Torgeir Engstad

Vascular Factors and Risk of Dementia: Design of the Three-City Study and Baseline Characteristics of the Study Population

Objective: To describe the baseline characteristics of the participants in the Three-City (3C) Study, a study aiming to evaluate the risk of dementia and cognitive impairment attributable to vascular factors. Methods: Between 1999 and 2001, 9,693 persons aged 65 years and over, noninstitutionalized, were recruited from the electoral rolls of three French cities, i.e. Bordeaux, Dijon and Montpellier. Health-related data were collected during face-to-face interviews using standardized questionnaires. The baseline examination included cognitive testing and diagnosis of dementia, and assessment of vascular risk factors, including blood pressure measurements, ultrasound examination of the carotid arteries, and measurement of biological parameters (glycemia, total, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinemia); 3,442 magnetic resonance imaging (MRI) examinations were performed in subjects aged 65–79. Measurements of ultrasound, blood, and MRI parameters were centralized. Two follow-up examinations (at 2 and 4 years) were planned. Results: After exclusion of the participants who had subsequently refused the medical interview, the 3C Study sample consisted of 3,649 men (39.3%) and 5,645 women, mean age 74.4 years, with a relatively high level of education and income. Forty-two percent of the participants reported to be followed up for hypertension, about one third for hypercholesterolemia, and 8% for diabetes; 65% had elevated blood pressure measures (systolic blood pressure ≧140 or diastolic blood pressure ≧90). The proportion of Mini-Mental State Examination scores below 24 was 7% and dementia was diagnosed in 2.2% of the participants. Conclusion: Distribution of baseline characteristics of the 3C Study participants suggests that this study will provide a unique opportunity to estimate the risk of dementia attributable to vascular factors.

Validity of Self-Reported Stroke The Tromsø Study

BACKGROUND AND PURPOSE The aim of this study was to validate the diagnosis of self-reported stroke. METHODS During 1994-1995, 27 159 people attended a population health survey in the community of Tromso, Norway, a response rate of 77%. A total of 418 attenders reported a history of stroke. In 1997, all individuals with a self-reported stroke who were still living in the community (n=362) were invited to a clinical reexamination. For each of the 269 people who were reexamined, a person who reported no history of stroke was selected and was reexamined in the same way. RESULTS On the basis of the reexamination, 213 (79.2%) of the self-reported strokes were confirmed. Thirteen individuals (4.8%) had a possible stroke. The remaining 43 individuals had either transient ischemic attack (TIA; n=18), traumatic head injuries (n=16), or perinatal cerebral damage, complicated migraine, syncope, possible TIA, or cerebral aneurysm without bleeding (n=9). Among the confirmed strokes, 30 (14.1%) were hemorrhagic and 118 (55.4%) were thromboembolic. Of the 30 hemorrhages, 16 were subarachnoidal bleedings, 10 due to ruptured aneurysms. The histories of stroke, including both the symptoms and the signs, often had a paucity of details and precision, making it impossible to classify 65 stroke victims (30.5%) into stroke subtypes. The positive predictive value (PPV) of a self-reported stroke was 0.79. The PPV was significantly (P=0.016) greater in men (0.88) than in women (0.73). Individuals older than 60 years had a significantly greater PPV than those younger than 60 years (PPV 0.83 and 0.73, respectively; P=0.05). Hypertension was associated with a greater PPV, whereas a history of either ischemic heart disease, diabetes mellitus, lung disease, or depression had no impact on the PPV. The estimated sensitivity of self-reported stroke in the survey population was approximately 80% and the specificity was 99%. CONCLUSIONS We conclude that a self-administered questionnaire can be used to assess the prevalence of stroke in epidemiological research.

Bone Mineral Density in Acute Stroke Patients Low Bone Mineral Density May Predict First Stroke in Women

Background and Purpose— Osteoporosis and stroke share several risk factors, including age, smoking, low physical activity, and hypertension. Thus, low bone mineral density (BMD) and high stroke risk may be related. We examined the relationship between BMD and acute stroke in noninstitutionalized men and women aged ≥60 years. Methods— Sixty-three stroke patients (33 women and 30 men) and 188 control subjects from the general population were included. BMD was measured by using dual-energy x-ray absorptiometry at both proximal femurs. The measurements of the stroke patients were performed 6 days after the onset of stroke. Results— The BMD at the femoral neck in the female stroke patients was 8% lower than in the control subjects (P =0.007). In men, no difference in BMD between the stroke patients and their controls was found. Women with BMD values in the lowest quartile had a higher risk of stroke than women with BMD values in the highest quartile (OR 4.8), and the probability value for linear trend over the quartiles was statistically significant (P =0.003). The OR for stroke increased 1.9 per SD (0.13 g/cm2) reduction in BMD, and the association between low BMD and stroke in women remained significant when the analysis was adjusted for potential confounders. Conclusions— Female, but not male, stroke patients have lower BMD than population controls. Low BMD may predict stroke in women.

