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Biomedical subjects

I Skoog

Publications and source records attributed to I Skoog.

At least 55 records · Page 3Linked to original sources
PubMed2000

Study on COgnition and Prognosis in the Elderly (SCOPE): baseline characteristics.

The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multi-centre, prospective, randomized, double-blind, parallel-group study. The primary objective of SCOPE is to assess the effect of the angiotensin II type 1 (AT1) receptor blocker, candesartan cilexetil 8-16 mg once daily, on major cardiovascular events in elderly patients (70-89 years of age) with mild hypertension (DBP 90-99 and/or SBP 160-179 mmHg). The secondary objectives of the study are to test the hypothesis that antihypertensive therapy can prevent cognitive decline (as measured by the Mini Mental State Examination, MMSE) and dementia, and to assess the effect of therapy on total mortality, myocardial infarction (MI), stroke, renal function, and hospitalization. A total of 4964 patients from 15 participating countries were recruited during the randomization phase of SCOPE, exceeding the target population of 4000. The mean age of the patients at enrolment was 76 years, the ratio of male to female patients was approximately 1:2, and 52% of patients were already being treated with an antihypertensive agent at enrolment. The majority of patients (88%) were educated to at least primary school level. At randomization, mean sitting blood pressure values were SBP 166 mmHg and DBP 90 mmHg, and the mean MMSE score was 28. Previous cardiovascular disease in the study population included myocardial infarction (4%), stroke (4%) and atrial fibrillation (4%). Men, more often than women, had a history of previous MI, stroke and atrial fibrillation. A greater percentage of men were smokers (13% vs 6% in women) and had attended university (11% vs 3% of women). Of the randomized patients, 21% were 80 years of age. In this age group smoking was less common (4% vs 10% for 70-79-year-olds) and fewer had attended university (4% vs 7% for 70-79-year-olds). The incidence of MI was similar in both age groups. However, stroke and atrial fibrillation had occurred approximately twice as frequently in the older patients. The patients' mean age at baseline was similar in the participating countries, and most countries showed the approximate 1:2 ratio for male to female patients. There was also little inter-country variation in terms of mean SBP, DBP or MMSE score. However, there was considerable regional variation in the percentage of patients on therapy prior to enrolment.

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PubMed1999

APOE-epsilon4 count predicts age when prevalence of AD increases, then declines: the Cache County Study.

OBJECTIVE: To examine the prevalence of Alzheimer's disease (AD) and other dementias in relation to age, education, sex, and genotype at APOE. Recent studies suggest age heterogeneity in the risk of AD associated with the APOE genotype and a possible interaction between APOE-epsilon4 and female sex as risk factors. We studied these topics in the 5,677 elderly residents of Cache County, Utah, a population known for long life expectancy and high participation rates. METHODS: We screened for dementia with a brief cognitive test and structured telephone Dementia Questionnaire, then examined all individuals with apparent cognitive symptoms and a sample of others. We estimated age-specific prevalence of AD and other dementias and used multiple logistic regression models to describe relation of AD prevalence to age, sex, education, and APOE genotype. RESULTS: We found 335 demented individuals, 230 (69%) with definite, probable, or possible AD (positive predictive value versus autopsy confirmation 85%). The adjusted prevalence estimate for AD was 6.5% and for all dementias 9.6%. After age 90, the adjusted prevalence estimate for AD was 28% and for all dementias 38%. Regression models showed strong variation in AD prevalence with age, sex, education, and number of epsilon4 alleles (effect of epsilon2 not significant). Models were improved by a term for age-squared (negative coefficient) and by separate terms for interaction of age with presence of one or two epsilon4 alleles. An association of AD with female sex was ascribable entirely to individuals with epsilon4. CONCLUSIONS: In participants with no epsilon4 alleles, the age-specific prevalence of AD reached a maximum and then declined after age 95. In epsilon4 heterozygotes a similar maximum was noted earlier at age 87, in homozygotes at age 73. Female sex was a risk factor for AD only in those with epsilon4. The epsilon4 allele accounted for 70% of the population attributable risk for AD.

Age Distribution↗
PubMed1999

A 40-year follow-up of patients with obsessive-compulsive disorder [see commetns].

