost ratio and 95% confidence interval 0.97 [0.96,0.98]). The lower cost in women compared to men was most prominent among people aged over 85 years (p for interaction = 0.03). Women incurred lower costs than men in outpatient care and rehabilitation, but higher costs in complex continuing care, long-term care, and home care. Conclusions Patterns of resource utilization and direct medical costs were different between men and women after stroke. Our findings inform public payers of the drivers of costs following stroke and suggest the need for sex-based cost-effectiveness evaluation of stroke interventions with consideration of costs in all care settings.Item Open Access The impact of reporting magnetic resonance imaging incidental findings in the Canadian alliance for healthy hearts and minds cohort(2021-10-28) Luu, Judy M.; Sergeant, Anand K.; Anand, Sonia S.; Desai, Dipika; Schulze, Karleen; Knoppers, Bartha M.; Zawati, Ma’n H.; Smith, Eric E.; Moody, Alan R.; Black, Sandra E.; Larose, Eric; Marcotte, Francois; Kleiderman, Erika; Tardif, Jean-Claude; Lee, Douglas S.; Friedrich, Matthias G.Abstract Background In the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies. Methods Between 2013 and 2019, 8252 participants (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported. Results Severe structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy. Conclusion The management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT02220582 .Item Open Access The Prevalence and Incidence of Dementia Due to Alzheimer's Disease: a Systematic Review and Meta-Analysis(CAMBRIDGE UNIV PRESS, 2016) Fiest, Kirsten M.; Roberts, Jodie I.; Maxwell, Colleen J.; Hogan, David B.; Smith, Eric E.; Frolkis, Alexandra; Cohen, Adrienne; Kirk, Andrew; Pearson, Dawn; Pringsheim, Tamara; Venegas-Torres, Andres; Jette, NathalieBackground: Updated information on the epidemiology of dementia due to Alzheimer's disease (AD) is needed to ensure that adequate resources are available to meet current and future healthcare needs. We conducted a systematic review and meta-analysis of the incidence and prevalence of AD. Methods: The MEDLINE and EMBASE databases were searched from 1985 to 2012, as well as the reference lists of selected articles. Included articles had to provide an original population-based estimate for the incidence and/or prevalence of AD. Two individuals independently performed abstract and full-text reviews, data extraction and quality assessments. Random-effects models were employed to generate pooled estimates stratified by age, sex, diagnostic criteria, location (i.e., continent) and time (i.e., when the study was done). Results: Of 16,066 abstracts screened, 707 articles were selected for full-text review. A total of 119 studies met the inclusion criteria. In community settings, the overall point prevalence of dementia due to AD among individuals 60 + was 40.2 per 1000 persons (CI95%: 29.1-55.6), and pooled annual period prevalence was 30.4 per 1000 persons (CI95%: 15.6-59.1). In community settings, the overall pooled annual incidence proportion of dementia due to AD among individuals 60 + was 34.1 per 1000 persons (CI95%: 16.4-70.9), and the incidence rate was 15.8 per 1000 person-years (CI95%: 12.9-19.4). Estimates varied significantly with age, diagnostic criteria used and location (i.e., continent). Conclusions: The burden of AD dementia is substantial. Significant gaps in our understanding of its epidemiology were identified, even in a high-income country such as Canada. Future studies should assess the impact of using such newer clinical diagnostic criteria for AD dementia such as those of the National Institute on Aging-Alzheimer's Association and/or incorporate validated biomarkers to confirm the presence of Alzheimer pathology to produce more precise estimates of the global burden of AD.Item Open Access The Prevalence and Incidence of Dementia: a Systematic Review and Meta-analysis(CAMBRIDGE UNIV PRESS, 2016) Fiest, Kirsten M.; Jette, Nathalie; Roberts, Jodie I.; Maxwell, Colleen J.; Smith, Eric E.; Black, Sandra E.; Blaikie, Laura; Cohen, Adrienne; Day, Lundy; Holroyd-Leduc, Jayna; Kirk, Andrew; Pearson, Dawn; Pringsheim, Tamara; Venegas-Torres, Andres; Hogan, David B.Introduction: Dementia is a common neurological condition affecting many older individuals that leads to a loss of