Co-morbidity and drug treatment in Alzheimer's disease. A cross sectional study of participants in the Dementia Study in Northern Norway

BackgroundInappropriate medical treatment of co-morbidities in Alzheimers disease (AD) is an increasing concern in geriatric medicine. The objective of this study was to compare current drug use related to co-morbidity between individuals with a recent diagnosis of AD and a cognitively healthy control group in a population based clinical trial in Northern Norway.MethodsSetting: Nine rural municipalities with 70 000 inhabitants in Northern Norway.Participants: Participants with and without AD recruited in general practice and by population based screening.187 participants with a recent diagnosis of AD were recruited among community dwellers. Of 791 respondents without cognitive symptoms, 500 were randomly selected and invited to further clinical and cognitive testing. The final control group consisted of 200 cognitively healthy individuals from the same municipalities. Demographic characteristics, data on medical history and current medication were included, and a physical and cognitive examination was performed. The statistical analyses were carried out by independent sample t-test, chi-square, ANCOVA and logistic regression.ResultsA co-morbidity score was significantly higher in AD participants compared to controls. The mean number of drugs was higher for AD participants compared to controls (5.1 ± 3.6 and 2.9 ± 2.4 respectively, p < 0.001 age and gender adjusted), also when adjusted for co-morbidity. AD participants used significantly more anticholinergic, sedative and antidepressant drugs. For nursing home residents with AD the mean number of drugs was significantly higher compared to AD participants living at home (6.9 ± 3.9 and 4.5 ± 3.3, respectively, p < 0.001).ConclusionsAD participants were treated with a significantly higher number of drugs as compared to cognitively healthy controls, even after adjustment for co-morbidity. An inappropriate use of anticholinergic and sedative drugs was identified, especially among nursing home residents with AD. The drug burden and the increased risk of adverse reactions among individuals suffering from AD need more attention from prescribing doctors.

Recruitment methods in Alzheimer's disease research: general practice versus population based screening by mail

BackgroundIn Alzheimers disease (AD) research patients are usually recruited from clinical practice, memory clinics or nursing homes. Lack of standardised inclusion and diagnostic criteria is a major concern in current AD studies. The aim of the study was to explore whether patient characteristics differ between study samples recruited from general practice and from a population based screening by mail within the same geographic areas in rural Northern Norway.MethodsAn interventional study in nine municipalities with 70000 inhabitants was designed. Patients were recruited from general practice or by population based screening of cognitive function by mail. We sent a questionnaire to 11807 individuals ≥ 65 years of age of whom 3767 responded. Among these, 438 individuals whose answers raised a suspicion of cognitive impairment were invited to an extended cognitive and clinical examination. Descriptive statistics, chi-square, independent sample t-test and analyses of covariance adjusted for possible confounders were used.ResultsThe final study samples included 100 patients recruited by screening and 87 from general practice. Screening through mail recruited younger and more self-reliant male patients with a higher MMSE sum score, whereas older women with more severe cognitive impairment were recruited from general practice. Adjustment for age did not alter the statistically significant differences of cognitive function, self-reliance and gender distribution between patients recruited by screening and from general practice.ConclusionsDifferent recruitment procedures of individuals with cognitive impairment provided study samples with different demographic characteristics. Initial cognitive screening by mail, preceding extended cognitive testing and clinical examination may be a suitable recruitment strategy in studies of early stage AD.Clinical RegistrationClinicalTrial.gov Identifier: NCT00443014

