Rolf Adolfsson

Major depression in stroke patients. A 3-year longitudinal study.

Background and Purpose This prospective study was designed to examine the contributions of neurobiological, functional, and psychosocial factors to major depression after stroke. In addition, the prevalence and longitudinal course of major depression were studied. Methods Major depression, functional ability, and social network were assessed repeatedly for a period of 3 years in a population-based cohort of 80 patients with acute stroke (mean age, 73 years). Cerebral atrophy and brain lesion parameters were determined from computed tomographic scans performed acutely and after 3 years. Results The prevalence of major depression was 25% at the acute stage and approximately the same at 3 months (31%). It decreased to 16% at 12 months, was 19% at 2 years, and increased to 29% at 3 years. The most important predictors of immediate major depression were left anterior brain lesion, dysphasia, and living alone. Dependence in activities of daily living was the most important predictor at 3 months. From 12 months on, the patients having few social contacts outside the immediate family contributed most to depression, and at 3 years cerebral atrophy also contributed. At 1 year, 60% of the patients with early depression (0 to 3 months) had recovered; those not recovered at this follow-up had a high risk of development of chronic depression. Conclusions The study has provided evidence of a differentiation of factors likely to be implicated in the development of depression after stroke based on the period of time since the stroke event.

The betula prospective cohort study: Memory, health, and aging

Abstract The objective of this article is to present an overview of a prospective cohort study involving a total of 3,000 subjects whose ages were 35, 40, 45, 50, 55, 60, 65, 70, 75, and 80 years when first tested. the design of the study includes three waves of data collection. the first of these waves was conducted in 1988-1990, the second in 1993-1995, and the third will be conducted in 1998-2000. One sample of 1,000 subjects in these age cohorts underwent testing in 1988-1990 (100 subjects per cohort). This sample and two additional samples were tested in 1993-1995 and will be tested again in 1998-2000. Subjects take part in extensive health and memory examinations, and interviews about social factors. the memory testing covers a wide range of memory functions. the chief objectives of the study are to (a) examine the development of health and memory in adulthood and old age; (b) determine early preclinical signs of dementia; (c) determine risk factors for dementia; and (d) assess premorbid memory func...

Transmitter deficits in Alzheimer's disease

The pattern of neurotransmitter pathway losses in Alzheimers disease are reviewed. Deficits of the cholinergic pathway from the nucleus basalis, the noradrenergic pathway from the locus coeruleus and the serotoninergic pathway from the raphe nuclei are established. Cortical somatostatin interneurons are affected and dopaminergic neurons may be affected although these may be late or secondary phenomena in the disease process. Other neuronal systems, particularly in the hippocampus and temporal cortex, are also damaged. However, the disease is not one of generalised neuronal atrophy since some neurons are selectively spared. The established pathway-specific losses are discussed in relation to the clinical symptomatology and the pathology of the disorder. The biochemical and histological findings are compared with similar measurements made on tissues from other dementing disorders in an attempt to trace features common to dementias. Finally, as an addendum, a hypothesis is briefly outlined which attempts to explain the common features of the affected neurons and the pathogenesis of the disorder.

Circadian clock-related polymorphisms in seasonal affective disorder and their relevance to diurnal preference.

