Regional variation in primary care improvement strategies and policy: case studies that consider qualitative contextual data for performance measurement in three Canadian provinces.

OBJECTIVE: To explore regional primary care improvement strategies that are potentially determinants of primary care performance. DESIGN: Multiple comparative embedded case study. SETTING: Three regions in Canada: Fraser East, British Columbia; Eastern Ontario Health Unit, Ontario; Central Zone, Nova Scotia. DATA SOURCES: (1) In-depth interviews with purposively selected key informants (eg, primary care decision-makers, physician leads, regulatory agencies) and focus groups with patients and clinicians (n=68 participants) and (2) published and grey literature (n=205 documents). OUTCOME MEASURES: Variations in spread and uptake of primary care improvement strategies across the three study regions. NVivo (V.11) was used to manage data and perform content analysis to identify categories within and across cases. The coding structure was developed by researchers through iterative collaboration, using inductive and deductive processes. RESULTS: Six overarching primary care improvement strategies, differing in focus and spread, were implemented across the three study regions: interprofessional team-based approaches, provider skill mix expansion, physician groups and networks, information systems, remuneration and performance measurement and reporting infrastructure. CONCLUSION: The addition of information on regional improvement strategies to primary care performance reports could add important contextual insights into primary care performance results. This could help identify possible drivers of reported performance outcomes and levers for change in practice, regional and system-level settings.

Derivation and Initial Validation of Clinical Phenotypes of Children Presenting with Concussion Acutely in the Emergency Department: Latent Class Analysis of a Multi-Center, Prospective Cohort, Observational Study.

The identification of clinical phenotypes may help parse the substantial heterogeneity that characterizes children with concussion. This study used latent class analysis (LCA) to identify discernible phenotypes among children with acute concussion and examine the association between phenotypes and persistent post-concussive symptoms (PPCS) at 4 and 12 weeks post-injury. We conducted LCA of variables representing pre-injury history, clinical presentation, and parent symptom ratings, derived from a prospective cohort, observational study that recruited participants from August 2013 until June 2015 at nine pediatric emergency departments within the Pediatric Emergency Research Canada network. This substudy included 2323 children from the original cohort ages 8.00-17.99 years who had data for at least 80% of all variables included in each LCA. Concussion was defined according to Zurich consensus statement diagnostic criteria. The primary outcome was PPCS at 4 and 12 weeks after enrollment. Participants were 39.5% female and had a mean age of 12.8 years (standard deviation = 2.6). Follow-up was completed by 1980 (85%) at 4 weeks and 1744 (75%) at 12 weeks. LCA identified four groups with discrete pre-injury histories, four groups with discrete clinical presentations, and seven groups with discrete profiles of acute symptoms. Clinical phenotypes based on the profile of group membership across the three LCAs varied significantly in their predicted probability of PPCS at 4 and 12 weeks. The results indicate that children with concussion can be grouped into distinct clinical phenotypes, based on pre-injury history, clinical presentation, and acute symptoms, with markedly different risks of PPCS. With further validation, clinical phenotypes may provide a useful heuristic for clinical assessment and management.

Can a customer relationship management program improve recruitment for primary care research studies?

BACKGROUND: Recruiting family physicians into primary care research studies requires researchers to continually manage information coming in, going out, and coming in again. In many research groups, Microsoft Excel and Access are the usual data management tools, but they are very basic and do not support any automation, linking, or reminder systems to manage and integrate recruitment information and processes. OBJECTIVE: We explored whether a commercial customer relationship management (CRM) software program - designed for sales people in businesses to improve customer relations and communications - could be used to make the research recruitment system faster, more effective, and more efficient. FINDINGS: We found that while there was potential for long-term studies, it simply did not adapt effectively enough for our shorter study and recruitment budget. The amount of training required to master the software and our need for ongoing flexible and timely support were greater than the benefit of using CRM software for our study.

Annual Trends in Follow-Up Visits for Pediatric Concussion in Emergency Departments and Physicians' Offices.

