Galectin-3, a marker of cardiac remodeling, is inversely related to serum levels of marine omega-3 fatty acids. A cross-sectional study.

OBJECTIVE: Marine polyunsaturated n-3 fatty acids (n-3 PUFA) may have cardioprotective effects and beneficial influence on the fibrotic process. We evaluated the associations between serum marine n-3 PUFA and selected biomarkers of fibrosis and cardiac remodeling in elderly patients with acute myocardial infarction. SETTING: From the ongoing OMega-3 fatty acids in Elderly patients with Myocardial Infarction (OMEMI) trial, 299 patients were investigated. Soluble ST2 (sST2), Galectin-3 (Gal-3) and the serum content of major marine n-3 and n-6 PUFA were analyzed 2-8 weeks after the index acute myocardial infarction. RESULTS: Gal-3 was inversely correlated to eicosapentaenoic acid (r = -.120, p = .039) and docosahexaenoic acid (r = -.125, p = .031) and positively correlated to the n-6/n-3 ratio (r = .131, p = .023). Gal-3 levels were significantly higher in diabetics vs non-diabetics (12.00 vs 9.61 ng/mL, p = .007) and in patients with NYHA class ≥III for dyspnea at inclusion (11.33 vs 9.75 ng/mL, p = .006). CONCLUSIONS: The associations between the marine n-3 PUFA and levels of Gal-3 indicate beneficial effects of n-3 PUFA on cardiac remodeling in an elderly population with acute myocardial infarction.

Characterization of ATM mutations in 41 Nordic families with ataxia telangiectasia.

The Ataxia Telangiectasia Mutation (ATM) gene is mutated in the rare recessive syndrome Ataxia Telangiectasia (AT), which is characterized by cerebellar degeneration, immunodeficiency, and cancer predisposition. In this study, 41 AT families from Denmark, Finland, Norway, and Sweden were screened for ATM mutations. The protein truncation test (PTT), fragment length and heteroduplex analyses of large (0.8-1.2 kb) cDNA fragments were used. In total, 67 of 82 (82%) of the disease-causing alleles were characterized. Thirty-seven unique mutations were detected of which 25 have not previously been reported. The mutations had five different consequences for the ATM transcript: mutations affecting splicing (43%); frameshift mutations (32%); nonsense mutations (16%); small in-frame deletions (5%); and one double substitution (3%). In 28 of the probands mutations were found in both alleles, in 11 of the probands only one mutated allele was detected, and no mutations were detected in two Finnish probands. One-third of the probands (13) were homozygous, whereas the majority of the probands (26) were compound heterozygote with at least one identified allele. Ten alleles were found more than once; one Norwegian founder mutation constituted 57% of the Norwegian alleles. Several sequence variants were identified, none of them likely to be disease-causing. Some of them even involved partial skipping of exons, leading to subsequent truncation of the ATM protein.

Identical mutation in 55% of the ATM alleles in 11 Norwegian AT families: evidence for a founder effect.

The ATM gene is responsible for the autosomal recessive disorder Ataxia-Telangiectasia (AT). Many different mutations, located all across the gene, have been reported with a predominance of truncating mutations. By using PTT (protein truncation test) a mutation was found in one Norwegian AT family. Sequencing revealed that the mutation affected nucleotides 3245-3247, codon 1082, and changed the sequence from ATC to TGAT, inducing a stop codon downstream at codon 1095 and leading to early truncation of the ATM protein. Perpendicular DGGE (denaturing gradient gel electrophoresis) was used to screen 10 additional families for this mutation. The 3245 delATC insTGAT mutation was found in 12 of 22 proband alleles: five patients were homozygotes and two heterozygotes. Haplotype analyses were performed using eight microsatellite markers, within and flanking the ATM gene. All carriers of the mutation described were found to have a common haplotype of the five closest CA-repeat microsatellite markers. Genealogical investigations of the families identified a common ancestor for three of the families. The common ancestor was a woman born in 1684 in the area from which these families originate. The prevalence of this mutation in Norwegian patients now allows a major subset of AT heterozygotes to be identified, both in the general population and in breast cancer patients, so that their cancer risk can be evaluated.

Prevalence and clinical correlates of psychotic symptoms in Parkinson disease: a community-based study.

