| 131. |
- Wattmo, Carina, et al.
(författare)
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The course and end-points of Alzheimer’s disease according to sociodemographics, apolipoprotein E genotype and cognitive ability.
- 2017
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: The prognosis of Alzheimer’s disease (AD) might be influenced by many sociodemographic and clinical factors. Previous studies have investigated the main effects of critical predictors but few have analyzed potential interactions. We have studied the long-term cognitive outcome, nursing home placement (NHP) and mortality by interactions between factors in cholinesterase inhibitor (ChEI)-treated AD patients. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicenter study for longitudinal evaluation of ChEI treatment in clinical practice. This presentation includes 224 deceased SATS participants diagnosed with mild-to-moderate AD (Mini-Mental State Examination score (MMSE), 10–26 at the start of ChEI therapy, i.e., time of diagnosis) who were admitted to nursing homes (NHs) during the study. Cognitive abilities were evaluated at baseline and semiannually over 3 years. Dates of NHP and death were recorded. Results: Patients were divided into two groups by age at AD diagnosis, cut-off median 78 years. Younger females exhibited lower cognitive ability at NHP (mean MMSE score (95% confidence interval), 16.3 (14.9–17.7) points vs. 18.7 (17.6–19.7) points, p=0.018), and a longer time to NHP (22.1 (19.9–24.2) months vs. 15.6 (13.6–17.7) months, p<0.001), than older females. Females ≤77 years old had longer survival times in NHs, (5.4 (4.7–6.0) years), compared with the other groups: ≥78-year-old females, (4.1 (3.4–4.7) years); ≤77-year-old males, (2.8 (1.7–3.8) years); and ≥78-year-old males, (2.8 (2.0–3.5 years), p<0.001). Younger apolipoprotein E (APOE) e4-carriers demonstrated lower cognitive ability at NHP, (16.3 (14.9–17.7) points vs. 19.0 (17.9–20.1) points, p=0.021), longer time to NHP, (22.8 (20.8–24.8) months vs. 17.7 (15.4–19.9) months, p=0.006), longer survival time in NHs, (5.0 (4.4–5.7) years vs. 3.8 (3.2–4.5) years, p=0.030), and longer life-span from AD diagnosis, (6.9 (6.3–7.6) years vs. 5.3 (4.6–6.0) years, p=0.002), than older e4-carriers. Conclusions: In the ≤77-year-old group, a longer survival time in NHs (~5 years) and thus higher cost of care might be expected in females, mild AD or APOE e4-carriers. Younger patients with moderate AD showed remarkably low cognitive ability at NHP (mean MMSE score 12); these individuals might need increased support.
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| 132. |
- Wattmo, Carina, et al.
(författare)
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The effect of functional capacity and concomitant medications on life expectancy in Alzheimer’s disease.
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 133. |
- Wattmo, Carina, et al.
(författare)
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The interaction effect of sex and apolipoprotein E genotype in Alzheimer’s disease—rates of progression and prognosis.
- 2020
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Konferensbidrag (refereegranskat)abstract
- 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.
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| 134. |
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| 135. |
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| 136. |
- Wattmo, Carina, et al.
(författare)
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Various outcomes of cholinesterase inhibitor treatment influence survival of patients with Alzheimer’s disease.
- 2015
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 137. |
- Wennström, Malin, et al.
(författare)
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Altered CSF Orexin and α-Synuclein Levels in Dementia Patients.
- 2012
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877. ; 29:1, s. 125-132
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegenerative dementia, most frequently represented by Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), is often accompanied by altered sleeping patterns and excessive daytime sleepiness. Studies showing an association between the neuropeptide orexin and AD/DLB-related processes such as amyloid-β (Aβ)1-42 plaque formation, α-synuclein accumulation, and inflammation indicate that orexin might play a pathogenic role similar to the situation in narcolepsy. Our study of patients with AD (n = 26), DLB (n = 18), and non-demented controls (n = 24) shows a decrease in cerebrospinal fluid (CSF) orexin concentrations in DLB versus AD patients and controls. The observed differences in orexin levels were found to be specific to female DLB patients. We also show that the female DLB patients exclusively displayed lower levels of α-synuclein compared to AD patients and controls. Orexin was linked to α-synuclein and total-tau in female non-demented controls whereas associations between orexin and Aβ1-42 concentrations were absent in all groups regardless of gender. Thus, the proposed links between orexin, Aβ, and α-synuclein pathology could not be monitored in CSF protein concentrations. Interestingly, α-synuclein was strongly correlated to the CSF levels of total-tau in all groups, suggesting α-synuclein to be an unspecific marker of neurodegeneration. We conclude that lower levels of CSF orexin are specific to DLB versus AD and appear unrelated to Aβ1-42 and α-synuclein levels in AD and DLB. Alterations in CSF orexin and α-synuclein levels may be related to gender which warrants further investigation.
