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Biomedical subjects

H Basun

Publications and source records attributed to H Basun.

At least 37 records · Page 2Linked to original sources
PubMed1998

Wide range of disease onset in a family with Alzheimer disease and a His163Tyr mutation in the presenilin-1 gene.

OBJECTIVES: To describe clinical and genealogical data of a Swedish family with a His163Tyr mutation in the presenilin-1 gene (PS1) and to study the Alzheimer disease (AD) penetrance in this family. DESIGN: Interviews with relatives, studies of medical records, analysis of pedigree, physician examination of the affected individuals, and comparison with other families affected by AD with PS1 mutations. SETTING: Large university-affiliated hospital. PATIENTS AND OTHER PARTICIPANTS: Individuals with a His163Tyr mutation in PS1 and their relatives. RESULTS: A study of this family with a history of very early AD onset (mean age, 47 years) has been previously published, but an investigation of the extended family revealed a new pattern of onset, with a mean age at onset of 54 years (range, 44-65 years). In general, families with AD show a tight cluster of age at onset with high penetrance of the disease. However, in this family, an individual whose child carries the PS1 mutation died at age 67 years free from cognitive symptoms, indicating a very late age at onset or nonpenetration of the disease. No association between age at onset and disease duration was found. Furthermore, the disease duration did not differ between those having an early onset compared with those having a late onset. The earliest clinical manifestations were deficits in memory function and disorientation in time and place. Myoclonic jerks and epileptic seizures were common symptoms later in the disease. CONCLUSION: The large range in age at onset in this family with a uniform genetic basis for the disease, a His163Tyr mutation in PS1, supports the existence of other unknown genetic or environmental factors of importance for the expression of the AD phenotype.

Age of Onset↗
PubMed1998

Mild cognitive impairment--an early stage of Alzheimer's disease?

The hypothesis that mild cognitive impairment (MCI) represents an early stage of Alzheimer's disease (AD) was investigated by reviewing recent research from three sources: asymptomatic and symptomatic individuals carrying mutations that cause AD, hospital-samples of non-demented patients with MCI at the initial examination that are followed longitudinally, and community-based incident cases of AD. Studies with asymptomatic mutation carriers of the amyloid precursor protein and presenilin 1 gene have shown a linear and disease-related decline in most cognitive functions that begins approximately 10 years before the expected clinical onset of AD. However, there is considerable overlap between the level of impairment for mutation carriers and non-carriers of the same age during the early preclinical stage of AD. Hospital-based longitudinal studies have shown that non-demented individuals with isolated mild episodic memory impairment may develop clinically diagnosed AD with widespread cognitive deficits in a few years time. Community-based epidemiological studies on the incidence of AD demonstrate that indices of episodic memory, in addition to measures of general cognitive functioning, are useful in predicting early AD. In contrast, subjective memory impairment or age-associated memory impairment are less powerful predictors of future dementia development. In summary, there is converging evidence to demonstrate that preclinical AD is characterized by a common behavioral phenotype, with cognitive decline in several domains, predominantly in episodic memory. The decline appears to start many years before the clinical onset of AD. Moreover, the progression of the impairment appears to be continuous. Finally, this pattern of performance generalizes across etiology of AD (familial or sporadic), clinical onset (early or late), sample composition (hospital or community), and method of assessment.

Aged↗
PubMed1998

Three-year changes in cognitive performance as a function of apolipoprotein E genotype: evidence from very old adults without dementia.

This study examined whether baseline cognitive performance and 3-year longitudinal changes were influenced by apolipoprotein E epsilon 4 (APOE-epsilon 4) allele. Participants consisted of 20 APOE-epsilon 4 (2 epsilon 2/epsilon 4; 17 epsilon 3/epsilon 4; 1 epsilon 4/epsilon 4) and 54 non-epsilon 4 (12 epsilon 2/epsilon 3; 42 epsilon 3/epsilon 3) very old adults without dementia (M = 81.82 +/- 5.06 years) participating in a population-based longitudinal study. Cognitive performance was indexed by the Mini-Mental State Examination and multiple indexes of memory, visuospatial, and verbal performance. The results indicated no significant baseline differences between the 2 APOE groups in any cognitive performance measure. However, analyses revealed that the APOE-epsilon 4 group experienced greater negative change in recognition memory for faces and words. Changes in tasks assessing other abilities did not vary as a function of APOE status. The authors concluded that APOE-epsilon 4 status may not influence cognitive performance in adults without dementia and speculated that when such effects do occur (e.g., decline in recognition memory), these may be related to impending dementia, rather than to the influence of the specific genotype on cognition in normal aging.

