High burden of neurological disease in the older general population: results from the Canadian Longitudinal Study on Aging.

BACKGROUND AND PURPOSE: Our objective was to study the association between the presence of a neurological disease and the comorbidity burden as well as healthcare utilization (HCU). METHODS: Using baseline data from the Canadian Longitudinal Study on Aging (CLSA), we examined the burden of five neurological conditions. The CLSA is a population-based study of approximately 50 000 individuals, aged 45-85 years at baseline. We used multivariable Poisson regression to identify correlates of comorbidity burden and HCU. RESULTS: The lifetime prevalence of five neurological diseases is presented: epilepsy, Parkinson's disease/parkinsonism, stroke/transient ischaemic attack, multiple sclerosis and migraine. We found the somatic and psychiatric comorbidity burden to be higher in those individuals with a neurological disease (an 18-45% mean increase in the number of chronic conditions) as compared with the comparison group without a neurological disease, except for Parkinson's disease/parkinsonism. The presence of a neurological disease was associated with only a modest increase in the probability of visiting a general practitioner but was associated with a greatly increased probability of visiting a medical specialist (up to 68% more likely) or an emergency department (up to 79% more likely) and an overnight hospitalization (up to 108% more likely). CONCLUSIONS: We found striking associations between our neurological diseases and increased comorbidity burdens and HCU. These findings are important for informing public policy planning as well as driving avenues for future research. The present study established the CLSA as an important research platform for the study of neurological conditions in an aging general population.

The diagnostic accuracy of routine electroencephalography after a first unprovoked seizure.

The clinical utility of routine electroencephalography (EEG) after a first unprovoked seizure remains uncertain. Its diagnostic accuracy in identifying adults and children with new onset epilepsy was examined. A systematic review and meta-analysis of studies examining individuals who underwent routine EEG after a first unprovoked seizure and were followed for seizure recurrence for at least 1 year was performed. A 'positive' test was defined by the presence of epileptiform discharges (ED). Pooled sensitivity and specificity estimates were calculated using a bivariate random effects regression model. In all, 3096 records were reviewed, from which 15 studies were extracted with a total of 1799 participants. Amongst adult studies, the sensitivity and specificity (95% confidence interval) of routine EEG were 17.3% (7.9, 33.8) and 94.7% (73.7, 99.1), respectively. Amongst child studies, the pooled sensitivity and specificity were 57.8% (49.7, 65.6) and 69.6% (57.5, 79.5), respectively. Based upon our positive likelihood ratios, and assuming a pre-test probability of 50%, an adult with ED on routine EEG after a first unprovoked seizure has a 77% probability of having a second seizure, whilst a child with similar findings has a 66% probability. Further studies are required to examine the impact of patient characteristics and EEG features on the diagnostic accuracy of routine EEG for new onset epilepsy.

Does low socioeconomic status in early life protect against multiple sclerosis? A multinational, case-control study.

BACKGROUND AND PURPOSE: The findings from existing research on the association between socioeconomic status (SES) and multiple sclerosis (MS) are inconsistent. Most previous studies are limited to one country and do not adequately adjust for other risk factors for the disease. METHODS: The association between SES and MS was examined using data from the multinational Environmental Risk Factors in Multiple Sclerosis (EnvIMS) case-control study, comprising 2144 cases and 3859 controls from Norway, Canada and Italy. Multiple logistic regression was used to estimate the odds ratios and 95% confidence intervals for the association between early life SES, measured by parental educational level, and MS. Analyses were adjusted for age, sex, sunlight exposure, history of infectious mononucleosis, smoking, obesity and family size. RESULTS: Relative to those whose parents had primary school education or below, the adjusted odds ratio (95% confidence interval) for MS amongst individuals with university-educated parents, and the P value for trend across education levels, were 1.45 (1.03-2.05) in Canada (P for trend 0.030), 1.09 (0.85-1.39) in Norway (P for trend 0.395) and 0.65 (0.39-1.07) in Italy (P for trend 0.158). CONCLUSION: There is no consistent association between parental SES and MS risk in Norway, Canada and Italy, with a protective effect of low SES only found in Canada.

Is high socioeconomic status a risk factor for multiple sclerosis? A systematic review.

