A profile of the burdens of care of Alzheimer's disease patients.
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Aged↗
Biomedical subjects
B Winblad
Publications and source records attributed to B Winblad.
Assessing the societal impact of acetylcholinesterase inhibitor therapies.
The symptomatology of Alzheimer disease (AD), its longevity, and associated cost make it an extremely challenging disease for individuals, their families, health care, and social support systems. Moreover, the expanding aging population worldwide means that strategies to contain costs are an urgent priority. As the largest component of the direct costs of AD is due to the cost of institutionalization, cost-containment strategies have focused on ways to maintain the AD patient in the community for as long as possible. Disease severity is a strong predictor of institutionalization, and patients' cognitive function (in the form of their Mini-Mental State Examination score) is frequently used as a prognostication of their living environment, and thus the overall cost of their care. Strategies to maintain patients at home are directed at either the patient's symptoms or the caregiver's ability to cope with those symptoms and the responsibilities of caregiving. Examples of strategies directed at the caregiver include education and support programs. Drug treatments, notably acetylcholinesterase inhibitors, present the best option for improving patient function, thereby preserving patient autonomy. A number of preliminary studies, whose results are summarized here, have demonstrated that the use of the acetylcholinesterase inhibitors tacrine, metrifonate and donepezil, and the glial cell modulator, propentofylline, results in reductions in the overall costs of care. Most health economic studies have focused only on comparison of the costs associated with paying for administering a treatment and the savings produced by postponed institutionalization. However, there is a growing realization that some measures of the quality of life or well-being of both patient and caregiver should also be incorporated. Thus, the health economics of dementia is an extremely complex area of study that is rapidly growing, due to the likelihood that cost-effectiveness will form the basis for future reimbursement decisions.
Alzheimer Disease↗
Quality of life among the elderly. State of mood and loneliness in two selected groups.
Cognitively impaired and intact elderly subjects from a longitudinal project were interviewed in a follow-up study about their present state of mood and how often they experienced loneliness. In all, 315 subjects were involved in the study. The dropout rate was high, about 50%, due to death and to the fact that some elderly persons--especially those with slightly impaired cognitive function--declined to participate. The present state of mood was measured by the Geriatric Depression Scale and loneliness was assessed by the question, 'Do you experience loneliness often, sometimes, seldom or never?' Most subjects (4 out of 5), above all those who were cognitively intact, reported basic satisfaction with their lives. The greatest difference in response between the two cognitive groups was found in the question about having an empty life. Loneliness and sad mood prevailed especially among subjects with cognitive difficulties. In summary, experiencing loneliness had a negative influence on the state of mood in both cognitive groups, particularly among persons with cognitive impairment.
Affect↗
Cognitive impairment, drug use, and the risk of hip fracture in persons over 75 years old: a community-based prospective study.
The authors examined the effects of cognitive function, as assessed by the Mini-Mental State Examination, and drug use on the incidence of hip fracture in a community-based Swedish population of 1,608 subjects who were aged > or = 75 years on October 1, 1987, and who had not had a hip fracture. During the 7,123.8 person-year follow-up, 134 first hip fractures were identified. The Cox proportional hazards model was used to estimate the relative risk of developing hip fracture, taking into account several potential confounders. Compared with those without cognitive impairment, subjects with mild impairment (Mini-Mental State Examination scores 18-23) had a relative risk of 2.04 (95% confidence interval (CI) 1.29-3.24), and subjects with moderate-severe impairment (Mini-Mental State Examination score < 18) had a relative risk of 2.09 (95% CI 1.17-3.72). Subjects using opioid analgesics (97% took propoxyphene) had a relative risk of 2.01 (95% CI 1.19-3.40). Taking potassium supplements (99% took potassium chloride) was related to a reduced risk of hip fracture (relative risk = 0.55, 95% CI 0.31-0.98), while diuretics did not have an independent impact. In summary, the results show that cognitive impairment and use of propoxyphene are associated with increased risk of hip fracture. The observed protection of potassium chloride merits further attention. The limitation of the study was that the assessment of drug use was made only at baseline.
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Alzheimer changes are common in aged drivers killed in single car crashes and at intersections.
With increasing age, diseases affecting the cognitive functions are more frequent. These diseases may increase the risk for fatal car crashes. We analyzed the frequency of neuropathological alterations characteristic of Alzheimer's disease (i.e. neuritic and diffuse plaques, and neurofibrillary tangles) in two association areas of the brain, parietal and frontal cerebral cortex, from 98 fatally injured aged drivers. In the age groups of 65-75 and over 75 years of age, 50% and 72% of the drivers, respectively, had neuritic plaques in either parietal and/or frontal cortex. In 14% of all killed drivers the number of neuritic plaques reached the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) age-related histologic score C, which indicates the diagnosis of Alzheimer's disease (AD), and an additional 33% had score B, which suggests the diagnosis of AD. Neuropathological AD changes were most common in the brains of drivers killed in single vehicle crashes, followed by multivehicle crashes at intersections and least common in multivehicle crashes elsewhere, but the differences did not reach statistical significance. In a great majority (80-85%) of cases the killed aged driver was the guilty party of the crash. The results imply, that incipient AD may contribute to fatal crashes of aged drivers, and therefore the forensic autopsy of these victims should include neuropathological examination.