Aged↗
PubMed1998

Brain volumes and regional cerebral blood flow in carriers of the Swedish Alzheimer amyloid protein mutation.

As a preliminary part of a longitudinal clinical study of carriers of the Swedish amyloid precursor protein (APP) 670/671 mutation, 13 members of a family were investigated with magnetic resonance imaging (MRI) brain volumetry and single photon emission computed tomography (SPECT) cerebral blood flow (CBF) measurements. Five of the family members were mutation carriers; eight were not carriers. Two carriers were younger than 40 years of age and had no evidence of cognitive dysfunction or structural or functional brain changes. One carrier with 4 years to expected disease onset showed poor performance in episodic memory tests and also slightly low temporal lobe CBF, although there were no clearly abnormal findings. One carrier with mild Alzheimer disease (AD) had no clear structural brain changes, although CBF measurements showed clear reduction of temporal lobe CBF. One carrier with severe AD had both temporal lobe atrophy and CBF reduction. This indicates that in carriers of the APP 670/671 mutation, reduction of regional CBF is more severe than regional atrophy. The clearest change related to development of clinical AD was a reduction of CBF in the basal and lateral temporal lobes. Further longitudinal studies of these subjects are needed to confirm these preliminary findings, which might provide important data regarding early brain changes in AD.

Adult↗
PubMed1997

Depression and dementia in relation to apolipoprotein E polymorphism in a population sample age 75+.

The aim of this study was to define the co-occurrence of depression and dementia in relation to apolipoprotein E (APOE) polymorphism. Physicians extensively examined 806 persons aged 78 years and over. DNA was extracted from peripheral white blood cells, and APOE genotype was determined using a microsequencing method on microtiter plates. The prevalence of dementia was 22.8% and was found to increase with the number of epsilon 4 alleles present. Depression was found in 11.4% of the demented subjects compared to 3.5% of the nondemented subjects. The overrepresentation of depression in demented subjects was found for each of the common genotypes. Depression was not strongly associated with APOE polymorphism. In spite of the association between dementia and APOE polymorphism, as well as dementia and depression, there was no association between APOE polymorphism and depression.

Aged↗
PubMed1997

Mapping of a disease locus for familial rapidly progressive frontotemporal dementia to chromosome 17q12-21.

Familial frontotemporal dementia (FTD) is a complex disorder with lack of distinctive histopathological markers found in other types of dementia. Most of the linkage reports from FTD families map the disease loci to chromosome 17q21-22. However, FTD is genetically heterogeneous, as linkage also has been reported to chromosome 3. In the present study, we investigated the genetics of a Swedish family with an early-onset type of rapidly progressive FTD, associated with muscular rigidity and akinetic movements. Neuropathological features such as severe frontal lobe degeneration, spongy changes, and gliosis were present in affected family members. We here report probable linkage to chromosome 17q12-21 with a maximum two-point lod score of 2.76 at theta = 0 for marker D17S806, and a peak multipoint lod score of 2.86 for the same marker. Linkage to chromosome 3 was excluded, as two-point lod scores of -2.79, and -2.27 at theta = 0.01 for markers D3S1603 and D3S1552, respectively, were obtained. Sequencing of the translated exons of a strong candidate gene in the linked region of chromosome 17, the tau gene, failed to identify any mutations segregating with the disease.

Age of Onset↗
PubMed1997

Cerebrospinal fluid apolipoprotein E (apoE) levels in Alzheimer's disease patients are increased at follow up and show a correlation with levels of tau protein.