OBJECTIVE: To assess whether children and youth with concussion receive follow-up visits in accordance with the recommended guidelines. STUDY DESIGN: We conducted a retrospective, population-based study using linked health administrative data from all concussion-related visits to emergency department and physician offices by children aged 5 through 18 years (range, 5.00-18.99) in Ontario between 2003 and 2013. We analyzed the percentage of children and youth seen for follow-up. The Mann-Kendall test for trends was used to assess a monotonic increasing trend over time in concussion follow-up visits. RESULTS: A total of 126 654 children and youth were evaluated for an index concussion visit. The number of children and youth assessed for concussion follow-up (N = 45 155) has increased significantly over time (P < .001). In 2003, 781 of 7126 patients (11.0%; 95% CI, 10.3-11.7) with an index visit for concussion had a follow-up assessment. By 2013, 6526 of 21 681 (30.1%; 95% CI, 29.5-30.7) patients received follow-up care. CONCLUSIONS: The proportion of children and youth receiving follow-up after an acute concussion has significantly increased between 2003 and 2013. Nevertheless, more than two-thirds of all patients do not seek medical follow-up or clearance as recommended by current concussion guidelines, suggesting that ongoing efforts to improve and monitor compliance with recommended guidelines by patients and physicians are important.

Do Lacunar Infarcts Have Different Aetiologies? Risk Factor Profiles of Lacunar Infarcts in Deep White Matter and Basal Ganglia: The Second Manifestations of ARTerial Disease-Magnetic Resonance Study.

BACKGROUND: Evidence suggests that lacunar infarcts have different etiologies, possibly related to their anatomical location and vascular territory. We investigated the risk factor profiles of patients with new lacunar infarcts in the basal ganglia and deep white matter. METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study, a prospective cohort on brain changes on MRI in patients with symptomatic atherosclerotic disease, 679 patients (57 ± 9 years) had vascular screening and MRI at baseline and after a mean follow-up of 3.9 years. We investigated the association between vascular risk factors at baseline and appearance of new lacunar infarcts in the basal ganglia and deep white matter at follow-up. RESULTS: New lacunar infarcts appeared in 44 patients in the basal ganglia and in 37 patients in the deep white matter. In multivariable analysis, older age, history of cerebrovascular disease, and baseline white matter hyperintensity (WMH) volume were associated with increased risk of new lacunar infarcts in both locations. Hyperhomocysteinemia was associated with increased risk of lacunar infarcts in the basal ganglia (relative risk [RR] 2.0; 95% CI 1.0-4.2), whereas carotid stenosis >70% (RR 2.5; 95% CI 1.2-5.0), smoking (per 10 pack-year: RR 1.1; 95% CI 1.0-1.3), hypertension (RR 3.4; 95% CI 1.2-9.7), and progression of WMH volume (RR 2.4; 95% CI 1.1-5.2) were associated with increased risk of lacunar infarcts in the deep white matter. CONCLUSIONS: The different risk factor profiles for new lacunar infarcts in basal ganglia and deep white matter indicate different etiologies. The independent association between progression of WMH and new deep white matter lacunar infarcts suggest a common etiology for these radiological abnormalities.

Annual and Seasonal Trends in Ambulatory Visits for Pediatric Concussion in Ontario between 2003 and 2013.