Accidents, Traffic↗
Longitudinal changes in quantitative EEG during long-term tacrine treatment of patients with Alzheimer's disease.
Quantitative EEG is a potentially useful tool in demonstrating the effects of treatments with acetylcholinesterase (AChE) inhibitors on the progression of Alzheimer's disease (AD). In order to define the profile of EEG changes during tacrine long-term treatment, for 12 months we followed 15 AD patients receiving an optimal individually tolerable dose. After 3 months theta global field power (GFP) was significantly reduced, and after 6 months both theta and delta GFP decreased. Theta GFP was still reduced after 12 months of treatment when compared to the baseline. Significant decreases in fast activities of beta 1 and beta 2 GFP were also observed. The untreated reference group (n = 10) did not show any significant changes in GFP after 12 months follow-up, although generators of theta activity had a significant shift towards posterior regions. These findings suggest that slowing in fast EEG frequencies during chronic treatment with AChE inhibitors may provide an early indicator of declining treatment efficiency.
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Enhanced localization of amyloid beta precursor protein in the rat hippocampus following long-term adrenalectomy.
Using various antibodies to the amyloid ss precursor protein (APP) associated with Alzheimer's disease, we investigated changes in the distribution of APP in the hippocampus and neocortex of adrenalectomized (ADX) rats. In contrast to sham-operated controls, ADX rats euthanised after a survival period of 5 months showed striking APP reactivity in the CA1-CA4 fields and in the surviving cells in the dentate gyrus. Our results suggest the enhanced APP reactivity in hippocampal neurons may pertain to previous observations on the accumulation of APP fragments in the neocortex during ischemic or traumatic injury. Thus, long-term hormone deprivation would be another factor, which may influence the expression of APP in brain.
Adrenalectomy↗
Psychotic symptoms and apolipoprotein E genotypes in an elderly population.
BACKGROUND: Psychotic symptoms have been found to be more common in demented elderly persons. Genetic variation in the apolipoprotein E (APOE) gene is reported to be associated with variation in the risk of Alzheimer's dementia. This study reports on variables associated with psychotic symptoms including APOE, in demented and nondemented elderly persons. METHODS: A population of 668 elderly persons was examined. APOE genotype was available in 309 individuals. RESULTS: Psychotic symptoms were found to be associated with dementia, a previous psychiatric history, female gender, being less educated, disability in daily living and institutionalisation. In the nondemented group, psychotic symptoms were equally common in subjects with or without the epsilon 4 present. In the demented subjects, psychotic symptoms were slightly more common, although not significant, in subjects without the epsilon 4 genotype. CONCLUSIONS: There was no statistical significant difference in APOE genotype between subjects with and without psychotic symptoms, stratified by dementic diagnosis.
Activities of Daily Living↗
Kainic acid induced expression of interleukin-1 receptor antagonist mRNA in the rat brain.
The endogenous interleukin-1 receptor antagonist (IL-1ra), a protein with partial homology with the proinflammatory cytokine interleukin-1beta (IL-1beta), prevents binding of IL-1beta to the signalling receptor. Exogenous IL-1ra has been shown to reduce the neuronal damage occurring after excitotoxic amino acid administration and ischemia. In the present study, in situ hybridization histochemistry was employed to investigate the regulation of endogenous IL-1ra mRNA expression in the rat brain after peripheral administration of kainic acid (10 mg/kg). IL-1ra mRNA expression was markedly induced in the hippocampus, thalamus, amygdala, piriform cortex, perirhinal cortex, entorhinal cortex, and to a lesser extent in the hypothalamus, and parietal and temporal cortex. The expression was first detected at 5 h after the kainic acid administration and it was markedly increased at 24 h. No signal was detected at 4 days after the injection. The majority of the cells expressing IL-1ra mRNA displayed the morphological characteristics of microglia. Expression of IL-1ra mRNA in neurons occurred mainly in the piriform and perirhinal cortex. The distribution pattern of IL-1ra mRNA expressing microglia-like cells was similar to that of cells labelled with ED1, a marker for activated microglia. The induction of IL-1ra mRNA expression may represent an endogenous response to balance IL-1 receptor mediated activity in the brain following kainic acid administration, conceivably to elicit neuroprotective and/or antiinflammatory effects.