Apolipoprotein E (apoE) levels were compared in cerebrospinal fluid (CSF) taken on two occasions, with an average 15 months follow up, from groups of patients with Alzheimer's disease (AD: n = 18), mild cognitive impairment (MCI; n = 9) and other dementia disorders (ODD; n = 9). In these groups, CSF apoE levels were between 2-3-fold higher than values for a group of 27 healthy age-matched controls. CSF apoE levels in the AD group were significantly increased at follow up, compared to levels obtained on the first sampling occasion. For the same cases it had been shown previously that CSF tau protein levels were increased at follow up [Blomberg, M., Jensen, M., Basun, H., Lannfelt, L. and Wahlund, L-O., Neurosci. Lett., 214 (1996) 163-166]. The AD, but not MCI, ODD or control groups, also showed statistically significant correlations between CSF apoE and tau protein levels at both the first (r = 0.585, P < 0.01) and follow up (r = 0.695, P > 0.001 ) samplings. It is concluded that CSF measures of both apoE and tau may reflect an intimate relationship between these two proteins in AD and could prove useful in monitoring the progression of this condition.

Adult↗
PubMed1997

No difference in cerebral glucose metabolism in patients with Alzheimer disease and differing apolipoprotein E genotypes.

BACKGROUND: Recent findings of a reduced cerebral metabolic rate of glucose (CMRGlu) in at-risk relatives of patients with Alzheimer disease (AD) who carry the apolipoprotein E (APOE) epsilon 4 allele suggest a causative role for the E4 isoform in cognitive changes that lead to AD. It is not known whether epsilon 4 allele-associated deficits exist in patients with clinical AD. OBJECTIVE: To determine whether distinct patterns of cerebral hypometabolism exist in patients who carry the epsilon 4 allele. PATIENTS AND METHODS: Information on the CMRGlu and APOE genotype was available for 46 patients at a memory disorders clinic: 31 patients were diagnosed as having probable AD, 3 demented patients did not meet criteria for AD, and 12 patients had mild memory complaints. Positron emission tomography with the use of 18F-fludeoxyglucose was used to calculate the CMRGlu in the frontal and temporoparietal regions of the cortex. Estimates were standardized to the sensorimotor area of the cortex. Linear regression models were constructed to relate the APOE genotype to the CMRGlu, adjusting for cognitive status (ie, the Mini-Mental State Examination score). RESULTS: Distinct patterns of the CMRGlu did not emerge for patients with different APOE genotypes. Bilateral deficits in the CMRGlu were found in the patients with AD. Left-right asymmetry was found in 8 of 12 patients with mild memory complaints: 7 of 8 had CMRGlu ratio less than 0.85 in the left side of the temporoparietal region of the cortex. CONCLUSIONS: The APOE epsilon 4 allele does not appear to be associated with specific deficits in brain metabolism in patients with AD despite evidence that the epsilon 4 allele is associated with preclinical alterations. This finding is consistent with previous epidemiologic results that have demonstrated a higher risk for AD in carriers of the epsilon 4 allele, but no change in the rate of progression of AD.

Adult↗
PubMed1997

Clinical characteristics of a chromosome 17-linked rapidly progressive familial frontotemporal dementia.

OBJECTIVE: To describe symptoms, signs, neuroimaging results, and neuropathologic findings in patients from a family with chromosome 17q21-linked autosomal dominant frontotemporal dementia. DESIGN: Multiple case report with genetic investigations. SUBJECTS: The disease was observed in a Swedish family and documented in 3 generations. Four siblings are described in this article. RESULTS: A rapidly progressive dementia with genetic linkage to chromosome 17q21 was observed. The mean age of onset was 51 years and the average duration of disease to death was 3 years. Two patients started with speech disturbances leading to a progressive, nonfluent aphasia, 1 patient had onset symptoms of leg apraxia and akinesia and muscular rigidity, and in 1 patient reckless driving was the first symptom. Loss of spontaneous speech developed later in all patients and emotional bluntness in 3 of the patients. Cerebral perfusion was decreased in the frontal areas in all patients. In the person with apraxia as the onset symptom, the cerebral blood flow was also diminished in the left hemisphere, where a slight atrophy was detected on magnetic resonance imaging scans. At the postmortem examination, slight gliosis of the parietal lobes was observed in this patient. In all patients there was a frontocentral degeneration of the cortex with discrete microvacuolation and gliosis. CONCLUSION: Clinical features of frontotemporal dementia, parkinsonism, an early age of onset, a rapid disease progression, and variable onset symptoms were seen in these patients. Two other clinically distinct diseases, dementia with pallido-ponto-nigral degeneration and a disinhibition-dementia-parkinsonism-amyotrophy complex, have recently been mapped to chromosome 17q21. In the family described in this article, genetic linkage was detected to the same region, suggesting the possibility that these diseases may originate from pathogenic mutations in the same gene.

