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Biomedical subjects

A J Dalton

Publications and source records attributed to A J Dalton.

At least 19 recordsLinked to original sources
PubMed2000

Are hereditary hemochromatosis mutations involved in Alzheimer disease?

Mutations in the class I-like major histocompatibility complex gene called HFE are associated with hereditary hemochromatosis (HHC), a disorder of excessive iron uptake. We screened DNA samples from patients with familial Alzheimer disease (FAD) (n = 26), adults with Down syndrome (DS) (n = 50), and older (n = 41) and younger (n = 52) healthy normal individuals, for two HHC point mutations-C282Y and H63D. Because the apolipoprotein E (ApoE) E4 allele is a risk factor for AD and possibly also for dementia of the AD type in DS, DNA samples were also ApoE genotyped. Chi-squared analyses were interpreted at the 0.05 level of significance without Bonferroni corrections. In the pooled healthy normal individuals, C282Y was negatively associated with ApoE E4, an effect also apparent in individuals with DS but not with FAD. Relative to older normals, ApoE E4 was overrepresented in both males and females with FAD, consistent with ApoE E4 being a risk factor for AD; HFE mutations were overrepresented in males and underrepresented in females with FAD. Strong gender effects on the distribution of HFE mutations were apparent in comparisons among ApoE E4 negative individuals in the FAD and healthy normal groups (P < 0.002). Our findings are consistent with the proposition that among ApoE E4 negative individuals HFE mutations are predisposing to FAD in males but are somewhat protective in females. Further, ApoE E4 effects in our FAD group are strongest in females lacking HFE mutations. Relative to younger normals there was a tendency for ApoE E4 and H63D to be overrepresented in males and underrepresented in females with DS. The possibility that HFE mutations are important new genetic risk factors for AD should be pursued further.

Adult↗
PubMed2000

Prevalence of dementia and impact on intellectual disability services.

In a statewide survey, dementia was found in 3% of adults age 40+; 6%, age 60+; and 12%, age 80+. Among adults with Down syndrome, the rates were 22% for adults age 40+ and 56% for adults age 60+. Observed onset occurred in the mid-60s (early 50s for those with Down syndrome). Alzheimer-type dementia was the most frequent diagnosis. With the occurrence of dementia expected to rise proportionately with the increase of longevity among adults with intellectual disabilities, care systems will have to raise the "index of suspicion" among staff and families, become "dementia capable," and improve their diagnostic and technical resources, as well as their care management supports designed to prolong the "aging in place" of adults affected by dementia.

Adult↗
PubMed1999

Increased levels of tau-like protein in patients with Down syndrome.

Tau-like protein levels from 40 Down syndrome (DS) persons (31-70 years old), 40 non-DS age-matched normal controls, 18 non-DS mentally retarded (MR) persons (26-91 years old), 25 probable Alzheimer disease (AD) patients (55-99 years old) and 24 non-demented elderly controls (54-79 years old) were measured using a sandwich enzyme linked immunosorbent assay. The levels were detected in 22 of 40 DS persons and were significantly higher in DS than any other group (P < 0.0001). There was no relationship between tau-like protein levels and age, gender or apolipoprotein E phenotypes in any of the five groups.

Adult↗
PubMed1998

Increased plasma amyloid beta protein 1-42 levels in Down syndrome.

Amyloid beta protein 1-40 (A beta40) and A beta42 levels were quantitated in plasma from 43 persons with Down syndrome (DS; 26-68 years of age), 43 age-matched normal controls, and 19 non-DS mentally retarded (MR) persons (26-91 years of age) by using a sandwich enzyme linked immunosorbent assay. A beta40 levels were higher in DS and MR than controls, but were similar between DS and MR groups. A beta42 levels were higher in DS than controls or MR persons. The ratios of A beta42/A beta40 were higher in DS than controls or MR persons. The findings are consistent with those seen in DS brains.

Adult↗
PubMed1993

Age-associated chromosome 21 loss in Down syndrome: possible relevance to mosaicism and Alzheimer disease.