BACKGROUND: The long-term course of obsessive-compulsive disorder is insufficiently known. We studied the course of this disorder in patients who were followed up for 40 years. METHODS: Patients admitted with a diagnosis of obsessive-compulsive disorder to the Department of Psychiatry, Sahlgrenska University Hospital, Göteborg, Sweden, between 1947 and 1953 were examined by an experienced psychiatrist using a semistructured interview between 1954 and 1956 (n=251). The diagnosis was made according to the criteria of Schneider. A reexamination was performed by the same psychiatrist between 1989 and 1993 (n=122). In another 22 patients, the necessary information was obtained from close informants and medical records. The response rate in surviving patients was 82%. The mean length of follow-up from onset was 47 years. RESULTS: Improvement was observed in 83%, including recovery in 48% (complete recovery, 20%; recovery with subclinical symptoms, 28%). Among those who recovered, 38% had done so already in the 1950s. Forty-eight percent had obsessive-compulsive disorder for more than 30 years. Early age of onset, having both obsessive and compulsive symptoms, low social functioning at baseline, and a chronic course at the examination between 1954 and 1956 were correlated with a worse outcome. Magical obsessions and compulsive rituals were correlated with a worse course. Qualitative symptom changes within the obsessive-compulsive disorder occurred in 58% of the patients. CONCLUSION: After several decades, most individuals with obsessive-compulsive disorder improve, although most patients continue to have clinical or subclinical symptoms.

Adult↗
PubMed1999

Study on COgnition and Prognosis in the Elderly (SCOPE).

The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multicentre, prospective, randomized, double-blind, parallel-group study designed to compare the effects of candesartan cilexetil and placebo in elderly patients with mild hypertension. The primary objective of the study is to assess the effect of candesartan cilexetil on major cardiovascular events. The secondary objectives of the study are to assess the effect of candesartan cilexetil on cognitive function and on total mortality, cardiovascular mortality, myocardial infarction, stroke, renal function, hospitalization, quality of life and health economics. Male and female patients aged between 70 and 89 years, with a sitting systolic blood pressure (SBP) of 160-179 mmHg and/or diastolic blood pressure (DBP) of 90-99 mmHg, and a Mini-Mental State Examination (MMSE) score of 24 or above, are eligible for the study. The overall target study population is 4000 patients, at least 1000 of whom are also to be assessed for quality of life and health economics data. After an open run-in period lasting 1-3 months, during which patients are assessed for eligibility and those who are already on antihypertensive therapy at enrolment are switched to hydrochlorothiazide 12.5 mg o.d., patients are randomized to receive either candesartan cilexetil 8 mg once daily (o.d.) or matching placebo o.d. At subsequent study visits, if SBP remains >160 mmHg, or has decreased by <10 mmHg since the randomization visit, or DBP is >85 mmHg, study treatment is doubled to candesartan cilexetil 16 mg o.d. or two placebo tablets o.d. Recruitment was completed in January 1999. At that time 4964 patients had been randomized. All randomized patients will be followed for an additional 2 years. If the event rate is lower than anticipated, the follow-up will be prolonged.

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PubMed1999

Depression, cerebral atrophy, cognitive performance and incidence of dementia. Population study of 85-year-olds.

BACKGROUND: Hospital-based studies suggest that depression in old age relates to organic brain changes. AIMS: To determine whether these findings are confirmed in a population-based sample. METHOD: A population sample of non-demented 85-year-olds (227 mentally healthy and 62 with DSM-III-R depression were given a neuropsychiatric examination and computerised tomographic scans of the brain, and followed for three years. RESULTS: On the Mini-Mental State Examination, those with a low educational level with major depression performed worse than the mentally healthy; this distinction was not evident among those who had received higher education. Measures of brain atrophy were similar in depressed and mentally healthy individuals. The three-year incidence of dementia was increased in those with early-onset major depression. CONCLUSIONS: Higher education may protect against cognitive symptoms in depressed individuals. The association between depression and cerebral atrophy in the elderly is not very strong. The higher incidence of dementia in those with early-onset major depression may be due to a longer lifetime duration of depression, emphasising the importance of detecting and treating depression in the community.