OBJECTIVE: To investigate annual and seasonal trends in physician office and emergency department (ED) visit rates for pediatric concussion in Ontario between 2003 and 2013. STUDY DESIGN: A retrospective, population-based study was conducted using linked health administrative data from all concussion-related visits to ED and physician office by children aged 5 through 18 years. Time series analysis was used to assess whether periodic components exist in the monthly number of concussion-related visits. RESULTS: Over the 11-year study period, there were 176 685 pediatric visits for concussion in EDs and physician offices in Ontario. Standardized concussion-related visits showed a 4.4-fold (95% CI 4.37-4.45) increase per 100 000 from 2003 to 2013, with nearly 35 000 total visits in 2013. Concussion-related visits demonstrated a steep increase from 2010 onward. The greatest increases in standardized visits were in females (6.3-fold, 95% CI 6.23-6.46 vs 3.6-fold, 95% CI 3.56-3.64 in males) and 13-18.99 year olds (5.0-fold, 95% CI 4.93-5.08 vs 4.1-fold, 95% CI 3.99-4.27 in 9-12 years and 2.3-fold, 95% CI 2.23-2.42 in 5-8 years). A strong seasonal variability (R2autoreg = 0.87, P < .01) in the number of concussion-related visits was present, with most occurring in fall and winter. CONCLUSIONS: Pediatric concussion-related ED and physician office visit rates have greatly increased in the last decade, particularly since 2010. Prevention strategies may be targeted at those most at risk and at seasonal-related activities carrying the greatest risk of concussion.

Association Between Early Participation in Physical Activity Following Acute Concussion and Persistent Postconcussive Symptoms in Children and Adolescents.

Importance: Although concussion treatment guidelines advocate rest in the immediate postinjury period until symptoms resolve, no clear evidence has determined that avoiding physical activity expedites recovery. Objective: To investigate the association between participation in physical activity within 7 days postinjury and incidence of persistent postconcussive symptoms (PPCS). Design, Setting, and Participants: Prospective, multicenter cohort study (August 2013-June 2015) of 3063 children and adolescents aged 5.00-17.99 years with acute concussion from 9 Pediatric Emergency Research Canada network emergency departments (EDs). Exposures: Early physical activity participation within 7 days postinjury. Main Outcomes and Measures: Physical activity participation and postconcussive symptom severity were rated using standardized questionnaires in the ED and at days 7 and 28 postinjury. PPCS (≥3 new or worsening symptoms on the Post-Concussion Symptom Inventory) was assessed at 28 days postenrollment. Early physical activity and PPCS relationships were examined by unadjusted analysis, 1:1 propensity score matching, and inverse probability of treatment weighting (IPTW). Sensitivity analyses examined patients (≥3 symptoms) at day 7. Results: Among 2413 participants who completed the primary outcome and exposure, (mean [SD] age, 11.77 [3.35] years; 1205 [39.3%] females), PPCS at 28 days occurred in 733 (30.4%); 1677 (69.5%) participated in early physical activity including light aerobic exercise (n = 795 [32.9%]), sport-specific exercise (n = 214 [8.9%]), noncontact drills (n = 143 [5.9%]), full-contact practice (n = 106 [4.4%]), or full competition (n = 419 [17.4%]), whereas 736 (30.5%) had no physical activity. On unadjusted analysis, early physical activity participants had lower risk of PPCS than those with no physical activity (24.6% vs 43.5%; Absolute risk difference [ARD], 18.9% [95% CI,14.7%-23.0%]). Early physical activity was associated with lower PPCS risk on propensity score matching (n = 1108 [28.7% for early physical activity vs 40.1% for no physical activity]; ARD, 11.4% [95% CI, 5.8%-16.9%]) and on inverse probability of treatment weighting analysis (n = 2099; relative risk [RR], 0.74 [95% CI, 0.65-0.84]; ARD, 9.7% [95% CI, 5.7%-13.7%]). Among only patients symptomatic at day 7 (n = 803) compared with those who reported no physical activity (n = 584; PPCS, 52.9%), PPCS rates were lower for participants of light aerobic activity (n = 494 [46.4%]; ARD, 6.5% [95% CI, 5.7%-12.5%]), moderate activity (n = 176 [38.6%]; ARD, 14.3% [95% CI, 5.9%-22.2%]), and full-contact activity (n = 133 [36.1%]; ARD, 16.8% [95% CI, 7.5%-25.5%]). No significant group difference was observed on propensity-matched analysis of this subgroup (n = 776 [47.2% vs 51.5%]; ARD, 4.4% [95% CI, -2.6% to 11.3%]). Conclusions and Relevance: Among participants aged 5 to 18 years with acute concussion, physical activity within 7 days of acute injury compared with no physical activity was associated with reduced risk of PPCS at 28 days. A well-designed randomized clinical trial is needed to determine the benefits of early physical activity following concussion.