Chromosomes, Human, Pair 17↗
PubMed1997

Cerebrospinal fluid levels of alpha-secretase-cleaved soluble amyloid precursor protein mirror cognition in a Swedish family with Alzheimer disease and a gene mutation.

OBJECTIVE: To explore the relationship between possible biological markers of Alzheimer disease that are related to amyloid metabolism and mental functions. PARTICIPANTS: Twelve individuals from a Swedish family with Alzheimer disease and a double mutation at codons 670/671 of the amyloid precursor protein gene participated in the study. DESIGN: Cerebrospinal fluid levels of alpha-secretase cleaved soluble amyloid precursor protein (alpha-sAPP), total sAPP, and amyloid beta-peptide were correlated with data on multiple cognitive functions that covered the whole range of human performance. SETTING: The Alzheimer's Disease Research Centre, Department of Clinical Neuroscience, Section of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden. RESULTS: There were highly significant linear correlations between low levels of alpha-sAPP and poor performance on neuropsychological tests that assessed intelligence, verbal and visuospatial functions, memory, and attention. Within the group of nonmutation carriers, significant correlations were also obtained between the levels of alpha-sAPP and cognitive functions. A less striking association was seen between the levels of total sAPP and cognition. No association was found between the levels of amyloid beta-peptide and cognition. CONCLUSIONS: The strong relationship between alpha-sAPP levels and cognition in both patients with Alzheimer disease and normal-aging persons may imply that alpha-sAPP is involved in basic protective brain processes. Alternatively, less amyloid beta-peptide amounts are produced, leading to diminished plaque formation, when alpha-sAPP is generated.

Adult↗
PubMed1996

Increasing cerebrospinal fluid tau levels in a subgroup of Alzheimer patients with apolipoprotein E allele epsilon 4 during 14 months follow-up.

The concentration of tau protein is elevated in the cerebrospinal fluid (CSF) in Alzheimer's disease (AD), suggesting that CSF tau may be a useful biochemical diagnostic marker for this disorder. We investigated CSF tau concentrations on two occasions in AD (n = 18), mild cognitive impairment (MCI, n = 9) and other dementing disease (OD, n = 9) by ELISA (Innotest hTau Antigen, Innogenetics, Belgium). Tau levels were statistically significant higher in the AD group than in MCI and OD groups on both occasions. Twelve of the AD patients showed increasing values of tau at follow-up and six demonstrated diminished values. All AD patients with increasing tau were carriers of one or two epsilon 4 alleles of the apolipoprotein E (APOE, gene. Of those AD cases with decreasing tau levels only three individuals had the epsilon 4 allele, a difference that was statistically significant (P < 0.05). These findings suggest that there may be apolipoprotein E (apoE) isoform-specific differences of tau regulation in AD.

Adult↗
PubMed1996

Apolipoprotein E genotype determines survival in the oldest old (85 years or older) who have good cognition.