High socioeconomic status (SES) is generally associated with better health outcomes, but some research has linked it with an increased risk of multiple sclerosis (MS). The evidence for this association is inconsistent and has not previously been systematically reviewed. A systematic review of cohort and case-control studies in any language was conducted looking at the association between MS and SES. MEDLINE and EMBASE were searched for articles in all languages published up until 23 August 2013. Twenty-one studies from 13 countries were included in the review. Heterogeneity of study settings precluded carrying out a meta-analysis, and a qualitative synthesis was performed instead. Five studies, all from more unequal countries, reported an association between high SES and MS. Thirteen studies reported no evidence of an association, and three studies reported an association with low SES. These 16 studies largely came from more egalitarian countries. The evidence for an association between high SES and increased MS risk is inconsistent but with some indication of a stronger effect in countries and time periods with higher inequality. Firm conclusions are hampered by the failure of most studies to control for other important risk factors for MS.

Treatment comfort of adult neurologists in childhood onset conditions.

BACKGROUND: The majority of children with chronic neurodevelopmental disabilities are surviving to adulthood. Our goal was to assess how prepared and comfortable adult neurologists are in treating young adults with childhood onset chronic neurological conditions and evaluate the difficulty pediatric neurologists experience when transferring these patients to adult care. METHODS: We conducted a cross-sectional study using two postal surveys of all pediatric and adult neurologists in the province of Quebec, Canada. RESULTS: The response rate was 51.5%, with 119 neurologists completing the survey. Half of neurologists agreed that adult neurologists may not have adequate training in childhood onset disorders to prepare them to manage the disorders in adulthood, and 60% of pediatric neurologists reported having difficulty finding an adult provider for their patients. Adult neurologists were least comfortable treating patients with autism, chromosomal or metabolic disorders, and cognitive or behavioral disorders. CONCLUSION: Almost half of those surveyed believed that adult neurologists are not adequately trained to care for this growing patient population. Improving treatment comfort and knowledge among adult neurologists in childhood onset chronic neurological conditions may smooth the transition of these young adults from pediatric to adult care.

Quality of life during the course of cancer treatment in older newly diagnosed patients. Results of a prospective pilot study.

BACKGROUND: The aim of this prospective study was to report the quality of life (QoL) of older cancer patients during the first year after diagnosis and factors influencing QoL. PATIENTS AND METHODS: Newly diagnosed patients aged ≥65 years were recruited for a pilot prospective cohort study at the Jewish General Hospital, Montreal, Canada. Participants were interviewed at baseline, and at 1.5, 3, 4.5, 6, and 12 months. QoL was assessed at each interview using the European Organization for the Research and Treatment of Cancer Quality of Life Core Questionnaire with 30 items. Logistic regression was conducted to determine which sociodemographic, health, and functional status characteristics were associated with decline in global health status/QoL between baseline and 12-month follow-up. RESULTS: There were 112 participants at baseline (response rate 72%), median age of 74.1, and 70% were women. Between baseline and 12-month follow-up (n=78), 18 participants (23.1%) declined ≥10 points in global health status/QoL, while 34 participants (43.6%) remained stable and 23 participants (33.3%) improved ≥10 points. None of the sociodemographic, health, and functional status variables were associated with decline in logistic regression analyses. CONCLUSION: Almost 25% of older adults experienced clinically relevant decline in their QoL. Further research is needed on which factors influence decline in QoL in older adults.

Incidence and prevalence of amyotrophic lateral sclerosis in Canada: a systematic review of the literature.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease of unknown etiology. Although known to be rare, precise information on the frequency of ALS is essential to anticipate future demands on health resources and as baseline information for epidemiological studies. As part of a new ALS epidemiological initiative in Canada, we conducted a systematic review of published incidence and prevalence research in Canada. METHODS: Electronic searches and bibliographic reviews of pertinent publications were conducted. RESULTS: We identified 6 published studies from 4 Canadian provinces conducted between 1974 and 2004; 2 were available only as abstracts. Reported annual incidence rates were similar and study quality was generally good, but there was insufficient detail to adequately assess the methodological quality of 3 of the studies. The most recent studies reported an annual ALS age-adjusted incidence of 2.13 per 100,000 in Nova Scotia (2003-2004) and a crude mean annual incidence of 2.4 per 100,000 in Newfoundland and Labrador (2000-2004). CONCLUSIONS: There are limited data on the frequency of ALS in Canada. We found no studies from 6 of the Canadian provinces or from the territories. Future research is needed to estimate the frequency of occurrence of ALS in Canada.

