Dementia with Lewy bodies - a clinical and neurological approach

Dementia with Lewy bodies (DLB) is a dementia disorder, clinically characterized by fluctuating cognitive impairment, attention deficits, visual hallucinations, parkinsonism and other neuropsychiatric features. Sensitivity to neuroleptic medication is a common finding. In the present study 24% of 200 autopsied cases, within the Lund longitudinal prospective dementia study fulfilled the clinical diagnostic criteria of DLB. Compared to clinical Alzheimer (AD) cases, these cases also showed clinical signs of frontal dysfunction. Furthermore they had a greater degree of deterioration of dementia and were more reliant on outside assistance when compared to clinical AD cases. The blood pressure decreased during dementia and many cases became hypotensive and orthostatic. The pharmacological load was heavier in clinical DLB compared to AD. The neuropathological results revealed Lewy bodies in 38% of the clinically defined DLB cases. These cases also had other pathological changes such as Alzheimer pathology, vascular pathology and a degeneration of dopaminergic and cholinergic nuclei, eg substantia nigra and nucleus basalis Meynert. Clinical DLB cases lacking Lewy bodies were characterised by Alzheimer pathology combined with frontally selective incomplete white matter infarcts. EEG and regional cerebral blood flow measurements were not helpful in distinguishing between AD and DLB or in separating cases with Lewy body pathology from those without. When individual cases were analysed clinico-pathologically, the DLB symptoms could often be explained by the combinations of pathologies. The study illustrates the difficulties of the clinical recognition of a specific pathological entity in individuals and the complex relation between brain pathology, clinical symptoms, medication and its adverse effects

Measuring the noticing of an unexpected event in Magical Garden with a Teachable Agent using Eye-Tracking

Scientific views on what children are capable of have been revised through history again and again, usually when new methods of studying children’s capabilities are presented. What has often been concluded is that children are capable of more than what was previously thought. New technology has introduced a genre of educational games which utilize the captivating power of computer games which have shown a positive effect on learning and motivation. In this study, the educational game Magical Garden was used as a platform to train, teach, and test number sense. The pedagogical instrument Teachable Agent (TA) is a part of Magical Garden’s design which utilizes the protégé effect. A new method of measuring number sense, detecting an “unexpected event” by attending to it, is pro-posed and tested. The unexpected event was a tree elevator malfunction. The purpose of the unexpected event was to create a task where only the children who were attentive and knew which branch the elevator would go to would react to and detect the unexpected event. A model of detection of the unexpected event, looking back at the correct branch after the elevator passed the correct one, was proposed. Eye-tracking was used as the method of capturing detections of the unexpected event, as well as measuring the interaction between the children and the TA during the unexpected event. In this study, 42 preschoolers participated. The results show that children attend the TA significantly more when the TA was in charge of the decisions in the game. This indicates that preschoolers understand that the TA was in charge. The model of detection used in this study was not comprehensive. However, detecting an unexpected event could still be a promising method of measuring number sense. Therefore, future research could utilize this method to unveil more exciting capabilities of children with a more inclusive model of detection.Vetenskapliga synsätt på vad barn kan är kapabla till att klara av har reviderats om och om igen genom historien, oftast i samband med att nya metoder som undersöker barns förmågor uppkommit. Barn verkar gång på gång klara av mer än vad man tidigare hade trott. Lärspel utnyttjar datorspelens fängslande kraft, och har visat ha en positiv effekt för lärande och motivationen. I denna uppsats, kommer lärspelet Magical Garden användas som plattform för att träna, lära ut och testa förskolebarns taluppfattning. Det pedagogiska instrumentet Teachable Agent (TA) är en intrikat del av Magical Gardens design som försöker facilitera "protégé effect". I denna uppsats introduceras och testas en ny metod för att mäta taluppfattning, upptäcka en oväntad händelse genom att rikta uppmärksamhet mot händelsen. Den oväntade händelsen i spelet är att korghissen i ett träd åker fel. Den oväntade händelsen är utformad så att endast barn med tillräckligt god taluppfattning förstår att hissen åker till fel våning och kan uppmärksamma att hissen åker fel. Den modell som föreslogs var att barnen skulle uppmärksamma den korrekta våningen som hissen skulle stannat vid när de hade upptäckt att hissen åkte fel. En ögonrörelsekamera användes för att fånga upptäckterna och även för att mäta interaktionen mellan TA och barnen. Ett ögonrörelseexperiment utfördes på 42 förskolebarn på respektives förskola. Resultaten visade att barnen tittade i större utsträckning på TA när TAn styrde i spelet. En slutsats som kan dras från detta resultat är att förskolebarnen verkade förstå att det var TA som styrde när den styrde. Modellen för att upptäcka den oväntade händelsen var inte heltäckande. Men att upptäcka något oväntat kan fortfarande vara en lovande metod för att mäta taluppfattning. Därför borde framtida forskning använda denna metod för att avslöja fler förmågor hos barn och skapa en mer inkluderande modell för vad en upptäckt av något oväntat kan vara

The interaction effect of sex and apolipoprotein E genotype in Alzheimer’s disease—rates of progression and prognosis.