BACKGROUND: Hallucinations and delusions are frequent in patients with Parkinson disease (PD) and may have severe clinical consequences for those patients and their caregivers. However, the prevalence and clinical features of these symptoms have not been studied in a representative sample. OBJECTIVE: To study the prevalence and clinical correlates of psychosis in a population-based sample of patients with PD. METHOD: Total ascertainment of patients with PD in a defined geographical area in Norway was attempted through a detailed community study. Clinical evaluation consisted of a neurologic examination and assessments of depression and cognition. Psychosis was assessed with the thought disorder subscale of the Unified Parkinson's Disease Rating Scale. RESULTS: A total of 245 patients with PD were identified, 235 (95.9%) of whom participated in this study. Twenty-three patients (9.8%) had hallucinations with insight retained, and another 14 patients (6.0%) had more severe hallucinations or delusions. Psychotic symptoms were associated with age, stage and diagnostic subgroup of PD, severity of depression, and cognitive impairment. Type, duration, and dose of antiparkinson drug therapy did not differ between those patients with PD who had or did not have psychosis. In a polychotomous logistic regression analysis, severity of depression, cognitive impairment, and impairment of activities of daily living were the only significant concomitants of psychosis. CONCLUSIONS: Hallucinations and delusions are common in patients with PD. More advanced and widespread brain changes seem to increase the risk for developing psychosis in patients with PD receiving levodopa therapy.

Risk factors for depression in Parkinson disease.

OBJECTIVE: To evaluate whether depression in Parkinson disease (PD) is more closely related to the underlying neuropathological process or to environmental and psychological factors by correlating depression in PD with various clinical and demographic variables. DESIGN: Major depression, level of depressive symptoms as measured with the Montgomery-Aasberg Depression Rating Scale (MADRS), and clinical characteristics were investigated in a community-based cross-sectional study of carefully diagnosed patients with PD. Both bivariate and multivariate correlation analyses were performed to investigate correlations and predictive values of possible risk factors for major depression and MADRS score in PD. SETTING: Depression among patients with PD derived from a prevalence study in the county of Rogaland, Norway. PATIENTS: Two hundred forty-five patients with PD. RESULTS: Impaired cognitive function and the presence of a thought disorder were significant predictors of major depression. A Mini-Mental State Examination sum score below 24 and level 2 or higher on the thought disorder subscale of the Unified Parkinson Disease Rating Scale increased the probability of major depression by a factor of 6.6 and 3.5, respectively. Higher MADRS scores were also associated with lower Mini-Mental State Examination score and higher thought disorder score. In addition, MADRS scores also correlated with more impairment in activities of daily living, presence of motor fluctuations, more evidence of atypical parkinsonism, higher daily doses of levodopa, and younger age on the day on which prevalence was determined. CONCLUSIONS: Most of the observations of this study favor the hypothesis that depression in PD is a primary consequence of brain dysfunction. Situational factors may, however, also contribute to mood changes in PD.

A low, 'normal' score on the Mini-Mental State Examination predicts development of dementia after three years.

OBJECTIVES: To study whether a low, "normal" sumscore (i.e., 24 or higher) on the Mini-Mental Status Examination (MMSE) near the cutpoint usually employed for identifying persons with cognitive impairment predicts later development of dementia. DESIGN: A prospective study of a random sample of nondemented persons aged 75 years and older, according to DSM-III criteria, with follow-ups after 3 and 6 years. PARTICIPANTS: The subjects were 215 persons living at home, mean age 81 years, 81% women. Their mean MMSE sumscore at the start of the study (T0) was 27.9 (range 24-30). MAIN RESULTS: A low MMSE sumscore at T0 was identified as a statistically strongly significant predictor of dementia after 3 years (P < .001), when more than 40% of those with a sumscore of 24 or 25 at T0 had become demented. A similar, although weaker and statistically nonsignificant, trend was observed for the risk after 6 years in relation to MMSE scoring at baseline. CONCLUSION: Persons with a sumscore of 24 or 25 and classified as not suffering from dementia according to the DSM-III criteria are at high risk of developing dementia within 3 years.

The Mini-Mental State Examination: identifying the most efficient variables for detecting cognitive impairment in the elderly.