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PubMed1999

Development of the EURO-D scale--a European, Union initiative to compare symptoms of depression in 14 European centres.

BACKGROUND: In an 11-country European collaboration, 14 population-based surveys included 21,724 subjects aged > or = 65 years. Most participating centres used the Geriatric Mental State (GMS), but other measures were also used. AIMS: To derive from these instruments a common depression symptoms scale, the EURO-D, to allow comparison of risk factor profiles between centres. METHOD: Common items were identified from the instruments. Algorithms for fitting items to GMS were derived by observation of item correspondence or expert opinion. The resulting 12-item scale was checked for internal consistency, criterion validity and uniformity of factor-analytic profile. RESULTS: The EURO-D is internally consistent, capturing the essence of its parent instrument. A two-factor solution seemed appropriate: depression, tearfulness and wishing to die loaded on the first factor (affective suffering), and loss of interest, poor concentration and lack of enjoyment on the second (motivation). CONCLUSIONS: The EURO-D scale should permit valid comparison of risk-factor associations between centres, even if between-centre variation remains difficult to attribute.

Age Distribution↗
PubMed1999

Depression symptoms in late life assessed using the EURO-D scale. Effect of age, gender and marital status in 14 European centres.

BACKGROUND: Data from surveys involving 21,724 subjects aged > or = 65 years were analysed using a harmonised depression symptom scale, the EURO-D. AIMS: To describe and compare the effects of age, gender and mental status on depressive symptoms across Europe. METHOD: We tested for the effects of centre, age, gender and marital status on EURO-D score. Between-centre variance was partitioned according to centre characteristics: region, religion and survey instrument used. RESULTS: EURO-D scores tended to increase with age, women scored higher than men, and widowed and separated subjects scored higher than others. The EURO-D scale could be reduced into two factors: affective suffering, responsible for the gender difference, and motivation, accounting for the positive association with age. CONCLUSIONS: Large between-centre differences in depression symptoms were not explained by demography or by the depression measure used in the survey. Consistent, small effects of age, gender and marital status were observed across Europe. Depression may be overdiagnosed in older persons because of an increase in lack of motivation that may be affectively neutral, and is possibly related to cognitive decline.

Age Distribution↗
PubMed1999

HRT and dementia.

The role of HRT and/or oestrogens in the aetiology, progression and prevention of neurodegenerative disorders is unclear. Various studies have been conducted in cells, animals and humans to better define these relationships. The following is a presentation of data on the role of oestrogens in the two most common dementia syndromes Alzheimer's Disease and vascular dementia. This review examines whether there is support for the hypothesis that the use of oestrogens reduces the risk for dementia and cognitive decline in a variety of experimental models. A literature search was performed using the following key words: oestrogen and dementia, oestrogen and Alzheimer, oestrogen and cognition, oestrogen and learning, and oestrogen and memory. The reference lists for the articles identified using these search strategies were examined. The strongest evidence for a beneficial effect comes from cell and animal studies. These suggest that treatment with oestrogens may influence the pathogenetic processes of AD, mainly by affecting the beta-amyloid metabolism, by promoting the activity of the cholinergic system, by reducing oxidative stress or cardiovascular risk. Observational studies give some support to the hypothesis that HRT may be protective for cognitive decline and dementia in the elderly, but the inherited methodological problems in these studies preclude any conclusions. The treatment trials published thus far have methodological problems that prohibit definite conclusions on the relationship between HRT and cognitive decline and dementia.

Alzheimer Disease↗
PubMed1998

Seven-year survival rate after age 85 years: relation to Alzheimer disease and vascular dementia.