The natural course of elevated levels of depressive symptoms in patients with vascular disease over eight years of follow-up. The SMART-Medea study.

BACKGROUND: Patients with cardiovascular disease have an increased risk for depression, and depression predicts poor prognosis in these patients, but the long-term course of depression is not known. We studied the natural course of elevated levels of depressive symptoms in patients with cardiovascular disease over eight years follow-up. METHODS: Within the Second Manifestations of ARTerial disease - Memory, depression and aging (SMART-Medea) study, depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9) in 690 patients (62±10 years) at baseline and bi-annually during 8 years follow-up. Natural course was described for symptom severity and course type (never, single episode, intermittent, and chronic) based on the cut-off point of ≥6 on the PHQ-9. Using multinomial regression analysis (reference: never depressed) we estimated age- and sex-adjusted odds ratios (OR) for the associations of demographic factors and vascular disease categories with course type. RESULTS: Of the 690 patients, 60% was never depressed, 10% had a single episode, 19% had an intermittent and 11% a chronic course of depression. Increased risk for chronic course was observed for women (OR=3.42; 95% CI=1.98-5.90), those with younger age (OR=3.20; 95% CI=1.73-5.94), and for patients with cerebrovascular disease when compared to patients with coronary artery disease (OR=2.50; 95% CI=1.31-4.78). LIMITATIONS: No information was available on clinical diagnosed major depressive disorder and/or clinical events during follow-up. CONCLUSIONS: In patients with cardiovascular disease, an intermittent or chronic course of elevated levels of depressive symptoms is very common. Patients with cardiovascular disease may require more careful clinical monitoring and management of depressive symptoms.

Clinical Risk Score for Persistent Postconcussion Symptoms Among Children With Acute Concussion in the ED.

IMPORTANCE: Approximately one-third of children experiencing acute concussion experience ongoing somatic, cognitive, and psychological or behavioral symptoms, referred to as persistent postconcussion symptoms (PPCS). However, validated and pragmatic tools enabling clinicians to identify patients at risk for PPCS do not exist. OBJECTIVE: To derive and validate a clinical risk score for PPCS among children presenting to the emergency department. DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter cohort study (Predicting and Preventing Postconcussive Problems in Pediatrics [5P]) enrolled young patients (aged 5-<18 years) who presented within 48 hours of an acute head injury at 1 of 9 pediatric emergency departments within the Pediatric Emergency Research Canada (PERC) network from August 2013 through September 2014 (derivation cohort) and from October 2014 through June 2015 (validation cohort). Participants completed follow-up 28 days after the injury. EXPOSURES: All eligible patients had concussions consistent with the Zurich consensus diagnostic criteria. MAIN OUTCOMES AND MEASURES: The primary outcome was PPCS risk score at 28 days, which was defined as 3 or more new or worsening symptoms using the patient-reported Postconcussion Symptom Inventory compared with recalled state of being prior to the injury. RESULTS: In total, 3063 patients (median age, 12.0 years [interquartile range, 9.2-14.6 years]; 1205 [39.3%] girls) were enrolled (n = 2006 in the derivation cohort; n = 1057 in the validation cohort) and 2584 of whom (n = 1701 [85%] in the derivation cohort; n = 883 [84%] in the validation cohort) completed follow-up at 28 days after the injury. Persistent postconcussion symptoms were present in 801 patients (31.0%) (n = 510 [30.0%] in the derivation cohort and n = 291 [33.0%] in the validation cohort). The 12-point PPCS risk score model for the derivation cohort included the variables of female sex, age of 13 years or older, physician-diagnosed migraine history, prior concussion with symptoms lasting longer than 1 week, headache, sensitivity to noise, fatigue, answering questions slowly, and 4 or more errors on the Balance Error Scoring System tandem stance. The area under the curve was 0.71 (95% CI, 0.69-0.74) for the derivation cohort and 0.68 (95% CI, 0.65-0.72) for the validation cohort. CONCLUSIONS AND RELEVANCE: A clinical risk score developed among children presenting to the emergency department with concussion and head injury within the previous 48 hours had modest discrimination to stratify PPCS risk at 28 days. Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility.