Animals↗
Accumulation of cyclin-dependent kinase 5 (cdk5) in neurons with early stages of Alzheimer's disease neurofibrillary degeneration.
Cyclin-dependent kinase 5 (cdk5) is one of the candidate kinases involved in the abnormal hyperphosphorylation of tau. To have a direct effect on tau hyperphosphorylation, cdk5 protein levels and enzyme activity should be upregulated in especially those neurons that develop neurofibrillary tangles (NFTs). We studied the distribution of cdk5 immunoreactivity in neurons with or without early- and late-stage NFTs in hippocampal, entorhinal, transentorhinal, temporal and frontal cortices, and cerebellum of Alzheimer's disease (AD) and control brain. The immunocytochemical localisation of cdk5 was compared with that obtained using antibodies to PHF-tau (tau in paired helical filaments of NFTs, mAb AT8) and ubiquitin as markers of early and late stage NFTs, respectively. Immunoreactivities of cdk5 and PHF-tau were found in neuronal perikarya and processes of hippocampal, entorhinal, transentorhinal, temporal and frontal, and cerebellar cortices. An apparent increase of cdk5 immunoreactivity was seen in pretangle neurons and in neurons bearing early stage NFTs. These findings suggest that this kinase might be involved in the formation of NFTs at a relatively early stage in the neocortex.
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Changes in IGF-1 receptors in the hippocampus of adult rats after long-term adrenalectomy: receptor autoradiography and in situ hybridization histochemistry.
Alteration of insulin-like growth factor-1 (IGF-1) receptor and its mRNA after long-term adrenalectomy (ADX) was studied in the hippocampus by in vitro receptor autoradiography and in situ hybridization histochemistry, respectively. Significantly, decreased levels of IGF-1 receptor and its mRNA was noted in the dentate and CA1-CA4 regions of the hippocampus of the ADX animals, suggesting that the level and expression of IGF-1 receptors in the hippocampus is influenced by adrenal hormones.
Adrenal Cortex Hormones↗
Long-term adrenalectomy decreases NMDA receptors in rat hippocampus.
The effect of long-term adrenalectomy on NMDA receptors in the rat hippocampus was studied. Hippocampal sections of control and adrenalectomized rats were incubated with [3H]MK-801, a radiolabeled non-competitive inhibitor of the NMDA receptor. Analysis by in vitro autoradiography showed a significant decrease in [3H]MK-801 binding in the dentate gyrus, CA1 and CA4 areas, as well as the temporal cortex. Results of this study suggest that glucocorticoids are vital for the regulation of the NMDA receptors.
Adrenal Glands↗
Loss of inositol 1,4,5-trisphosphate receptor sites and decreased PKC levels correlate with staging of Alzheimer's disease neurofibrillary pathology.
Inositol 1,4,5-trisphosphate (IP3), inositol 1,3,4,5-tetrakisphosphate (IP4) and protein kinase C (PKC) play important roles in the phosphoinositide hydrolysis signal transducing pathway. Several studies have shown severe deficits in both IP3 receptor levels and PKC levels and activity in Alzheimer's disease brain, although the relationship of these changes to disease pathology is poorly understood. In the present study, we determined the autoradiographic localization of [3H]IP3 and [3H]IP4 binding to their calcium mobilizing receptor sites and [3H]phorbol 12,13-dibutyrate ([3H]PDBu) binding to PKC in sections of entorhinal cortex/hippocampal formation and cerebellum from 24 cases that had been staged for Alzheimer's disease-related neurofibrillary changes and amyloid deposition according to Braak and Braak [Acta Neuropathol. Berl., 82 (1991) 239-259]. Results indicated that [3H]IP3 binding showed a trend towards a decline with staging for neurofibrillary changes in the entorhinal region (0.05 < P < 0.10, ANOVA) and subiculum (0.05 < P < 0.10). In the former region, [3H]IP3 binding showed a significant decline with staging for amyloid deposition (P < 0.05). [3H]IP3 binding in the CA1 region showed statistically significant declines with respect to both neurofibrillary changes and amyloid staging (P < 0.05). [3H]IP3 binding levels in the other hippocampal subregions were too low to quantify accurately. The binding of [3H]IP4 showed no significant changes with either neurofibrillary changes or amyloid staging in any of the regions investigated. In contrast, [3H]PDBu binding showed significant declines with neurofibrillary staging in the entorhinal region (P < 0.01), subiculum (P < 0.001), CA1 (P < 0.001), CA2 (P < 0.001), CA3 (P < 0.001) and CA4 (P < 0.0001) regions and the dentate gyrus (P < 0.0001). Of these regions, only the subiculum showed a significant decline of [3H]PDBu binding with amyloid staging. There were no significant neurofibrillary or amyloid stage-related changes in either [3H]IP3, [3H]IP4 or [3H]PDBu binding in the molecular layer of the cerebellum. These findings suggest that reduced IP3 receptor and PKC levels in the entorhinal cortex/hippocampal formation reflect and may be important for the progression of Alzheimer's disease neurofibrillary pathology. The data also suggests that hippocampal IP3 receptor loss is related to the extent of amyloid deposition.