Environmental risk factors in multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) likely results from an interaction between genetic and exogenous factors. While genetics shapes the overall population MS susceptibility, observed epidemiological patterns strongly suggest a role for the environment in disease initiation and modulation. RESULTS: Findings from studies on seasonality in MS patients' birth, disease onset and exacerbations, as well as apparent temporal trends in incidence and gender ratio support an influential effect of viruses, metabolic and lifestyle factors on MS risk. Epstein-Barr virus, vitamin D status, and smoking are factors that may explain such epidemiological patterns. CONCLUSIONS: Further epidemiological investigations are encouraged and opportunities to use data from existing cohort studies as well as the design of new studies should be pursued. In particular, the development of new large multicentre population-based case-control studies which incorporate the study of the role of environment and genetics, including epigenetic mechanisms, in determining MS risk is proposed.

Observer variation in the interpretation of xeromammograms.

We have examined variation in the interpretation of xeromammograms among radiologists designated to take part in a Canadian multicenter randomized controlled trial of screening for breast cancer. Radiologists read 100 xeromammograms comprising 10 histologically proved cancers, 40 benign abnormalities, and 50 normal films. Radiologists' opinions differed widely on the frequency of suspected or identified cancer. The diagnostic category "suspicion of cancer" or "cancer" was selected by radiologists for 10-55% of the films, and biopsy or aspiration was recommended for 21 to 53% of patients whose films were examined. Agreement on specific diagnostic categories was greatest for the diagnosis of cancer; agreement was least for the diagnosis of benign abnormalities and intermediate for the diagnosis of normality. Known cancers were in general correctly identified. These results indicate a need for development of methods to reduce observer variation in a interpretation of xeromammograms while preserving diagnostic sensitivity and validity. Results also emphasize the importance of developing strategies to ensure quality control in multicenter trials.

Comorbidity is associated with pain-related activity limitations in multiple sclerosis.

BACKGROUND: Comorbidities are common in multiple sclerosis (MS). The high prevalence of pain in MS is well-established but the influence of comorbidities on pain, specifically, pain-related interference in activity is not. OBJECTIVE: To examine the relationship between comorbidity and pain in MS. METHODS: We recruited 949 consecutive patients with definite MS from four Canadian centres. Participants completed the Health Utilities Index (HUI-Mark III) and a validated comorbidity questionnaire at 3 visits over 2 years. The HUI's pain scale was dichotomized into two groups: those with/without pain that disrupts normal activities. We used logistic regression to assess the association of pain with each comorbidity individually at baseline and over time. RESULTS: The incidence of disruptive pain over two years was 31.1 per 100 persons. Fibromyalgia, rheumatoid arthritis, irritable bowel syndrome, migraine, chronic lung disease, depression, anxiety, hypertension, and hypercholesterolemia were associated with disruptive pain (p<0.006). Individual-level effects on the presence of worsening pain were seen for chronic obstructive pulmonary disease (odds ratio [OR]: 1.50 95% CI: 1.08-2.09), anxiety (OR: 1.49 95% CI: 1.07-2.08), and autoimmune thyroid disease (OR: 1.40 95% CI: 1.00-1.97). CONCLUSION: Comorbidity is associated with pain in persons with MS. Closer examination of these associations may provide guidance for better management of this disabling symptom in MS.

The Canadian Neurological Scale: validation and reliability assessment.

The Canadian Neurological Scale (CNS) was designed to monitor mentation and motor functions in stroke patients. We assessed its validity and reliability on a group of 157 patients with a diagnosis of acute cerebrovascular accident. We determined validity by (1) correlating scale items and total score with the standard neurologic examination; (2) exploring the scale's predictive power with different end points at 6 months--the initial CNS was a significant predictor of outcome; (3) showing that the CNS had higher correlation coefficients with the initial neurologic examination than the Glasgow Coma Scale; and (4) assessing the responsiveness of the scale to change in the neurologic status of stroke patients. Interobserver reliability, measured by kappa statistics on each scale item, was good. Accordingly, we established the validity and reliability of the CNS for its use in clinical studies and in the care of stroke patients.