OBJECTIVES: To study how well the scoring on each item of the MMSE relates to the sum-score when the purpose is to identify persons with cognitive impairment, and to identify an equally effective subset of MMSE items for predicting cognitive impairment. DESIGN: Retrospective survey of MMSE data for 850 elderly. SETTING: A variety of clinical settings. PARTICIPANTS: Mean age 82 years (range 54 to 99), 74% women. The subjects were of three different categories: geriatric in-patients, patients living under supervision, and elderly people living independently at home. RESULTS: Five of the binomial ("State," "Town," "Name a pencil," "Name a watch," "Read and obey") and one of the polychotomous MMSE variables ("Learn three words and repeat immediately") had low sensitivity and gave high percentages of misclassifications versus the sumscore dichotomized at the cut-point 23/24. Univariate logistic regression indicated that the three remaining polychotomous variables ("Spell backwards," "Recall three words," and "Three-stage command") can be scored binomially. Two factors were identified on factor analysis. Logistic regression analysis showed that 12 of the original 20 items predicted the sumscore dichotomized at 23/24 with only 3% misclassifications. Validation against the psychogeriatrician's diagnosis showed that this 12-items MMSE derivative performs as well as the full MMSE. CONCLUSIONS: Six of the 20 MMSE variables perform poorly regarding sensitivity and misclassifications versus the sumscore at cut-point 23/24. Two additional items did not contribute to the prediction of a low/high sumscore. The remaining 12 MMSE items can all be scored binomially and produce a sumscore which is equally as effective as the sumscore of the full MMSE when the purpose is to identify elderly patients with cognitive impairment.

Predictors of nursing home placement in Parkinson's disease: a population-based, prospective study.

OBJECTIVES: To examine the rate and predictors of nursing home placement in patients with Parkinson's disease. DESIGN: Four-year prospective study. SETTING: A population-based study in western Norway PARTICIPANTS: 178 community-dwelling subjects with Parkinson's disease. MEASUREMENTS: Main outcome measure was the time from baseline to nursing home admission. Baseline evaluation of motor symptoms (Unified Parkinson's Disease Rating Scale, UPDRS), cognition (clinical dementia interview, Gottfries, Brane & Steen dementia scale, and Mini-Mental State Examination), depression (clinical interview and the Montgomery & Asberg Depression Rating Scale), and psychotic symptoms (UPDRS Thought Disorder item) were performed. RESULTS: Forty-seven patients (26.4%) were admitted to a nursing home during the 4-year study period. Institutionalized patients were older, had more advanced Parkinson's disease with more severe motor symptoms and impairment of activities of daily living, were cognitively more impaired, were more often living alone, and had more hallucinations than those who continued to live at home. Duration of disease, levodopa dose, and gender distribution did not differ between the two groups. A Cox proportional hazards linear regression analysis showed that old age, functional impairment, dementia, and hallucinations were independent predictors of nursing home admission. CONCLUSIONS: Both motor and neuropsychiatric symptoms contributed to institutionalization, but the presence of hallucinations was the strongest predictor. This finding indicates it is possible that effective treatment of hallucinations may reduce the need for institutionalization in patients with Parkinson's disease.

Assessment of Mucosal Inflammation and Circulation in Response to Probiotics in Patients Operated with Ileal Pouch Anal Anastomosis for Ulcerative Colitis.

BACKGROUND: Pouchitis is a common and troublesome condition, and a disturbed microbiological flora and mucosal blood flow in the pouch have been suggested as possible causes. Laser Doppler flowmetry (LDF) has been used successfully to measure gastric and colonic mucosal perfusion in humans. The aim of this study was to evaluate the effect of intervention with probiotics on ileal pouch inflammation and perfusion in the pouch, assessed by endoscopy, histology, fecal calprotectin and LDF. METHODS: A fermented milk product (Cultura; 500 ml) containing live lactobacilli (La-5) and bifidobacteria (Bb-12) was given daily for 4 weeks to 10 patients operated with ileal-pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). Mucosal perfusion was measured with LDF and the degree of inflammation was examined at predefined levels of the distal bowel by endoscopy and histology. Stool samples were cultured for lactobacilli and bifidobacteria and calprotectin were measured before and after intervention. RESULTS: The LDF measurements were reproducible in the pelvic pouch at each of the predefined levels, but did not change after intervention. The mucosal perfusion was reduced in the distal compared to the proximal part of the pouch. Calprotectin levels did not change significantly after intervention. The median endoscopic score for inflammation was significantly reduced by 50% after intervention, whereas the histological score did not change significantly. CONCLUSION: The results suggest that probiotics primarily act superficially, with change of gross appearance of the mucosa at endoscopy, but without significant effect on histological picture, mucosal perfusion or faecal calprotectin, during a relatively short period of 4 weeks.