Disturbed circadian rhythms have been observed in seasonal affective disorder (SAD). The aim of this study was to further investigate this connection, and to test for potential association between polymorphisms in circadian clock-related genes and SAD, seasonality (seasonal variations in mood and behavior), or diurnal preference (morningness–eveningness tendencies). A total of 159 European SAD patients and 159 matched controls were included in the genetic analysis, and subsets were screened for seasonality (n=177) and diurnal preference (n=92). We found that diurnal preference was associated with both SAD and seasonality, supporting the hypothesis of a link between circadian rhythms and seasonal depression. The complete case–control material was genotyped for polymorphisms in the CLOCK, Period2, Period3, and NPAS2 genes. A significant difference between patients and controls was found for NPAS2 471 Leu/Ser (χ2=9.90, Bonferroni corrected P=0.035), indicating a recessive effect of the leucine allele on disease susceptibility (χ2=6.61, Bonferroni corrected P=0.050). Period3 647 Val/Gly was associated with self-reported morningness–eveningness scores (n=92, one-way ANOVA: F=4.99, Bonferroni corrected P=0.044), with higher scores found in individuals with at least one glycine allele (t=3.1, Bonferroni corrected P=0.013). A second, population-based sample of individuals selected for high (n=127) or low (n=98) degrees of seasonality, was also genotyped for NPAS2 471 Leu/Ser. There was no significant difference between these seasonality extreme groups, and none of the polymorphisms studied were associated with seasonality in the SAD case–control material (n=177). In conclusion, our results suggest involvement of circadian clock-related polymorphisms both in susceptibility to SAD and diurnal preference.

Biochemical changes in Dementia disorders of Alzheimer type (AD/SDAT)

In postmortem investigations of patients with dementia of Alzheimer type (AD/SDAT) (n = 14) the brain weight was significantly reduced when compared to controls (n = 16). In four AD/SDAT-brain parts investigated the concentrations of 5-hydroxy-tryptamine and noradrenaline were significantly reduced while 3-methoxy-4-hydroxyphenylglycol was significantly increased. In the caudate nucleus of the AD/SDAT-brains the concentrations of dopamine and homovanillic acid were significantly reduced. The activity of monoamine oxidase B was increased suggesting a proliferation of extra neuronal tissue in the AD/SDAT-brains. The activity of choline acetyl transferase was reduced in the four brain parts investigated, showing a general reduction in the acetylcholine system in the AD/SDAT-brains. The ganglioside concentration was significantly reduced suggesting a reduced density of nerve endings in the demented brains. The AD/SDAT-group was according to rating scales severely demented. Patients with an early onset of the dementia disease were more severely intellectually reduced and had more pronounced biochemical disturbances than those with a late onset of the dementia.

Histopathological criteria for progressive dementia disorders: clinical pathological correlation and classification by multivariate data analysis

SummaryAutopsied brains from 55 patients with dementia between 59–95 years of age (mean age 77.9±8.1 years) and 19 non-demented individuals between 46–91 years of age (mean age 74.3±10.5 years) were examined to establish histopathological criteria for normal ageing, primary degenerative [Alzheimers disease (AD)/senile dementia of Alzheimer type (SDAT)] and vascular (multi-infarct) dementia (MID) disorders. Senile/neuritic plaques, neurofibrillary tangles, microscopic infarcts and perivascular serum protein deposits were quantified in the frontal lobe (Brodmann area 10) and in the hippocampus. The demented patients were classified according to the DSM-III criteria into AD/SDAT and MID. Operationally defined histopathological criteria for dementias, based on the degree/amount of the histopathological changes seen in aged non-demented patients, were postulated. The demented patients were clearly separable into three histopathological types, namely AD/SDAT, MID and AD-MID, the dementia type where both the degenerative and the vascular changes are coexistent in greater extent than are seen in the non-demented individuals. Using general clinical, gross neuroanatomical and histopathological data three separate dementia classes, namely AD/SDAT, MID and AD-MID, were visualized in two-dimensional space by multivariate data analysis. This analysis revealed that the pathology in the AD-MID patients was not merely a linear combination of the pathology in AD/SDAT and MID, indicating that AD-MID might represent a dementia type of its own. The clinical diagnosis for AD/SDAT and MID was certain in only half of the AD/SDAT and one third of the MID cases when evaluated histopathologically and by multivariate data analysis. AD/SDAT, MID and AD-MID were histopathologically diagnosed in 49%, 24% and 27%, respectively, of all the dementia cases studied. Opposite correlation between the number of tangles, plaques and the patient age in non-demented and AD/SDAT cases were observed, indicating that the pathogenesis of tangles and plaques in the two groups of patients might be different and that AD/SDAT might not be a form of an exaggerated ageing process.