Multiple sclerosis and antecedent infections: a case-control study.

OBJECTIVES: To determine whether there is an excess of respiratory tract infections in the 5-week, 3-month, and 12-month periods before MS symptom onset and if there is an association between MS and a history of infectious mononucleosis (IM). BACKGROUND: The etiology of MS remains unknown, but infection is frequently suggested as a putative etiologic agent. Epidemiologic studies have produced inconsistent evidence for an etiologic role of respiratory tract infections (RTI) and IM in MS. METHODS: The authors performed a case-control study using the General Practice Research Database from the United Kingdom. There were 225 subjects with definite or probable MS, and 900 controls matched for age, sex, and physician practice. Using computerized patient records, the authors compared the mean rates of RTI per patient in the 5-week, 3-month, and 12-month periods before the date of onset of the first symptoms compatible with MS (index date). They also compared histories of IM. RESULTS: In all periods, an increased frequency of RTI was associated with a significantly increased risk of MS. A history of IM was associated with greater than five times the risk of MS (OR = 5.5 [95% CI 1.5 to 19.7]). CONCLUSIONS: These results support an association between a history of IM and subsequent MS. Respiratory tract infections may precipitate disease onset.

Progression of impairment in patients with vascular cognitive impairment without dementia.

Little is known about progression, short of dementia, in vascular cognitive impairment. In the Canadian Study of Health and Aging, 149 participants (79.3 +/- 6.7 years; 61% women) were found to have vascular cognitive impairment, no dementia (CIND). After 5 years, 77 participants (52%) had died and 58 (46%) had developed dementia. Women were at greater risk of dementia (OR 2.1, 1.0 to 4.5). Of 32 participants alive without dementia, cognition had deteriorated in seven and improved in four. Half of those with vascular CIND developed dementia within 5 years, suggesting a target for preventive interventions.

Technetium-99m red blood cell venography in patients with clinically suspected deep vein thrombosis: a prospective study.

We have compared technetium-99m (99mTc) red blood cell (RBC) venography to serial impedance plethysmography (IPG) in 110 consecutive patients with a first episode of clinically suspected deep vein thrombosis (DVT). IPG was performed at Day 0 and, if abnormal, contrast venography was also performed to rule out a falsely positive result. Patients with an initially normal IPG had the test repeated at Days 1, 3, 5 to 7, and 10 to 14. Contrast venography was not performed and anticoagulant treatment was withheld in all patients who remained normal during repeated IPG testing. Technetium-99m RBC venography was performed at Day 0 in patients with an initially abnormal IPG and during the period of serial IPG testing in those with an initially normal IPG. The sensitivity of [99mTc]RBC venography for proximal DVT was 0.68, with 95% confidence limits (CL) from 0.48 to 0.89. Specificity was 0.88 (95% CL from 0.81 to 0.95). When the findings of [99mTc]RBC venography for the entire lower extremity were compared to the reference method, the sensitivity increased to 0.90 (95% CL from 0.82 to 0.97) but the specificity decreased to 0.56 (95% CL from 0.51 to 0.62). Technetium-99m RBC venography is a sensitive but less specific method for detecting DVT of the entire lower extremity. An abnormal [99mTc]RBC venogram, particularly in the calf region, should always be confirmed by another diagnostic method.

Do patient factors alter the relationship between physician characteristics and use of long-acting benzodiazepines?

Despite known hazards associated with their use, long-acting benzodiazepines are frequently used in the treatment of older adults. While such use has been linked to physician characteristics, the effect of patient factors has not been considered. To investigate this, data from 1423 Quebec community-dwelling subjects of the Canadian Study of Health and Aging were linked to records of prescriptions billed to the provincial health insurance program during the year following study entry. The standardized one-year period prevalence of any use of long-acting benzodiazepines was 12.2%. Among benzodiazepine users, long-acting benzodiazepine use was more common among male patients and patients of earlier graduating prescribers and specialist prescribers. However, the effect of the latter two factors were modified by patient self-reported anxiety. This study demonstrates that consideration of patient factors may be necessary to obtain an accurate estimate of the association between at least some physician factors and use of long-acting benzodiazepines.