independence, diminished quality of life, premature mortality, caregiver burden and high levels of healthcare utilization and cost. This is an updated systematic review and meta-analysis of the worldwide prevalence and incidence of dementia. Methods: The MEDLINE and EMBASE databases were searched for relevant studies published between 2000 (1985 for Canadian papers) and July of 2012. Papers selected for full-text review were included in the systematic review if they provided an original population-based estimate for the incidence and/or prevalence of dementia. The reference lists of included articles were also searched for additional studies. Two individuals independently performed abstract and full-text review, data extraction, and quality assessment of the papers. Random-effects models and/or meta-regression were used to generate pooled estimates by age, sex, setting (i.e., community, institution, both), diagnostic criteria utilized, location (i.e., continent) and year of data collection. Results: Of 16,066 abstracts screened, 707 articles were selected for full-text review. A total of 160 studies met the inclusion criteria. Among individuals 60 and over residing in the community, the pooled point and annual period prevalence estimates of dementia were 48.62 (CI95%: 41.98-56.32) and 69.07 (CI95%: 52.36-91.11) per 1000 persons, respectively. The respective pooled incidence rate (same age and setting) was 17.18 (CI95%: 13.90-21.23) per 1000 person-years, while the annual incidence proportion was 52.85 (CI95%: 33.08-84.42) per 1,000 persons. Increasing participant age was associated with a higher dementia prevalence and incidence. Annual period prevalence was higher in North America than in South America, Europe and Asia (in order of decreasing period prevalence) and higher in institutional compared to community and combined settings. Sex, diagnostic criteria (except for incidence proportion) and year of data collection were not associated with statistically significant different estimates of prevalence or incidence, though estimates were consistently higher for females than males. Conclusions: Dementia is a common neurological condition in older individuals. Significant gaps in knowledge about its epidemiology were identified, particularly with regard to the incidence of dementia in low- and middle-income countries. Accurate estimates of prevalence and incidence of dementia are needed to plan for the health and social services that will be required to deal with an aging population.Item Open Access The Prevalence and Incidence of Frontotemporal Dementia: a Systematic Review(CAMBRIDGE UNIV PRESS, 2016) Hogan, David B.; Jette, Nathalie; Fiest, Kirsten M.; Roberts, Jodie I.; Pearson, Dawn; Smith, Eric E.; Pamela Roach; Kirk, Andrew; Pringsheim, Tamara; Maxwell, Colleen J.Background Population-based prevalence and incidence studies are essential for understanding the burden of frontotemporal dementia (FTD). Methods The MEDLINE and EMBASE databases were searched to identify population-based publications from 1985 to 2012, addressing the incidence and/or prevalence of FTD. References of included articles and prior systematic reviews were searched for additional studies. Two reviewers screened all abstracts and full-text reviews, abstracted data and performed quality assessments. Results Twenty-six studies were included. Methodological limitations led to wide ranges in the estimates for prevalence (point prevalence 0.01-4.6 per 1000 persons; period prevalence 0.16-31.04 per 1000 persons) and incidence (0.0-0.3 per 1000 person-years). FTD accounted for an average of 2.7% (range 0-9.1%) of all dementia cases among prevalence studies that included subjects 65 and older compared to 10.2% (range 2.8-15.7%) in studies restricted to those aged less than 65. The cumulative numbers of male (373 [52.5%]) and female (338 [47.5%]) cases from studies reporting this information were nearly equal (p=0.18). The behavioural variant FTD (bvFTD) was almost four times as common as the primary progressive aphasias. Conclusions Population-based estimates for the epidemiology of FTD varied widely in the included studies. Refinements in the diagnostic process, possibly by the use of validated biomarkers or limiting case ascertainment to specialty services, are needed to obtain more precise estimates of the prevalence and incidence of FTD.