Scalp Hematoma Characteristics Associated With Intracranial Injury in Pediatric Minor Head Injury.

OBJECTIVES: Minor head trauma accounts for a significant proportion of pediatric emergency department (ED) visits. In children younger than 24 months, scalp hematomas are thought to be associated with the presence of intracranial injury (ICI). We investigated which scalp hematoma characteristics were associated with increased odds of ICI in children less than 17 years who presented to the ED following minor head injury and whether an underlying linear skull fracture may explain this relationship. METHODS: This was a secondary analysis of 3,866 patients enrolled in the Canadian Assessment of Tomography of Childhood Head Injury (CATCH) study. Information about scalp hematoma presence (yes/no), location (frontal, temporal/parietal, occipital), and size (small and localized, large and boggy) was collected by emergency physicians using a structured data collection form. ICI was defined as the presence of an acute brain lesion on computed tomography. Logistic regression analyses were adjusted for age, sex, dangerous injury mechanism, irritability on examination, suspected open or depressed skull fracture, and clinical signs of basal skull fracture. RESULTS: ICI was present in 159 (4.1%) patients. The presence of a scalp hematoma (n = 1,189) in any location was associated with significantly greater odds of ICI (odds ratio [OR] = 4.4, 95% confidence interval [CI] = 3.06 to 6.02), particularly for those located in temporal/parietal (OR = 6.0, 95% CI = 3.9 to 9.3) and occipital regions (OR = 5.6, 95% CI = 3.5 to 8.9). Both small and localized and large and boggy hematomas were significantly associated with ICI, although larger hematomas conferred larger odds (OR = 9.9, 95% CI = 6.3 to 15.5). Although the presence of a scalp hematoma was associated with greater odds of ICI in all age groups, odds were greatest in children aged 0 to 6 months (OR = 13.5, 95% CI = 1.5 to 119.3). Linear skull fractures were present in 156 (4.0%) patients. Of the 111 patients with scalp hematoma and ICI, 57 (51%) patients had a linear skull fracture and 54 (49%) did not. The association between scalp hematoma and ICI attenuated but remained significant after excluding patients with linear skull fracture (OR = 3.3, 95% CI = 2.1 to 5.1). CONCLUSIONS: Large and boggy and nonfrontal scalp hematomas had the strongest association with the presence of ICI in this large pediatric cohort. Although children 0 to 6 months of age were at highest odds, the presence of a scalp hematoma also independently increased the odds of ICI in older children and adolescents. The presence of a linear skull fracture only partially explained this relation, indicating that ruling out a skull fracture beneath a hematoma does not obviate the risk of intracranial pathology.

Cerebellar infarct patterns: The SMART-Medea study.

OBJECTIVE: Previous studies on cerebellar infarcts have been largely restricted to acute infarcts in patients with clinical symptoms, and cerebellar infarcts have been evaluated with the almost exclusive use of transversal MR images. We aimed to document the occurrence and 3D-imaging patterns of cerebellar infarcts presenting as an incidental finding on MRI. METHODS: We analysed the 1.5 Tesla MRI, including 3D T1-weighted datasets, of 636 patients (mean age 62 ± 9 years, 81% male) from the SMART-Medea study. Cerebellar infarct analyses included an assessment of size, cavitation and gliosis, of grey and white matter involvement, and of infarct topography. RESULTS: One or more cerebellar infarcts (mean 1.97; range 1-11) were detected in 70 out of 636 patients (11%), with a total amount of 138 infarcts identified, 135 of which showed evidence of cavitation. The average mean axial diameter was 7 mm (range 2-54 mm), and 131 infarcts (95%) were smaller than 20 mm. Hundred-thirty-four infarcts (97%) involved the cortex, of which 12 in combination with subcortical white matter. No infarcts were restricted to subcortical branches of white matter. Small cortical infarcts involved the apex of a deep (pattern 1) or shallow fissure (pattern 2), or occurred alongside one (pattern 3) or opposite sides (pattern 4) of a fissure. Most (87%) cerebellar infarcts were situated in the posterior lobe. CONCLUSIONS: Small cerebellar infarcts proved to be much more common than larger infarcts, and preferentially involved the cortex. Small cortical infarcts predominantly involved the posterior lobes, showed sparing of subcortical white matter and occurred in characteristic topographic patterns.