Objectives: To investigate the interaction effect of sex and apolipoprotein E (APOE) genotype on long-term cognitive and functional outcomes and survival in Alzheimer’s disease (AD). Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicentre study in clinical practice involving 999 participants diagnosed with mild-to-moderate AD at the start of cholinesterase inhibitor treatment (time of diagnosis). The patients were evaluated using Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS–cog), Instrumental Activities of Daily Living scale (IADL) and Physical Self-Maintenance Scale (PSMS) at baseline and semi-annually over 3 years, and date of death was recorded for 20 years. Results: The frequency of APOE ε4-carriers differed between sexes, 60% of males and 73% of females had 1 or 2 alleles (p < 0.001). The ε4-carriers were younger than non-ε4-carriers at the estimated onset of AD and at diagnosis in both sexes, and younger at death in males. After 3 years, decline in ADAS–cog was faster in both female APOE ε4-carriers, mean (95% confidence interval), 8.2 (6.5–9.8) and non-ε4-carriers 9.4 (6.4–12.3) points, than in male non-ε4-carriers 3.8 (0.9–6.7) points, (p = 0.036). Functional deterioration was faster in female non-ε4-carriers than in male non-ε4-carriers, IADL: 8.1 (6.8–9.4) vs. 4.9 (3.6–6.2) points (p = 0.007), and PSMS: 3.8 (3.0–4.7) vs. 2.2 (1.3–3.0) points (p = 0.033). These differences were not detected among ε4-carriers. Conclusions: The effect of APOE genotype differed between sexes in AD. Male ε4-carriers showed 2 years earlier death than male non-ε4-carriers. Female non-ε4-carriers demonstrated worse cognitive and functional prognosis than male non-ε4-carriers

In situ trap parameter studies in CCDs for space applications

Charge-Coupled Devices are the detector of choice for the focal planes of many optical and X-ray space telescopes. In recent years, EM-CCDs, SCDs and CMOS sensors have been used, or baselined, for missions in which the detection of X-ray and visible photons are key to the science goals of the mission. When placed in orbit, silicon-based detectors will suffer radiation damage as a consequence of the harsh space radiation environment, creating traps in the silicon. The radiation-induced traps will capture and release signal electrons, effectively “smearing” the image. Without correction, this smearing of the image would have major consequences on the science goals of the missions. Fitting to observed results, through careful planning of observation strategies while the radiation dose received remains low in the early stages of the mission, has previously been used to correct against the radiation damage effects. As the science goals becoming increasingly demanding, however, the correction algorithms require greater accuracy and a more physical approach is required, removing the effects of the radiation damage by modelling the trap capture and release mechanisms to a high level of detail. The drive for increasingly accurate trap parameters has led to the development of new methods of characterisation of traps in the silicon, measuring the trap properties and their effects to the single-trap level in situ. Here, we summarise the latest developments in trap characterisation techniques for n-channel and p-channel devices

Solitary living in Alzheimer's disease over 3 years: association between cognitive and functional impairment and community-based services.

Introduction: Many individuals with Alzheimer’s disease (AD) live alone, and this figure is expected to increase. This study aimed to describe the cognitive and functional abilities of solitary-living AD patients, and the potential predictors of their usage of community-based services. Methods: This 3-year, prospective, multicenter study included 1,021 participants with mild-to-moderate AD (Mini-Mental State Examination score, 10–26) treated with cholinesterase inhibitors (ChEI) in a routine clinical setting. At the baseline and every 6 months, patients were assessed using cognitive, instrumental and basic activities of daily living (ADL) scales, and service utilization was recorded. Logistic regression models were used to predict the usage of community-based services. Results: At the start of ChEI therapy (time of AD diagnosis), 355 individuals (35%) were living alone. They were mainly female, older, had more impaired basic ADL capacity, and a larger number of concomitant medications compared with those living with family. Regarding the solitary-living patients, lower instrumental ADL (IADL) ability and more medications were independent predictors of usage of home-help services, whereas more impaired IADL at baseline and faster IADL deterioration were predictors of nursing-home admission. For those living with family, older age, lower basic ADL, and a greater number of medications predicted home-help services, whereas a larger amount of home help predicted nursing-home placement. In addition, female sex was a risk factor for both the utilization of home-help services and nursing-home placement. Cognitive ability was not significantly associated with usage of community-based services. Conclusions: A large number of AD patients, predominantly females, live alone with severe cognitive and functional impairment. The amount of home-help services used did not reflect cognitive severity, suggesting that home help did not meet the needs related to cognitive deterioration. Increased knowledge of how community-based services can better accommodate the care needs of solitary-living individuals with AD is essential

5' Guanylylimidodiphosphate, a potent activator of adenylate cyclase systems in eukaryotic cells