OBJECTIVE: To investigate the survival rate in very elderly individuals in relation to Alzheimer disease, vascular dementia, and other mental and physical disorders. DESIGN: A 7-year longitudinal survey. SETTING: Community and institutions in Gothenburg, Sweden. PARTICIPANTS: A representative sample of 494 people aged 85 years. MAIN OUTCOME MEASURES: Results of neuropsychiatric and physical examinations, key informant interview, and computed tomographic scan of the head. Information on mortality was obtained from the parish office. RESULTS: The 7-year survival rate was higher in women (34.5%) than in men (20.3%). Alzheimer disease and vascular dementia predicted 30.7% of deaths in men and 49.7% of deaths in women according to a calculation of population attributable risk (PAR). A regression analysis showed that mortality in men was predicted by the presence of chronic obstructive lung disease (PAR, 18.8), Alzheimer disease (PAR, 16.0), vascular dementia (PAR, 14.7), cancer of the gastrointestinal tract (PAR, 10.2), and skin cancer (PAR, 6.2), and in women by vascular dementia (PAR, 29.4), Alzheimer disease (PAR, 20.3), cerebrovascular disorder (PAR, 12.1), congestive heart failure (PAR, 8.5), hypertension (PAR, 8.0), myocardial infarction (PAR, 6.5), and cancer of the gastrointestinal tract (PAR, 4.3). Life expectancy decreased with severity of dementia, although survival time in individuals with mild Alzheimer disease was not different from that in individuals without dementia. CONCLUSIONS: In extreme old age, Alzheimer disease and vascular dementia influence the mortality rate considerably. However, mild Alzheimer disease does not influence longevity, at least not during the first 7 years. These findings have important public health implications.

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PubMed1998

A population study of apoE genotype at the age of 85: relation to dementia, cerebrovascular disease, and mortality.

OBJECTIVES: To study the association of apoE genotypes with dementia and cerebrovascular disorders in a population based sample of 85 year old people. METHODS: A representative sample of 85 year old people (303 non-demented, 109 demented) were given a neuropsychiatric and a medical examination and head CT. The apoE isoforms were determined. Dementia was diagnosed according to DSM-III-R. RESULTS: At the age of 85, carriers of the apoE epsilon4 allele had an increased odds ratio (OR) for dementia (1.9; p<0.01) and its subtypes Alzheimer's disease (1.9; p<0.05) and vascular dementia (2.0; p<0.05). Among those categorised as having vascular dementia, the apoE epsilon4 allele was associated with mixed Alzheimer's disease-multi-infarct dementia (OR 6.5; p<0.05), but not with pure multi-infarct dementia (OR 1.5; NS). Only carriers of the apoE epsilon4 allele who also had ischaemic white matter lesions on CT of the head had an increased OR for dementia (OR 6.1; p=0.00003), and its main subtypes Alzheimer's disease (OR 6.8; p=0.002) and vascular dementia (OR 5.6; p=0.0007), whereas carriers of the apoE epsilon4 allele without white matter lesions had an OR for dementia of 1.0 (OR for Alzheimer's disease 1.8; NS and for vascular dementia 0.6; NS) and non-carriers of the apoE epsilon4 allele with white matter lesions had an OR for dementia of 2.2; NS (OR for Alzheimer's disease 2.7; NS and for vascular dementia 1.6; NS). The apoE allele variants were not related to mortality or incidence of dementia between the ages of 85 and 88. The epsilon2 allele was related to a higher prevalence of stroke or transient ischaemic attack at the age of 85 (OR 2.1; p<0.05) and a higher incidence of multi-infarct dementia during the follow up (OR 2.9; p<0.05). CONCLUSIONS: Neither the apoE epsilon4 allele nor white matter lesions are sufficient risk factors by themselves for dementia at very old ages, whereas possession of both these entities increases the risk for Alzheimer's disease and vascular dementia substantially.

Aged↗
PubMed1998

Status of risk factors for vascular dementia.

The two most common causes of vascular dementia (VAD) are dementia evolving in connection with multiple small or large strokes and dementia related to ischemic white-matter lesions (WMLs) of the brain. The knowledge about risk factors for these disorders is still scarce. Besides sharing risk factors with stroke, dementia with multiple small or large brain infarcts is also associated with non-vascular risk factors such as high alcohol consumption, psychological stress in early life, lower formal education, blue collar occupation, and occupational exposures. Risk factors for dementia in stroke victims include stroke-related and non-stroke related risk factors. Non-stroke-related factors are similar to those found in Alzheimer's disease. The main risk factors for ischemic WMLs are hypertension or increased blood pressure, but WMLs have also been associated with a number of other vascular risk factors. In recent years, Alzheimer's disease (AD) has also been reported to be associated with vascular risk factors, including hypertension, coronary heart disease, atrial fibrillation, diabetes mellitus, and WMLs. Although these associations may reflect an overdiagnosis of AD in cases with silent cerebrovascular disease, or that cerebrovascular disease increases the possibility that individuals with Alzheimer lesions will express a dementia syndrome, there are also alternative explanations. AD and cerebrovascular disease may for instance share similar risk factors or etiologic pathways. The pathogenetic implications for the association between AD and vascular factors need to be further explored. There is also a need for more studies on risk factors for VAD and risk factors for dementia in stroke samples, as well as studies on non-vascular risk factors for ischemic WMLs.