Structural MRI correlates of apathy symptoms in older persons without dementia: AGES-Reykjavik Study.

OBJECTIVE: We aimed to investigate the relation between apathy symptoms and structural brain changes on MRI, including white matter lesions (WMLs) and atrophy, in a large cohort of older persons. METHODS: Cross-sectional analyses are based on 4,354 persons without dementia (aged 76 ± 5 years) participating in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study. Apathy symptoms were assessed with 3 items from the 15-item Geriatric Depression Scale. Brain volumes and total WML volume were estimated on 1.5-tesla MRI using an automated segmentation program; regional WML load was calculated using a semiquantitative scale. Regression analyses were adjusted for age, sex, education, intracranial volume, vascular risk factors, physical activity, brain infarcts, depressive symptoms, antidepressants, and cognitive status. RESULTS: Compared to those with <2 apathy symptoms, participants with ≥ 2 apathy symptoms (49% of the cohort) had significantly smaller gray matter volumes (mean adjusted difference -3.6 mL, 95% confidence interval [CI] -6.2 to -1.0), particularly in the frontal and temporal lobes; smaller white matter volumes (mean adjusted difference -1.9 mL, 95% CI -3.6 to -0.3), mainly in the parietal lobe; and smaller thalamus volumes. They were also more likely to have WMLs in the frontal lobe (adjusted odds ratio = 1.08, 95% CI 0.9-1.3). Excluding participants with a depression diagnosis did not change the associations. CONCLUSIONS: In this older population without dementia, apathy symptoms are associated with a more diffuse loss of both gray and white matter volumes, independent of depression.

Antidepressant use is related to larger white matter lesion volume in patients with symptomatic atherosclerotic disease: the SMART-MR study.

Although a relation between depression and white matter lesions (WML) is frequently observed, the direction of causation remains unknown. We investigated whether depressed mood was associated with baseline severity and change in WML volume during 4 years of follow-up, and the relative contribution of mood symptoms and antidepressant use to this relation. Within the SMART-MR study 594 patients (58 ± 10 years) with symptomatic atherosclerotic disease had assessments of mood symptoms and antidepressant use and 1.5 T MRI at baseline and after 3.9 ± 0.4 years of follow-up. Mood symptoms were assessed using the Mental Health Index (MHI-5). Depressed mood was defined as antidepressant use and/or MHI-5 score ≤ 52. Volumetric WML measures (deep and periventricular) were obtained with automated segmentation. Linear regression analyses were adjusted for age, sex, baseline WML volume, follow-up time, vascular risk factors and infarcts. Depressed mood was not associated with larger WML volume at baseline. However, when separate contributions were distinguished, antidepressant use was associated with greater deep (B = 0.50 mL, 95 % CI 0.04-0.96) and periventricular WML volume (B = 0.47 mL, 95 % CI 0.05-0.89) at baseline, while mood symptoms were not. Antidepressants were associated with a modest but non-significant increase in progression of periventricular WML volume over 4 years of follow-up (B = 0.21 mL, 95 % CI -0.05 to 0.47). WML at baseline were not associated with new-onset depressed mood at follow-up. Antidepressants, but not mood symptoms, were associated with greater WML volume and a modest, although non-significant increase in periventricular WML volume in patients with symptomatic atherosclerotic disease. Future studies are needed to determine whether this may be a direct effect, or whether other underlying diseases for which antidepressants are prescribed influence this relation.