Predictors of Death Among Long-Term Stroke Survivors

Background and Purpose— We evaluated the risk factors for death among long-term stroke survivors compared with stroke-free subjects. Methods— In 1997 we investigated 221 stroke survivors (mean, 9.4 years after index stroke) and 243 stroke-free subjects; both groups were recruited from a population-based health study. During the subsequent 5 years, all deaths (51 and 21 in the stroke and stroke-free groups, respectively) were registered. Results— The age- and sex-adjusted total mortality rate for the 5-year follow-up was 21.0% in the stroke group and 7.9% in the stroke-free group (P <0.0001), depending on different rates of cardiovascular deaths (P <0.0001). Better physical and social functioning (P <0.0001) and moderate use of alcohol (P ≤0.004), the latter compared with no use, decreased risk of death, irrespective of stroke status. A myocardial infarction risk score had no impact on death in the stroke group, in contrast to the increased risk seen among the stroke-free group (P =0.0001). Conclusions— The long-term stroke survivors had significant excess risk of death compared with stroke-free subjects. Better physical and social functioning and moderate use of alcohol were associated with decreased risk, whereas a myocardial infarction risk score increased risk for death only in the stroke-free group.

Impaired Motor Speed, Visuospatial Episodic Memory and Verbal Fluency Characterize Cognition in Long-Term Stroke Survivors: The Tromsø Study

The cognitive function after stroke is examined in acute and subacute phase, but poorly characterized in long-term stroke survivors. This paper discusses cognitive function among long-term stroke survivors, with matched stroke-free subjects, based on a population survey. General cognition, verbal, executive and visuospatial function, memory, attention, and motor speed were tested as well as motor function in upper extremities. Stroke survivors and controls were most effectively discriminated by means of motor speed, followed by visuospatial episodic memory and verbal fluency. This pattern of cognitive disturbances may be a consequence of cerebral lesions in frontal subcortical areas, and is different from Alzheimer’s disease.

A Long-Term Follow-Up Programme for Maintenance of Motor Function after Stroke: Protocol of the life after Stroke—The LAST Study

Background. There are no evidence-based strategies that have been shown to be superior in maintaining motor function for months to years after the stroke. The LAST study therefore intends to assess the effect of a long-term follow-up program for stroke patients compared to standard care on function, disability and health. Design. This is a prospective, multi-site randomised controlled trial, with blinded assessment 18 months after inclusion. A total of 390 patients will be recruited and randomised to a control group, receiving usual care, or to an intervention group 10 to 16 weeks after onset of stroke. Patients will be stratified according to stroke severity, age above 80, and recruitment site. The intervention group will receive monthly coaching on physical activity by a physiotherapist for 18 consecutive months after inclusion. Outcomes. The primary outcome is motor function (Motor Assessment Scale) 18 months after inclusion. Secondary outcomes are: dependency, balance, endurance, health-related quality of life, fatigue, anxiety and depression, cognitive function, burden on caregivers, and health costs. Adverse events and compliance to the intervention will be registered consecutively during follow-up.

The effect of stimulation therapy and donepezil on cognitive function in Alzheimer's disease. A community based RCT with a two-by-two factorial design.

BackgroundProgressive neurodegeneration in Alzheimer’s disease (AD) induces cognitive deterioration, and there is controversy regarding the optimal treatment strategy in early AD. Stimulation therapy, including physical exercise and cholinesterase inhibitors are both reported to postpone cognitive deterioration in separate studies. We aimed to study the effect of stimulation therapy and the additional effect of donepezil on cognitive function in early AD.MethodDesign: A two-by-two factorial trial comprising stimulation therapy for one year compared to standard care to which a randomized double-blinded placebo controlled trial with donepezil was added.Setting: Nine rural municipalities in Northern Norway.Participants: 187 participants 65 years and older with a recent diagnosis of mild or moderate AD were included in the study of which 146 completed a one-year follow-up. INTERVENTIONS: In five municipalities the participants received stimulation therapy whereas participants in four received standard care. All participants were randomised double-blindly to donepezil or placebo and tested with three different cognitive tests four times during the one-year study period.Main outcome: Changes in MMSE sum score.Secondary outcome: Changes in ADAS-Cog and Clock Drawing Test.ResultsMMSE scores remained unchanged amongst AD participants receiving stimulation therapy and those receiving standard care. The results were consistent for ADAS-Cog and Clock Drawing Test. No time trend differences were found during one-year follow-up between groups receiving stimulation therapy versus standard care or between donepezil versus placebo.ConclusionIn rural AD patients non-pharmacological and pharmacological therapy did not improve outcome compared with standard care but all groups retained cognitive function during one year follow-up. Other studies are needed to confirm these results.Trial registrationClinicalTrials.gov (Identifier: NCT00443014). EudraCT database (no 2004-002613-37).