Increased activity of brain and platelet monoamine oxidase in dementia of Alzheimer type

Abstract Two groups of patients with dementia of Alzheimer type were studied with respect to monoamine oxidase (MAO) activity. In one group of 11 patients MAO activity was determined in platelets and in the other group of 14 patients in the brain (hypothalamus, caudate nucleus, hippocampus and cortex gyrus cinguli) post mortem. The results were compared to controls matched for age and sex. Platelet MAO activity was significantly higher in patients with dementia of Alzheimer type compared to controls. Brain MAO-B activity but not MAO-A activity was significantly higher in the dementia group in hyppocampus and cortex gyrus cinguli. In the controls there were positive correlations for MAO-B activity with age in the four brain regions, but these correlations were absent in the dementia group. This could be explained by differences in age of onset of dementia and that the disease process does not develop homogeneously in different brains.

Post-mortem distribution of dopamine and homo-vanillic acid in human brain, variations related to age, and a review of the literature

The post-mortem brain concentrations of dopamine (DA) and homo-vanillic acid (HVA) were determined in 16 parts of the brain from patients with no history of neurologic or psychiatric illness. Fifteen men and nine women, with a mean age of 61.0±18.7 years (range 23–92 years) were included. They had died from either ischaemic heart disease or cancer. In the post-mortem investigation several factors were controlled: age, time between death and autopsy, time between autopsy and chemical analysis and storage time (−20 °C). The DA concentrations in the different brain areas were found to be positively intercorrelated, especially those in the basal ganglia, hippocampus and the mesencephalon. The HVA concentrations measured in various cortical structures were also positively intercorrelated. In several regions of the brain there was a significant inverse correlation between the DA and HVA concentrations. The DA and HVA concentrations did not differ according to sex, but age had a marked influence on the DA concentration. Significant decrease with age was observed in the nucleus caudatus, globus pallidus, mesencephalon, hippocampus and in the cortex gyrus hippocampus. These findings are discussed in relation to the effect of aging neurons. A review of human post-mortem investigations on DA and HVA concentrations is also presented.

Nutritional status and dietary intake in institutionalized patients with Alzheimer's disease and multiinfarct dementia.

Nutritional status, dietary intake, weight change, and mortality were studied in a sample of severely demented, institutionalized patients. Dietary intake was registered during five days in two periods, five weeks apart. A weighing method was used. Nutritional status was assessed by anthropometric measurements (weight for height index, triceps skinfold thickness, arm muscle circumference) and determination of circulating proteins (albumin, transferrin, and prealbumin).

Three circadian clock genes Per2, Arnt1, and Npas2 contribute to winter depression

Background. Multiple lines of evidence suggest that the circadian clock contributes to the pathogenesis of winter depression or seasonal affective disorder (SAD). We hypothesized that sequence variations in three genes, including Per2, Arntl, and Npas2, which form a functional unit at the core of the circadian clock, predispose to winter depression. Methods. In silico analysis of the biological effects of allelic differences suggested the target single‐nucleotide polymorphisms (SNPs) to be analyzed in a sample of 189 patients and 189 matched controls. The most relevant SNP in each gene was identified for the interaction analysis and included in the multivariate assessment of the combined effects of all three SNPs on the disease risk. Results. SAD was associated with variations in each of the three genes in gene‐wise logistic regression analysis. In combination analysis of variations of Per2, Arntl, and Npas2, we found additive effects and identified a genetic risk profile for the disorder. Carriers of the risk genotype combination had the odds ratio of 4.43 of developing SAD as compared with the remaining genotypes, and of 10.67 as compared with the most protective genotype combination. Conclusion. Variations in the three circadian clock genes Per2, Arntl, and Npas2 are associated with the disease, supporting the hypothesis that the circadian clock mechanisms contribute to winter depression.