We previously observed low level mosaicism (2-4% normal cells) in phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) in 29% of a small group of elderly persons with Down syndrome (DS). An analysis of cytogenetic data on 154 trisomy 21 cases (age 1 day to 68 years) showed that the proportion of diploid cells in such cultures significantly increased (P < 0.005) with advancing age. Thus, the "occult" mosaicism in PBL of the elderly persons with DS is likely due to the accumulation of cells that have lost a chromosome 21. A consequence of chromosome 21 loss could be uniparental disomy of the 2n cells, a factor that might have significant biological consequences if some chromosome 21 genes are imprinted. Loss of a chromosome 21 from trisomic cells might result in tissue-specific mosaicism and "classical" mosaicism in different age groups. Chromosome 21 loss might also be relevant to the development of Alzheimer-type dementia in DS and in the general population.

Adolescent↗
PubMed1993

Immunoglobulin G subclasses in older persons with Down syndrome.

IgG subclasses were measured in sera from 33 persons with Down syndrome (DS) (mean age 55 +/- 7 years) and 33 age- and sex-matched control individuals using a mouse monoclonal antibody based sandwich enzyme linked immunosorbent assay. Significantly higher levels of IgG1 and IgG3 and lower levels of IgG2 and IgG4 subclasses were found in the DS group compared to the control individuals. The higher levels of IgG1 and IgG3 subclasses found in DS persons were consistent with those seen in patients with autoimmune diseases and chronic viral infections; the lower levels of IgG2 and IgG4 subclasses were consistent with those seen in patients with recurrent infections. Our findings are similar to those reported in children with DS. We speculate that the subclass levels may have little or no relationship to the development of brain lesions typical of Alzheimer disease in older persons with DS. There were no significant differences between the levels of IgG subclasses of persons with DS showing signs of dementia of the Alzheimer type compared to those without such manifestations.

Adult↗
PubMed1992

Aluminium and the pathogenesis of Alzheimer's disease: a summary of evidence.

Known risk factors for Alzheimer's disease (AD) are few and insufficient knowledge is available to recommend steps to reduce AD in our ageing populations. Although not 'the cause', considerable evidence implicates human ingestion of aluminium as a possible risk factor for the expression of dementia of the Alzheimer type. A recent epidemiological study in Ontario relating the incidence of AD to aluminium in drinking water strongly supports this conclusion. To test further the hypothesis that aluminium may play a role in the pathogenesis of AD we conducted a clinical trial employing the trivalent metal ion binding compound, desferrioxamine. The design was a two-year randomized trial with behavioural assessments blinded to study assignment. Sixty-three patients with probable AD were selected who were living at home and were under 74 years. Forty-eight signed an informed consent and completed all initial testing. The main outcome measure was a video-recorded home-behavioural assessment of measures of skills of daily living. The principal outcome was that the mean slope for performance of the skills of daily living for the group without treatment was -1.72% maximum score/month, compared to -0.87% maximum score/month for the group treated with desferrioxamine (P = 0.038). Considerable evidence supports the hypothesis that aluminium has an active role in the pathogenesis of AD.

Aluminum↗
PubMed1992

Lessons from the United Kingdom: fightback on workplace hazards, 1979-1992.

For the past 13 years there has been an aggressive anti-union government in the United Kingdom. Yet despite this fact, very real advances have been made in the area of working-class activity over the issue of workplace hazards. Trade unions, because of membership concern and activity, have been forced to keep this topic on their agenda. The European Community has been a big factor in these advances. This article describes some of the issues and elements of the fightback. In the 1990s, with the rediscovery of environmental issues, the hazards movement of the United Kingdom, and elsewhere, is here to stay and set to expand.

Absenteeism↗
PubMed1991

Intramuscular desferrioxamine in patients with Alzheimer's disease.

Although epidemiological and biochemical evidence suggests that aluminium may be associated with Alzheimer's disease (AD), there is no convincing proof of a causal link for aluminium in disease progression. We have completed a two year, single-blind study to investigate whether the progression of dementia could be slowed by the trivalent ion chelator, desferrioxamine. 48 patients with probable AD were randomly assigned to receive desferrioxamine (125 mg intramuscularly twice daily, 5 days per week, for 24 months), oral placebo (lecithin), or no treatment. No significant differences in baseline measures of intelligence, memory, or speech ability existed between groups. Activities of daily living were assessed and videorecorded at 6, 12, 18, and 24 month intervals. There were no differences in the rate of deterioration of patients receiving either placebo or no treatment. Desferrioxamine treatment led to significant reduction in the rate of decline of daily living skills as assessed by both group means (p = 0.03) and variances (p less than 0.04). The mean rate of decline was twice as rapid for the no-treatment group. Appetite (n = 4) and weight (n = 1) loss were the only reported side-effects. We conclude that sustained administration of desferrioxamine may slow the clinical progression of the dementia associated with AD.