5' Guanylylimidodiphosphate (Gpp(NH)p) stimulates adenylate cyclase [ATP pyrophosphate lyase (cyclizing), EC 4.6.1.1] activity in plasma membranes isolated from frog and salmon erythrocytes, from rat adrenal, hepatic, and fat cells, and from bovine thyroid cells. The nucleotide acts cooperatively with the various hormones (glucagon, secretin, ACTH, thyrotropin, and catecholamines) that stimulate these adenylate cyclase systems with resultant activities that equal or exceed those obtained with hormone plus GTP or with fluoride ion. In the absence of hormones, Gpp(NH)p is a considerably more effective activator than GTP, and, under certain conditions of incubation, stimulates rat fat cell adenylate cyclase to levels of activity (about 20 nmoles of 3',5' adenosine monophosphate mg protein per min) far higher than reported hitherto for any adenylate cyclase system examined. The nucleotide activates frog erythrocyte adenylate cyclase when the catecholamine receptor is blocked by the competitive antagonist, propranolol, and activates the enzyme from an adrenal tumor cell line which lacks functional ACTH receptors. In contrast, Gpp(NH)p does not stimulate adenylate cyclase in extracts from Escherichia coli B. Gpp(NH)p appears to be a useful probe for investigating the mechanism of hormone and nucleotide action on adenylate cyclase systems in eukaryotic cells.published_or_final_versio

The effect of functional capacity and concomitant medications on life expectancy in Alzheimer’s disease.

Background: An increased knowledge of predictors that might affect survival in Alzheimer’s disease (AD) patients treated with cholinesterase inhibitors (ChEIs) is important for clinicians and for the health services. Impairment in activities of daily living (ADL), somatic diseases, and psychiatric symptoms may influence mortality in AD. We aimed to study the impact of functional capacity and concomitant medications on patient life expectancy in clinical practice. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicenter study for the long-term assessment of ChEI treatment. This study included 791 deceased participants with a clinical diagnosis of mild-to-moderate AD (Mini-Mental State Examination score, 10–26) at the start of ChEI therapy (shortly after diagnosis). Patients were evaluated regarding cognitive and functional abilities and concomitant medications. The date of death was recorded. Survival was compared individually with that of the sex- and age-matched general population. Results: The mean ± SD time from AD diagnosis to death was 5.7 ± 2.8 years and varied among patients with different levels of instrumental ADL (IADL) impairment at baseline, from 6.6 ± 2.8 years (IADL score, 8–12) to 5.0 ± 2.5 years (IADL score, 21–31) (P < 0.001). The time from AD diagnosis to death also differed between patients receiving antihypertensive/cardiac therapy (no/yes, 6.1 ± 2.7 vs 5.3 ± 2.8 years; P < 0.001), antidiabetics (no/yes, 5.8 ± 2.8 vs 4.1 ± 2.4 years; P < 0.001), nonsteroidal anti-inflammatory drugs (NSAIDs)/acetylsalicylic acid; no/yes, 6.0 ± 2.8 vs 5.2 ± 2.6 years; P < 0.001), and antipsychotics (no/yes, 5.8 ± 2.8 vs 4.7 ± 2.5 years; P = 0.020). IADL score at baseline and antihypertensive/cardiac therapy, antidiabetics, and antipsychotics were independent predictors of survival after AD diagnosis in a general linear model, after controlling for sex, age, and cognitive ability. Basic ADL, number of medications, and specific concomitant medications (lipid-lowering agents, NSAIDs/acetylsalicylic acid, antidepressants, and anxiolytics/sedatives/hypnotics) at baseline were not significant predictors. Conclusions: IADL, but not basic ADL, was an important predictor that should be considered by clinicians and community-based services when estimating AD prognosis. Antidiabetic therapy was a strong risk factor for reduction in life expectancy

Various outcomes of cholinesterase inhibitor treatment influence survival of patients with Alzheimer’s disease.

Objectives: Various outcomes of cholinesterase inhibitor (ChEI) therapy have been observed in Alzheimer’s disease (AD). It is not clear whether the duration of treatment, type of ChEI, or dose affect mortality. We aimed to investigate the association between ChEI therapy and patient survival. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicentre study to evaluate long-term treatment with ChEIs in clinical practice. This study included 1021 outpatients with a clinical diagnosis of mild-to-moderate AD (Mini-Mental State Examination score, 10–26) at the start of ChEI treatment (shortly after diagnosis). The date of death of participants was recorded. Results: After up to 16 years of follow-up, 841 (82%) of the patients in the SATS had died. The mean ± standard deviation time from diagnosis of AD to death was 6.0 ± 2.9 years, and differed between individuals with varying durations of ChEI treatment in the study, from 7.2 ± 2.5 years (3-year completers) to 4.9 ± 2.9 years (<1 year) (P<0.001). Patients who received a higher mean dose of ChEIs during the study had a longer lifespan than those who received a lower dose (6.4 ± 2.9 vs 5.5 ± 2.8 years; P<0.001). The median cutoff values were donepezil 6.9 mg, rivastigmine 6.0 mg, and galantamine 15.0 mg. No difference in mortality between the types of ChEIs was found after adjusting for sex, age, and disease severity. Conclusions: Longer survival can be expected for AD patients who receive and tolerate higher ChEI doses and a longer duration of treatment