Statins for the reduction of risk of Alzheimer's disease.

BACKGROUND: : Two recent clinical reports describe an association between statin therapy and a reduction in the occurrence of Alzheimer's disease by as much as 70 %. One report is a cross-sectional analysis of discharges among three hospitals, and the other is a nested case control study drawn from ambulatory patients of general practitioners in the UK. Because neither study is a randomized trial, the association noted between statin therapy and a reduced incidence of Alzheimer's disease may have occurred because other factors, unaccounted for in the studies, may be present (so called bias) and be responsible for the observed association. However, there is an expanding body of biological and epidemiological data that makes it plausible that statin therapy may retard or prevent the pathogenesis and clinical expression of Alzheimer's disease. This review was initiated in order to find other clinical evidence that might support or refute the hypothesized benefit of statin therapy. OBJECTIVES: : The purpose is to review the evidence that treatment with statins reduces the risk of Alzheimer's disease. SEARCH STRATEGY: : The following data bases were searched: Specialised Register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (1966-2000/12), EMBASE (1980-2000/12), and Psych Info (1987-2000/11). Search terms included statins,lovastatin, pravastatin, simvastatin, alzheimer*, dement*, cogn*. SELECTION CRITERIA: : In order to be selected, trials needed to be randomized, doubled blinded, and of sufficient duration( probably years rather than weeks or months) to ascertain the preventive potential of statin therapy. DATA COLLECTION AND ANALYSIS: : Data were to be extracted independently by two reviewers and pooled where appropriate and possible. The pooled odds ratios (95% CI) or the average differences were to be estimated. MAIN RESULTS: : There were no randomized trials found in the search. REVIEWER'S CONCLUSIONS: : There is no good evidence to recommend statins for reducing the risk of Alzheimer's disease. There is, however, a growing body of biological, epidemiological, and limited but non-randomized clinical evidence that lowering serum cholesterol may retard the pathogenesis of Alzheimer's disease. Mounting the clinical studies to determine the potential benefit of statin therapy should be a high priority for future research agendas.

Statins for the prevention of Alzheimer's disease.

BACKGROUND: : Two recent clinical reports describe an association between statin therapy and a reduction in the occurrence of Alzheimer's disease by as much as 70 %. One report is a cross-sectional analysis of discharges among three hospitals, and the other is a nested case control study drawn from ambulatory patients of general practitioners in the UK. Because neither study is a randomized trial, the association noted between statin therapy and a reduced incidence of Alzheimer's disease may have occurred because other factors, unaccounted for in the studies, may be present (so called bias) and be responsible for the observed association. However, there is an expanding body of biological and epidemiological data that makes it plausible that statin therapy may retard or prevent the pathogenesis and clinical expression of Alzheimer's disease. This review was initiated in order to find other clinical evidence that might support or refute the hypothesized benefit of statin therapy. OBJECTIVES: : The purpose is to review the evidence that treatment with statins reduces the risk of Alzheimer's disease. SEARCH STRATEGY: : The following data bases were searched: Specialised Register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (1966-2000/12), EMBASE (1980-2000/12), and Psych Info (1987-2000/11). Search terms included statins,lovastatin, pravastatin, simvastatin, alzheimer*, dement*, cogn*. SELECTION CRITERIA: : In order to be selected, trials needed to be randomized, doubled blinded, and of sufficient duration( probably years rather than weeks or months) to ascertain the preventive potential of statin therapy. DATA COLLECTION AND ANALYSIS: : Data were to be extracted independently by two reviewers and pooled where appropriate and possible. The pooled odds ratios (95% CI) or the average differences were to be estimated. MAIN RESULTS: : There were no randomized trials found in the search. REVIEWER'S CONCLUSIONS: : There is no good evidence to recommend statins for reducing the risk of Alzheimer's disease. There is, however, a growing body of biological, epidemiological, and limited but non-randomized clinical evidence that lowering serum cholesterol may retard the pathogenesis of Alzheimer's disease. Mounting the clinical studies to determine the potential benefit of statin therapy should be a high priority for future research agendas.