Lacunar infarcts in deep white matter are associated with higher and more fluctuating depressive symptoms during three years follow-up.

BACKGROUND: Disruption of frontal-subcortical circuits by cerebral small-vessel disease is thought to predispose to depression characterized by motivational symptoms. We examined the influence of lacunar infarcts and white matter lesions (WML) on severity and course of depressive symptoms during 3 years follow-up. METHODS: Within the SMART-Medea study, analyses were performed in 650 patients with symptomatic atherosclerotic disease (62±9 years). Volumetric WML measures (deep and periventricular) were obtained with 1.5T magnetic resonance imaging at baseline; infarcts were rated visually. Depressive symptoms were assessed with Patient Health Questionnaire-9 at baseline and during five follow-up times and categorized into motivational and mood scores. RESULTS: Using generalized estimating equation models, a relation between lacunar infarcts in deep white matter and an increased severity (mean difference=1.47, 95% confidence interval .33-2.60) and more fluctuating course (p value interaction infarcts * time=.04) of depressive symptoms during follow-up was found, adjusted for age, sex, education, vascular risk, and cognition. This relation was primarily driven by motivational symptoms. Lacunar infarcts were not associated with severity or course of depressive symptoms. Deep WML were associated with a more fluctuating but not more severe course of depressive symptoms. Excluding patients with major depressive disorder did not change the results. CONCLUSIONS: In patients with symptomatic atherosclerotic disease and relatively mild depressive symptoms, depressive symptoms, characteristic of motivational problems, remained higher during 3 years follow-up in patients with lacunar infarcts in deep white matter and that symptom severity fluctuated over time.

Mood problems increase the risk of mortality in patients with lacunar infarcts: the SMART-MR study.

OBJECTIVE: A relationship between depression and mortality has been well established, but underlying mechanisms remain unclear. We investigated the influence of cerebral small vessel disease (CSVD), characterized by white matter lesions (WMLs) and lacunar infarcts, on the relationship between mood mortality during 6 years follow-up. METHODS: Mood problems were assessed with the mental component summary of the 36-item Short-Form Medical Outcomes Study in 1110 patients with symptomatic atherosclerotic disease (mean age 59 years). Volumetric WML estimates were obtained with 1.5-T magnetic resonance imaging; lacunar infarcts were scored visually. Cox regression models were adjusted for age, sex, vascular risk, physical functioning, antidepressants and infarcts. We adjusted for CSVD to examine whether it may be an intermediate or confounding factor. Second, we added interaction terms to investigate whether associations differed between patients with CSVD (absent/present). RESULTS: Patients in the lowest quartile of mental functioning, representing most severe mood problems, were at higher, although not significant, risk of death (hazard ratio [HR] = 1.47, 95% confidence interval [CI] = 0.94-2.30) compared with patients in higher quartiles. Adjustment for CSVD did not change this association. Lacunar infarcts, not WML, modified the association of mood problems with mortality (p value for interaction = .01); mood problems strongly increased the risk of mortality in patients with lacunar infarcts (HR = 2.75, 95% CI = 1.41-5.38) but not in those without it (HR = 0.78, 95% CI = 0.39-1.57). CONCLUSIONS: Patients with lacunar infarcts may be especially vulnerable for the effect of mood problems on mortality.

Angiotensin-converting enzyme and progression of white matter lesions and brain atrophy--the SMART-MR study.