Brain↗
PubMed1998

A review on blood pressure and ischaemic white matter lesions.

Hypertension or high blood pressure is constantly reported to be the main risk factors for ischaemic white matter lesions (WMLs). These lesions show the histopathological picture of diffuse demyelination and moderate loss of axons in subcortical structures. The main hypothesis regarding the association between high blood pressure and ischaemic WMLs is that long-standing hypertension causes lipohyalinosis of the media and thickening of the vessel walls with narrowing of the lumen of the small perforating arteries and arterioles which nourish the deep white matter. Episodes of hypotension may then lead to hypoperfusion and hypoxia-ischaemia in the white matter. In line with this, low blood pressure has also been reported to be a risk factor for WMLs. However, also other pathogenetic mechanisms may be involved. Hypertension may cause disturbances in the blood-brain barrier, which may cause lesions in the white matter by cerebral oedema, by activation of astrocytes or by destructive enzymes or other poisons which pass through the damaged vessel walls. The renin-angiotensin system is an example of a system that may be involved in the pathogenesis of both hypertension and arteriosclerosis. Its effector peptide angiotensin II has several blood-pressure-increasing effects, such as direct vasoconstriction and activation of the sympathetic nervous system. It also promotes hyperplasia and hypertrophy in vascular smooth muscle cells. Recently an association between hypertension and Alzheimer's disease has been reported. It is not clear whether this may be the reason for the common occurrence of WMLs in cases of late-onset Alzheimer's disease, as Alzheimer's disease may also cause lesions in the cerebral microvasculature. The association between WMLs and hypertension may thus be mediated through several different pathogenetic pathways.

Animals↗
PubMed1998

A population-based study on blood pressure and brain atrophy in 85-year-olds.

In the general population, mean systolic and diastolic blood pressure increases up to age 75 years but decreases thereafter. The brain has a role in blood pressure regulation; it is not clear whether the cerebral changes that occur with aging contribute to the decline in blood pressure in the very elderly. We examined a population-based sample of 484 85-year-old persons (344 nondemented and 140 demented, 61 with Alzheimer's disease, 65 with vascular dementia, and 14 with other types of dementia) with a neuropsychiatric examination and blood pressure measurements. Dementia was diagnosed according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders, edition 3, revised. Brain atrophy was measured by CT of the brain. In the nondemented group, frontal (r=-0.18, P=0.037) and parietal (r=-0.23, P=0.008) cortical atrophy and bifrontal ratio (r=-0.20, P=0.013) were associated with lower systolic blood pressure, and frontal (r=-0.23, P=0.010) and parietal (r=-0.24, P=0.008) cortical atrophy and bifrontal ratio (r=-0.23, P=0.006) with lower diastolic blood pressure. Systolic blood pressure was lower in subjects with Alzheimer's disease and vascular dementia, and diastolic blood pressure was lower in those with vascular dementia compared with the nondemented. Systolic (r=-0.27, P<0.0001) and diastolic (r=-0.10, P=0.020) blood pressure was negatively correlated to dementia severity. In the demented subjects, frontal cortical atrophy was correlated to lower diastolic blood pressure (r=-0.21, P=0.043). Our findings suggest that age-related changes in brain structure may contribute to the decrease in blood pressure in the very elderly and that low blood pressure in dementia disorders is mainly a secondary phenomenon.

Aged↗
PubMed1998

A population study on blood-brain barrier function in 85-year-olds: relation to Alzheimer's disease and vascular dementia.