D-cycloserine for Alzheimer's disease.

BACKGROUND: Evidence supports a role for the NMDA receptors in learning and memory. These can be modulated by the antibiotic D-cycloserine in such a way that the effect of the excitatory transmitter substance glutamate is enhanced. A study on healthy subjects pretreated with scopolamine to mimic Alzheimer's disease showed a positive effect of D-cycloserine at low doses. OBJECTIVES: To assess the efficacy and safety of D-cycloserine in patients with Alzheimer's disease. SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 14 June 2001 using the terms: cycloserine, D-cycloserine, Alzheimer*. SELECTION CRITERIA: Randomized, double-blinded and unconfounded trials comparing D-cycloserine with a control treatment. DATA COLLECTION AND ANALYSIS: Two larger and two smaller randomized controlled trials were identified. The clinical global impression scale was used in all studies and was a primary outcome measure. MAIN RESULTS: It was not possible to extract the results from the first phases of the two crossover studies and therefore the meta-analyses are based on the two parallel group 6-month studies. There was no indication of a positive effect favouring D-cycloserine for the numbers showing improvement at 6 months as assessed by the Clinical Global Impression for any dose. The number of withdrawals for any reason before end of treatment at 6 months was significantly in favour of placebo (fewer withdrawals) compared with D-cycloserine for dose levels of 30 mg/day (OR 2.94, 95% CI 1.52, 5.70) and 100 mg/day (OR 3.23, 95% CI 1.67, 6.25). There was no significant difference between treatment, (2, 10, 30, 100, or 200 mg/day) and placebo for the number of withdrawals due to adverse events by six months. REVIEWER'S CONCLUSIONS: The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease.

Screening by nurses for aphasia in stroke--the Ullevaal Aphasia Screening (UAS) test.

PURPOSE: In Norway, the speech therapist is responsible for the assessment of language impairment after stroke, but many hospitals have no speech therapist. This study therefore developed and evaluated a simple method to be used by nurses to detect aphasia in the acute stage of stroke; the Ullevaal Aphasia Screening (UAS) test. METHOD: The study was carried out among 37 stroke patients admitted to an acute stroke unit. They were assessed by nurses using the UAS, while the results of a comprehensive assessment by a speech therapist acted as the 'gold standard'. RESULTS: The predictive value of a positive test was 0.67 and that of a negative test 0.93; only two out of 28 who screened negative on the UAS were diagnosed with mild aphasia by the speech therapist. The weighted kappa coefficient of agreement was 0.83, indicating a strong agreement between the nurses' and speech therapists' scoring. The screening took 5-15 minutes to complete. CONCLUSION: The Ullevaal Aphasia screening test seems to be a short and valid screening instrument for aphasia in the acute stage of stroke, but further studies would be needed to substantiate the efficacy of the UAS test.

Association between impairments, self-care ability and social activities 1 year after stroke.

PURPOSE: To explore how motor and cognitive impairments relate to physical activities of daily living (PADL) and social activities after stroke. METHOD: The data related to 65 patients (mean age 74.4 years, 43% females), assessed 1 year after stroke by means of the Sødring Motor Evaluation of Stroke patients and the Assessment of Stroke and other Brain damage instruments. The self-care and social activities scales applied were the Barthel ADL Index and the Frenchay Activities Index (FAI). The association between impairment variables on the one hand and PADL and FAI scores on the other was estimated using Kendall rank correlations. RESULTS: Arm motor function correlated most strongly with the Barthel score (tau = 0.76), and visuospatial function came second (tau = 0.58). Factor analysis of the FAI produced three subscales: a 'domestic' factor most strongly related to arm motor function (tau = 0.49); 'outdoor' related to visuospatial ability (tau = 0.48); and 'hobby' which had no significant correlates. CONCLUSION: In the chronic phase of stroke, self-care and involvement in social activities relate most strongly to arm motor function and visuospatial ability. Outdoor activities depend mainly on visuospatial function.