Undetected dementia in community-dwelling older people: the Canadian Study of Health and Aging.

OBJECTIVE: To estimate the frequency and correlates of undetected dementia in community-dwelling older people. DESIGN: Secondary analysis of data from the Canadian Study of Health and Aging (CSHA) prevalence survey of dementia. SETTING: All 10 provinces of Canada excluding Indian reserves and military units. PARTICIPANTS: A total of 252 community-dwelling older adults diagnosed with dementia in the CSHA survey. MAIN OUTCOME MEASURE: Undetected dementia, defined as occurring in persons who meet standard diagnostic criteria for dementia but who report never having seen a doctor for memory problems. RESULTS: Of the 252 subjects, 64% had undetected dementia. Subjects with mild functional impairment were significantly more likely to have undetected dementia (odds ratio = 2.4, 95% confidence interval 1.2, 5.0). Older subjects and those with mild cognitive impairment showed a trend toward undetected dementia, although the results did not achieve statistical significance. Educational level, number of comorbid conditions, and degree of social support were not significantly associated with undetected dementia. CONCLUSIONS: A large number of older persons are living in the community with undetected dementia. These older people may be at significant risk for delirium, motor vehicle accidents, medication errors, and financial difficulties. As preventive strategies are developed and new cognitive enhancing therapies emerge, we need to reexamine our current guidelines about screening for cognitive impairment in older adults.

Long-term continuous use of benzodiazepines by older adults in Quebec: prevalence, incidence and risk factors.

OBJECTIVE: To determine the prevalence and incidence of long-term use of benzodiazepines and to assess patient-, prescriber-, and drug-related risk factors. DESIGN: Cohort study. PARTICIPANTS: 1,423 community-dwelling older adults in Quebec who participated in the Canadian Study of Health and Aging (CSHA1). MEASUREMENTS: Patient characteristics were obtained from the CSHA1 database. These were linked to provincial health insurance data to ascertain benzodiazepine use and prescriber characteristics. MAIN OUTCOME MEASURE: Use of benzodiazepines for at least 135 of the first 180 days following initiation of use. RESULTS: Twelve-month prevalence of long-term continuous use, standardized by age and gender to the Quebec population, was 19.8%. Twelve-month cumulative incidence of long-term continuous use was 1.9%. Older patients were more likely to proceed to long-term continuous use. CONCLUSIONS: Risk of long-term continuous use of benzodiazepines seems to increase with age. This association was found to be independent of gender, health status, anxiety, cognitive status, benzodiazepine type, and physician characteristics.

Predictors of five-year mortality in older Canadians: the Canadian Study of Health and Aging.

OBJECTIVE: Based on the Canadian Study of Health and Aging (CSHA), to determine the importance of cognitive status, sociodemographic factors, functional status, and other health related factors as predictors of 5-year overall mortality in older Canadians. DESIGN, SETTING AND PARTICIPANTS: Two partially overlapping groups from the Canadian Study of Health and Aging (1991) were identified: (1) older people living in the community (n = 8949) who had a screening interview (larger sample, fewer variables) and (2) older people who underwent an extensive clinical examination (smaller sample, more objective variables; n = 2914). Deaths in the subsequent 5 years were determined from death certificates and interviews with the caregivers. Multivariate logistic regression models, with death within 5 years as the outcome, were developed separately for men and women. Predictor variables were introduced in the following groups: sociodemographic factors, physical and cognitive status, and physical illnesses and life style factors. Parallel models were developed for the screening sample and for the clinical sample. RESULTS AND DISCUSSION: Five-year mortality ranged from 10.0% (women aged 65-74 living in the community) to 88.1% (men aged 85 and older living in institutions). Multivariate models showed that the odds of death within 5 years increased with age. This effect remained after adjustment for all other variables. Odds of death increased with institutionalization and with increasing cognitive and physical impairment. Although vision and hearing problems and the presence of heart disease, stroke, and diabetes were all strongly related to 5-year mortality in univariate, unadjusted analyses, their contributions were minimal in the multivariate analyses. Increased Body Mass Index was associated with lower mortality in both univariate and multivariate analyses. CONCLUSIONS: This population-based study supported the importance of gender, age, functional status, cognition, and health status in predicting 5-year mortality, and after accounting for cognitive status, physical status, and specific disease variables, the difference in mortality between older people in the community and in institutions was reduced. Knowledge about survival and prognosis is important not only for the planning of long-term facilities and home care, but it can also be helpful for clinical decision-making and for family and caregivers.