Aged↗
PubMed1990

Red cell superoxide dismutase, glutathione peroxidase and catalase in Down syndrome patients with and without manifestations of Alzheimer disease.

The activities of red blood cell enzymes that scavenge the superoxide radical and hydrogen peroxide were measured in severely to profoundly retarded adult Down syndrome (DS) patients with and without manifestations of Alzheimer disease (AD), and control individuals matched for sex, age, and time of blood sampling. Cu,Zn superoxide dismutase (SOD-1) and glutathione peroxidase (GSHPx) activities were significantly elevated (1.39-fold and 1.24-fold, respectively) in DS individuals without AD. When an adjustment was made for the SOD gene dosage effect, DS patients with AD manifestations had significantly lower SOD levels than the matched control individuals. In contrast, DS patients with and without AD had a similar elevation in GSHPx (an adaptive phenomenon). The mean catalase (CAT) activity was no different in DS and control individuals; however, in a paired regression analysis, DS patients without AD had marginally lower CAT activity than control individuals, whereas DS patients with AD had slightly but not significantly higher CAT activity. Thus, AD manifestations in this DS population are associated with changes in the red cell oxygen scavenging processes.

Adult↗
PubMed1990

Autoimmune thyroiditis associated with mild "subclinical" hypothyroidism in adults with Down syndrome: a comparison of patients with and without manifestations of Alzheimer disease.

Serum tests of thyroid function were compared in Down syndrome (DS) patients with and without manifestations of Alzheimer disease (AD). Relative to control individuals, DS patients had, overall, lower mean total T4 (P = 0.070) and T3f (P = 0.015), higher T3U (P = 0.013) and TSH (P = 0.020), no difference in free T4, and higher thyroid antithyroglobulin (ATA) (P = 0.033) and antimicrosomal autoantibody (AMA) titres (P = 0.0097). Similar trends were apparent in DS males and females, and in DS patients off all drugs. In an analysis of case/control pairs with corrections for age and sex, DS patients with AD manifestations (n = 9) had significantly lower T3 (P = 0.029) and higher AMA (P = 0.043) than paired control individuals, whereas DS patients without AD manifestations (n = 20) had significantly lower T3 (P = 0.013) but higher ATA (P = 0.0065). T3 was significantly lower in the DS patients with AD manifestations than in the unaffected (P = 0.0013). These data suggest that autoimmune thyroiditis associated with a mild "subclinical" form of hypothyroidism is common in adult DS patients and more pronounced in patients with AD manifestations than in those without. This "subclinical" hypothyroidism may contribute to cognitive deficits in ageing DS patients.

Adult↗
PubMed1986

Clinical expression of Alzheimer's disease in Down's syndrome.

Reports of the clinical manifestations of dementia in persons with Down's syndrome have been conflicting. Neuropathologic studies have been inconsistent with the clinical picture in many cases. Clarification of these issues requires longitudinal studies of patients combined with postmortem studies of brain tissue.

Adult↗
PubMed1985

Alzheimer's disease in Down's syndrome: clinicopathologic studies.

Clinical and neuropathologic evidence points to the development of Alzheimer's disease (AD) in seven Down's syndrome patients above age 40. Dementia was observed in these patients over periods of 2.5 to 9.2 years. The first clinical sign of AD, visual memory loss, was succeeded by impaired learning capacity and decreased occupational and social functioning, and culminated in seizures and urinary incontinence. The morphometric observations of the brains of these seven patients with AD showed that the numbers of plaques and tangles exceeded 20 per 1.5 X 10(6) microns2 area, in both the prefrontal and hippocampal cortices. Plaques and tangles were also evident in the basal ganglia, thalamus, hypothalamus, and midbrain. In addition, we found that four of the seven brains showed small strokes, and five of the seven amyloid angiopathy. This study also indicates that by longitudinal neuropsychological evaluations and lab tests, which exclude other causes of dementia, the diagnosis of AD can be made even in severely and profoundly retarded patients.

Adult↗