Functional status among elderly Norwegian fallers living at home.

BACKGROUND AND PURPOSE: Falls and their after-effects are important contributors to disability in old age, but may be mitigated. The relationship between self-reported health and functioning and falling is examined in the present study. METHOD: The study design was cross-sectional. Data were collected from interviews with 431 community-dwelling Norwegian subjects aged 67-97 years. Physical health was assessed through items from the Multidimensional Functional Assessment of Older Adults (MFAQ), supplemented with the Body Mass Index (BMI). General health/psychosocial health was assessed with the General Health Questionnaire (GHQ-20), the Mini-mental State Examination, two general health items and items concerning mental and social health from the MFAQ. Falls during the last six months were registered and scored 0 (no falls), 1 (one fall) or 2 (two or more falls). RESULTS: During the previous six months 24.1% of subjects reported falling. Four variables: 'Perceived difficulty in keeping balance in walking', 'Troubled by heart pounding/shortness of breath', sum score on the GHQ factor 'Depression/hopelessness', and a higher value on BMI, were independently associated with number of falls reported. CONCLUSIONS: Score value on 'Perceived difficulty in keeping balance in walking' was the strongest significant predictor of falls in the present study. In contrast with other studies, no association between anxiety, general health and falling was observed.

Falls reported among elderly Norwegians living at home.

BACKGROUND AND PURPOSE: Norway has the highest reported incidence of hip fractures in western Europe. Little is known about the epidemiology of falls in Norway where the winter season is long and dark. The objective of this work was to study reported falls and their consequences among elderly Norwegians living at home. METHODS: A cross-sectional design was used for the study. Interviews were performed in the homes of 431 subjects, aged 67-97 years, living at home. Information on falling was gathered through six questions: whether the subject had fallen during the last six months, and if so, how many falls they had, where the last fall occurred, its perceived reason, the activity the subject had been engaged in when the fall occurred, and the resulting injury. RESULTS: In all, 24.1% of subjects reported falling during the last six months, and 9.5% had suffered more than one fall. Falls were most frequently linked to external events (63.1%). Outdoor falls were more frequent (59.0%; 95% CI = 51.2-82.0) than indoor falls. Older subjects were associated with more frequent indoor falls (p < 0.05), but gender was not significant. Fifty-one per cent of subjects had fallen while walking and 53% had suffered an injury from the last fall. In 13.4% of the women and 16.2% of the men, the last fall had resulted in a fracture. CONCLUSIONS: Compared to the results of other studies from industrialized Western countries, a similar crude fall rate, similar frequency and similar type of injury were found. However, in contrast to other studies, no gender difference was observed with regard to falling, place of falling and fracture rate.

Validation of the screening instrument for neuropsychological impairment in stroke.

BACKGROUND AND PURPOSE: Full neuropsychological assessment is time-consuming and exhausting for the patient in the early phase of stroke. The screening instrument for neuropsychological impairment in stroke (SINS) is a brief, bedside-applicable instrument designed to screen perceptual and cognitive dysfunction related to functional activities in stroke. It has been developed by physiotherapists to be incorporated in the general assessment of the patient. This study evaluates the validity of the method against a more extensive reference method assessing cognitive function. METHODS AND RESULTS: An unselected group of hospitalized stroke patients (N = 87) was assessed 10 days and 12 months after stroke. Factor analyses (52% explained variance), identified three factors: 'aphasia', 'apraxia' and 'visuocognitive dysfunction'. Receiver operating characteristics (ROC) curves demonstrated that for all factors, high specificity was maintained at the high sensitivity needed for a screening method. Kendall rank correlation coefficients between the scorings on the new instrument and the reference method were high. Effect size analysis showed that the ability of the new instrument to detect change in cognitive functioning during the first year was of the same magnitude as the reference method. CONCLUSIONS: SINS has a high sensitivity regarding cognitive dysfunction, as diagnosed by the more comprehensive and time-consuming reference method. The instrument would be useful as an initial step in the assessment of neuropsychological impairment in stroke patients.