HM-PAO (CERETEC) SPECT brain scanning in the diagnosis of Alzheimer's disease.

OBJECTIVE: To evaluate the accuracy of Single Photon Emission Computed Tomography (SPECT) scanning in the diagnosis of Alzheimer's Disease (AD) and its capacity to improve the diagnostic accuracy of conventional clinical evaluation. DESIGN: Comparison of SPECT scanning of AD and normal subjects with the criterion standard of clinical diagnosis confirmed by 1-year repeated evaluation. SETTING: A memory clinic in a tertiary care university hospital. PATIENTS: One hundred twenty patients were evaluated upon entering the Jewish General Hospital (McGill University) Memory Clinic. Fifty-eight patients were diagnosed as having AD and 17 as having vascular dementia. Twenty unmatched controls (recruited mainly through newspaper advertisements) were normal, and 25 had cognitive impairment without dementia (not included in the statistical analysis). MAIN OUTCOME MEASURES: Comparison of visual inspection of SPECT, based on the system of classification developed by Holman et al., using B pattern alone as positive or B (bilateral posterior temporal and/or parietal cortex deficits) or C (bilateral posterior temporal and/or parietal deficits with additional defects) pattern and B or C or D (unilateral posterior temporal and/or parietal defects with or without additional defects) as positive compared with clinical diagnosis after repeated evaluations. Sensitivity and specificity, as well as positive predictive value (PPV) and negative predictive value (NPV) based on the prevalence of AD in a memory clinic setting of 30% or 50%, were calculated. RESULTS: With B pattern as positive, the sensitivity of SPECT was 21% whereas the specificity was 80%. With B or C as positive, the sensitivity was 29% and the specificity was 75%. With B or C or D as positive, the sensitivity was 55% and the specificity was 65%. With a 30% prevalence, the PPV with B pattern as positive was 31% whereas the NPV was 30%. The PPV with B or C as positive was 33% while the NPV was 29%, and the PPV with B or C or D as positive was 40% whereas the NPV was 23%. With a 50% prevalence, the PPV with B pattern as positive was 51% and the NPV 49.6%; the PPV with B or C as positive was 54% and the NPV 48.6%; the PPV with B or C or D as positive was 61% while NPV was 41%. CONCLUSION: The sensitivity and specificity were too low for SPECT to be useful as a diagnostic test for AD. The poor positive and negative predictive values in our tertiary care clinic mean that SPECT is not useful in "ruling-in" or "ruling-out" AD in that setting. In fact, clinical evaluation is more accurate.

Agreement between older subjects and proxy informants on history of surgery and childbirth.

OBJECTIVES: To assess the agreement between proxy informants' reports of history of surgery and childbirth and older index subjects' own recall. DESIGN: Interrater reliability study. SETTING: An outpatient family medicine clinic and a provincial electoral district in Montreal, Canada. PARTICIPANTS: Eighty-two subjects aged 65 years and older without cognitive impairment, identified from clinic and community settings, and each index subject's proxy respondent. MEASUREMENTS: Identical questionnaires were administered to index subjects and proxies. RESULTS: Proxies failed to report 39% of non-childbirth surgeries reported by index subjects, but failed to report only 10% of childbirths. Female proxies were significantly less likely than male proxies to underreport non-childbirth surgeries after controlling for age of index subject and interval since surgery. Longer interval since surgery was significantly associated with greater underreporting, whereas age of the index subject and relationship between proxy and index subject were not. Agreement between proxies and index subjects on date of surgery was much higher for childbirths than for non-childbirth surgeries. CONCLUSIONS: Our findings suggest that proxy respondents can provide reliable information on older women's history of childbirth but that use of proxy respondents for history of non-childbirth surgeries may result in substantial underreporting.