We investigated blood-brain barrier (BBB) function in relation to Alzheimer's disease (AD) and vascular dementia (VAD) in the very elderly. Sixty-five 85-year-old persons from a population-based sample were followed for 3 years; 29 were demented at age 85 (13 with AD, 14 with VAD, and 2 with other dementias), 7 developed dementia during follow-up, and 29 remained nondemented. CSF/serum albumin ratio was used as as a measure of BBB function. Dementia was defined according to the DSM-III-R, AD according to the NINCDS-ADRDA criteria, and VAD according to the NINDS-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria. Mean CSF/serum albumin ratio was higher in all dementias (8.5 +/- 4.3; p = 0.007) and in the subtypes AD (8.9 +/- 5.3; p = 0.046) and VAD (8.7 +/- 3.5; p = 0.002) than in nondemented individuals (versus 6.5 +/- 2.0), but it was not related to dementia severity. Nondemented women at age 85 (n = 3) who developed dementia during the follow-up had a higher CSF/serum albumin ratio than those not developing dementia (10.4 +/- 2.0 versus 6.0 +/- 1.9; p = 0.007). Nondemented individuals lacking the apolipoprotein E epsilon3 allele (n = 4) had a higher CSF/serum albumin ratio (9.3 +/- 0.8 versus 6.6 +/- 2.1; p = 0.029) than other individuals. A relative BBB dysfunction is associated with both AD and VAD among very elderly individuals. This finding is possibly found early in the disease before the onset of clinical dementia.

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PubMed1997

Apolipoprotein E in cerebrospinal fluid in 85-year-old subjects. Relation to dementia, apolipoprotein E polymorphism, cerebral atrophy, and white matter lesions.

OBJECTIVE: To further elucidate the pathogenetic role of apolipoprotein E (Apo E) in degenerative brain disorders, we analyzed cerebrospinal fluid (CSF) levels of Apo E in 85-year-old subjects with dementia disorders. DESIGN: Survey. SETTING: Community. PARTICIPANTS: Population-based sample of 27 demented (12 with Alzheimer disease [AD]; 13, vascular dementia [VAD]; and 2, other types of dementia) and 35 nondemented individuals. MAIN OUTCOME MEASURES: Cerebrospinal fluid levels of Apo E, Apo E polymorphism, and brain atrophy and white matter lesions (WMLs) measured by computed tomography (CT) of the brain. Dementia was defined according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria; AD, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria; and VAD, National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neuroscience criteria. RESULTS: The mean (+/- SD) CSF levels of Apo E were lower in the AD (2.6 +/- 1.5 mg/L; P < .02) and VAD groups (2.5 +/- 0.9 mg/L; P < .002) than in the nondemented group (3.8 +/- 1.7 mg/L). Cerebrospinal fluid levels of Apo E decreased with increasing severity of dementia and with increasing temporal cortical and central frontal atrophy. In nondemented individuals, CSF levels of Apo E decreased with increasing degree of WMLs. Cerebrospinal fluid levels of Apo E were not influenced by the Apo E4 isoform. CONCLUSIONS: Whether our finding of an association between low CSF levels of Apo E and dementia disorders (both degenerative, such as AD, and vascular, such as VAD) is related to the pathogenesis of these disorders or is a secondary consequence of the disease process remains to be established. Although statistical correlations do not give direct evidence of causal relations, the correlations between CSF level of Apo E and severity of dementia and cortical atrophy suggest that CSF level of Apo E follows the disease process.

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PubMed1997

The relationship between blood pressure and dementia: a review.

Hypertension has been related to the development of dementia, including Alzheimer's disease, and cognitive dysfunction in middle-aged and elderly populations. One possible explanation is that hypertension is a risk factor for cerebral infarcts and ischaemic subcortical white-matter lesions. Hypertension may also give rise to a blood-brain barrier dysfunction, which has been suggested to be involved in the aetiology and pathogenesis of Alzheimer's disease. Other possible explanations for the association are shared risk factors, such as psychological stress, and the formation of free oxygen radicals. Low blood pressure has also been hypothesized to give rise to brain damage and dementia. However, the brain is involved in blood pressure regulation and dementia disorders may therefore influence the blood pressure. The findings of an association between hypertension and dementia may have implications for prevention and treatment.

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