Adult↗
[Genetic factors are often found inl Alzheimer disease. An extensive twin study to clarify the heredity-environment relationship].
Genetic and environmental risk factors are central concerns in dementia research. Through twin studies one can study the relative importance of genetic and environmental risk factors. One such study, based on the Swedish Twin Registry, shows that genetic effects are of considerable importance for developing Alzheimer's disease, even late in life, but that environmental factors are also important. For vascular dementia, the results indicate that non-genetic factors are of primary importance.
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EEG slowing and cerebrospinal fluid tau levels in patients with cognitive decline.
We explored the relationship between cerebrospinal fluid (CSF) tau levels as indirect markers of tau-related pathology in Alzheimer's disease (AD) and EEG slowing, a typical neurophysiological finding in the disease. A positive correlation between CSF tau levels and ratio of alpha/delta global field power was found in 14 AD patients (r = 0.65, p = 0.01). This relationship was better approximated by polynomial fit of 2nd degree (p = 0.002). A subgroup of AD patients (n = 7) with higher tau levels and shorter duration of illness showed a strong relationship between CSF tau levels and alpha/theta (r = 0.83, p = 0.02), and alpha/delta (r = 0.87, p = 0.01) ratios of the global field power. There were no significant correlations between EEG slowing and CSF tau levels in 12 patients with mild cognitive dysfunction or in 14 healthy control subjects. That a strong inverse linear correlation exists in AD patients with higher levels of tau and shorter duration of illness may imply that with longer illness duration CSF tau levels decrease due to neuronal death.
Aged↗
Feelings of anxiety and associated variables in a very elderly population.
OBJECTIVE: Anxiety disorders have been reported to decrease with age, while anxiety feelings have been reported to be as common as in younger age groups. In order to further explore this relationship and variables associated with anxiety, a population of very elderly persons was examined. METHODS: 966 persons, aged 78 years and over, underwent an examination by a physician including a structured psychiatric interview. RESULTS: Anxiety feelings are strongly associated with psychiatric disturbances (anxiety disorders and depressive disorders). Moreover, the feelings were associated with dementia, a history of psychiatric disorders (most often depression), being female and being dissatisfied with social network. Few of those with a psychiatric disorder were adequately treated, in spite of the fact that most of them had seen a physician during the past month. CONCLUSIONS: After excluding an anxiety disorder, one of the most important things to consider in a very old person with anxiety is whether depression is present or not. Generally, there is a need for more education of physicians concerning the common mental disorders in the elderly in order to improve their management.
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The Circle Model--support for relatives of people with dementia.
Home care for cognitively impaired elderly puts tremendous stress and burden on their families. Therefore it is important to search for effective care models in order to provide support for this group. In this study, an intervention model--the Circle Model--was developed, tested and evaluated in six places in Sweden. The model is unique in that family caregivers and volunteers were trained together in study circles. After their training, the volunteers replaced the caregivers in the homes on a regular basis, which permitted the caregivers some relief from the demands of caregiving. Interviews were conducted with the participants to gather information about their training and relief care experiences. The caregivers reported that the study circle provided opportunity to exchange experiences with other people in similar situations. They felt a spirit of community with other relatives, and were able to increase their knowledge in care providing and coping strategies. The emphasis in temporary relief care by the volunteers was placed on providing the relatives with feelings of security and relaxation. The satisfaction among the Circle Model participants was reciprocal. The volunteers also reported high satisfaction and appreciation of the knowledge which they acquired from the caregivers. The Circle Model brings new dimensions to the home care situation and should be seen as a complement to social services support.
Adaptation, Psychological↗
Natural history of Alzheimer's disease and other dementias: review of the literature in the light of the findings from the Kungsholmen Project.
The elderly population is increasing more than any other sector of the population. Dementia, a prevalent condition in the elderly, increases disability, morbidity and mortality among older people. For these reasons the possibility of predicting progression and prognosis has enormous importance. Despite the fact that dementia has gained widespread recognition in the past few decades, the knowledge of its natural history, in terms of progression and prognosis are not yet completely understood. However, thanks to longitudinal research, which has only recently begun to proliferate, not only is better comprehension of the continuity of the cognitive decline possible, but also the identification of some prognostic factors.
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