High levels of angiotensin-converting-enzyme (ACE) may increase the risk of dementia through blood pressure elevation and subsequent development of cerebral small-vessel disease. However, high ACE levels may also decrease this risk through amyloid degradation which prevents brain atrophy. Within the SMART-MR study, a prospective cohort study among patients with symptomatic atherosclerotic disease, serum ACE levels were measured at baseline and a 1.5 Tesla brain MRI was performed at baseline and after on average (range) 3.9 (3.0-5.8) years of follow-up in 682 persons (mean age 58 ± 10 years). Brain segmentation was used to quantify total, deep, and periventricular white matter lesion (WML) volume, and total brain, cortical gray matter and ventricular volume (%ICV). Lacunar infarcts were rated visually. Regression analyses were used to examine the prospective associations between serum ACE and brain measures. Patients with the highest serum ACE levels (>43.3 U/L) had borderline significantly more progression of deep WML volumes than patients with the lowest ACE levels (<21.8 U/L); mean difference (95% CI) in change was 0.20 (-0.02; 0.43) %ICV. On the contrary, patients with the highest serum ACE levels had significantly less progression of cortical brain atrophy than patients with the lowest ACE levels; mean difference (95% CI) in change was 0.78 (0.21; 1.36) %ICV. Serum ACE was not associated with subcortical atrophy, periventricular WML, or lacunar infarcts. Our results show that higher ACE activity is associated with somewhat more progression of deep WML volume, but with less progression of cortical brain atrophy. This suggests both detrimental and beneficial effects of high ACE levels on the brain.

Progression of White Matter Lesion Volume and Health-Related Quality of Life in Patients with Symptomatic Atherosclerotic Disease: The SMART-MR Study.

Objectives. Mechanisms influencing the course of physical and mental functioning after an atherosclerotic event are unclear. We examined effects of white matter lesion (WML) activity on changes in functioning in patients with symptomatic atherosclerotic disease. Methods. In 486 patients (58 ± 9 years) of the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study, volumetric WML measurements on 1.5T MRI were performed at baseline and 3.9 ± 0.4 years followup. Functioning was assessed with the modified Short-Form 12 (SF-12) questionnaire. Associations of WML progression with changes in functioning were adjusted for age, sex, and vascular risk factors. Results. Physical functioning (baseline: 44, 10th-90th percentile 29-55) improved, whereas mental functioning (baseline: 51, 10th-90th percentile 32-60) declined during followup. WML progression (highest quartile versus rest) contributed to a stronger decline in mental functioning (B = -1.76, 95% CI -3.11 to -0.42), but did not influence changes in physical functioning. Conclusions. Progression of WML volume contributes to a decline in mental functioning in patients with symptomatic atherosclerotic disease.

Location of cerebrovascular and degenerative changes, depressive symptoms and cognitive functioning in later life: the SMART-Medea study.

OBJECTIVES: Depression and cognitive impairment are highly prevalent in later life and frequently co-occur. Structural changes in critical brain regions may underlie both conditions. The authors examined associations of infarcts, white-matter lesions (WML) and atrophy at different locations with depressive symptoms and cognitive functioning. METHODS: Within the Second Manifestations of Arterial Disease-Memory, Depression and Aging (SMART-Medea) study, cross-sectional analyses were performed in 585 non-demented patients aged ≥50 years with symptomatic atherosclerotic disease. Volumetric measures of WML and atrophy were obtained with 1.5 T MRI; infarcts were rated visually. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (score ≥6). z Scores of executive functioning, memory and processing speed were calculated. Analyses were adjusted for age, sex, education, intelligence, vascular disease, physical functioning and co-occurring brain changes. RESULTS: Depressive symptoms were present in 102 (17%) patients and were associated with poorer memory (B=-0.26, 95% CI -0.47 to -0.06). Large subcortical infarcts and lacunar infarcts in deep white-matter tracts were both associated with depressive symptoms (RR=2.66, 95% CI 1.28 to 5.54; RR=2.02, 95% CI 1.14 to 3.59) and poorer executive functioning and memory. Periventricular WML volume was associated with poorer executive functioning; cortical infarcts in the left hemisphere and media flow region, ventricular volume and cortical atrophy were associated with a slower processing speed. CONCLUSION: In this sample of non-demented older persons, subcortical infarcts contributed to an increased risk of depressive symptoms as well as cognitive impairment. This depended on location in projecting white-matter tracts, and not on infarct size.