OBJECTIVE: To quantify the influence of apolipoprotein E (APOE) polymorphism on cognition and survival in a population sample aged 75 years or older. DESIGN: The Kungsholmen Project established a cohort of 1810 residents in a district in Stockholm, Sweden, aged 75 years or older in 1987. Information on cognition at cohort inception is available for all subjects. Subjects were followed up for mortality to January 1, 1995. SUBJECTS: Included in this study are 1077 subjects (of 1124 genotyped for APOE) with the common epsilon 2/3, epsilon 3/3, and epsilon 3/4 APOE genotypes. RESULTS: The odds of cognitive impairment for the epsilon 3/4 vs epsilon 3/3 genotype declined with age: 4.8 for age 75 through 79 years; 1.7 for age 80 through 84 years; and 1.0 (i.e., no association) for age 85 years or older. Despite this association, APOE polymorphism did not significantly predict survival in subjects younger than 85 years, nor did it predict survival in subjects 85 years or older who were cognitively impaired. Instead, survival varied fourfold with respect to APOE polymorphism in those 85 years or older who had good cognition: Mortality in subjects with the epsilon 2/3 genotype was half that in those who carried the epsilon 3/3 genotype (hazard ratio, 0.5; 95% confidence interval, 0.2 to 0.9), and mortality in subjects with the epsilon 3/4 genotype was twice that in those who carried the epsilon 3/3 genotype (hazard ratio, 2.0; 95% confidence interval, 1.1 to 3.5). This fourfold variation resulted in 2-year differences in survival. CONCLUSIONS: The minor sequence variation in the apolipoprotein E isoforms resulted in a fourfold difference in the risk of death among the oldest old (age > or = 85 years) with good cognition. The observed variation in mortality was unlikely to have been caused by cognitive impairment, as APOE polymorphism was not a risk factor for cognitive impairment in this age group.

Age Factors↗
PubMed1996

A follow-up study of five cases of aluminosis.

Five men were investigated after having pulmonary aluminosis due to exposure to aluminium pyrotechnic flake powder during the late 1940s. Two of the men had died 6 years and 20 years after exposure respectively, due to their lung disease. One man had died from heart failure 34 years after the end of exposure. Today, more than 40 years after exposure, two men were available for investigation. They had no respiratory symptoms and their vital lung capacities had not deteriorated during these years. One of the two survivors had developed a dementia with motor disturbances, which is not consistent with Alzheimer's dementia. This man had a very high concentration of aluminium in his cerebrospinal fluid. The other survivor had a normal concentration and was not demented.

Adult↗
PubMed1996

MRI in successful aging, a 5-year follow-up study from the eighth to ninth decade of life.

PURPOSE: This study aimed at evaluate the effect of aging on the central nervous system in "successfully aged" elderly subjects. The brain was studied with magnetic resonance imaging and neuropsychological tests at three different occasions during a time period of 5 yr. MATERIALS AND METHODS: Twenty-four successfully aged elderly were repeatedly examined with cerebral MRI and neuropsychological tests. The first examinations were performed in 1987 and then followed-up in 1989 and 1993. Two different MRI systems were used, in 1987 and 1989, a system operating at 0.02 T and in 1993 a system operating at 0.5 T. Ten subjects (42%) did not participate in the follow-up studies. MRI was used to study the degree of and increase in signal hyperintensities in the cerebrum, the basal ganglia, and in the infratentorial areas as well as changes in the volumes of the cerebro spinal fluid (CSF) spaces. RESULTS: At the start of the study in 1987, mild signal hyperintensities were observed in 11 of the 13 subjects who completed the follow up study. A modest increase in signal hyperintensity was found in almost all of the subjects, with the increases in cerebral white matter and basal ganglia signal hyperintensity being statistically significant (p < .03 and p < .05). The increases in periventricular hyperintensity and the hyperintensity from the infratentorial areas did not reach statistical significance. Volumes of the lateral ventricles and the frontal CSF spaces increased significantly (p < .03 in both cases) during the observation period, whereas the other volumes remained unchanged. The neuropsychological tests were unchanged during the observation period with the exception of the psychomotor capacity, which deteriorated. No statistical significant correlations were seen between the degree of or increase in signal hyperintensities and results from any of the neuropsychological tests. CONCLUSION: During a 5-yr observation of successfully aged elderly it was found that there was a mild increase in signal hyperintensity in the cerebral white matter and basal ganglia, as well as an increase in the frontal and ventricular CSF volumes. These changes were not related to changes in psychometric test results, nor were they related to the clinical outcome during the time of observation.

Aged↗