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| 138. |
- Wennström, Malin, et al.
(författare)
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Cerebrospinal fluid levels of IL-6 are decreased and correlate with cognitive status in DLB patients
- 2015
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central (BMC). - 1758-9193. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Inflammatory processes have previously been shown to influence cognition and progression of dementia. An involvement of interleukin (IL)-6 has in particular been suggested as altered levels of IL-6 in cerebrospinal fluid (CSF) have been found in patients with Alzheimer's disease (AD). Also, an association between cognitive decline and levels of IL-6 in CSF have been reported. The aim of the present study was to investigate whether patients clinically diagnosed with dementia with Lewy bodies (DLB) display altered CSF IL-6 levels in comparison with patients with AD and control subjects without dementia and whether the IL-6 levels are correlated with cognitive status and biomarkers for AD and synucleinopathy.METHODS: To analyse CSF of patients with AD (n = 45), patients with DLB (n = 29) and control subjects without dementia (n = 36), we used immunoassays to measure levels of IL-6 (multiplex electrochemiluminescence); AD markers phosphorylated tau, total tau and amyloid-β1-42 (enzyme-linked immunosorbent assay [ELISA]); and α-synuclein (ELISA). Cognitive status was evaluated using the Mini Mental State Examination (MMSE).RESULTS: Our analysis showed significantly lower levels of IL-6 in CSF from patients with DLB than in CSF from patients with AD and control subjects without dementia. The IL-6 levels were also negatively correlated with MMSE and positively correlated with α-synuclein CSF levels.CONCLUSIONS: Our findings support previous studies by demonstrating a link between inflammatory processes and dementia progression and further strengthen the hypothesis that IL-6 is involved in dementia pathology and cognitive decline.
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| 139. |
- Wennström, Malin, et al.
(författare)
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Kynurenic Acid levels in cerebrospinal fluid from patients with Alzheimer's disease or dementia with lewy bodies.
- 2014
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Ingår i: International journal of tryptophan research : IJTR. - 1178-6469. ; 7, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Kynurenic acid (KYNA) is implicated in cognitive functions. Altered concentrations of the compound are found in serum and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD). Further studies to determine whether KYNA serves as a biomarker for cognitive decline and dementia progression are required. In this study, we measured CSF KYNA levels in AD patients (n = 19), patients with dementia with Lewy bodies (DLB) (n = 18), and healthy age-matched controls (Ctrls)) (n = 20) to further explore possible correlations between KYNA levels, cognitive decline, and well-established AD and inflammatory markers. Neither DLB patients nor AD patients showed significantly altered CSF KYNA levels compared to Ctrls. However, female AD patients displayed significantly higher KYNA levels compared to male AD patients, a gender difference not seen in the Ctrl or DLB group. Levels of KYNA significantly correlated with the AD-biomarker P-tau and the inflammation marker soluble intercellular adhesion molecule-1 (sICAM-1) in the AD patient group. No associations between KYNA and cognitive functions were found. Our study shows that, although KYNA was not associated with cognitive decline in AD or DLB patients, it may be implicated in AD-related hyperphosphorylation of tau and inflammation. Further studies on larger patient cohorts are required to understand the potential role of KYNA in AD and DLB.
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| 140. |
- Wesnes, Keith A., et al.
(författare)
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Memantine improves attention and episodic memory in Parkinson's disease dementia and dementia with Lewy bodies
- 2015
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 30:1, s. 46-54
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveIn both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), attentional dysfunction is a core clinical feature together with disrupted episodic memory. This study evaluated the cognitive effects of memantine in DLB and PDD using automated tests of attention and episodic memory. MethodsA randomised double-blind, placebo-controlled, 24-week three centre trial of memantine (20mg/day) was conducted in which tests of attention (simple and choice reaction time) and word recognition (immediate and delayed) from the CDR System were administered prior to dosing and again at 12 and 24weeks. Although other results from this study have been published, the data from the CDR System tests were not included and are presented here for the first time. ResultsData were available for 51 patients (21 DLB and 30 PDD). In both populations, memantine produced statistically significant medium to large effect sized improvements to choice reaction time, immediate and delayed word recognition. ConclusionsThese are the first substantial improvements on cognitive tests of attention and episodic recognition memory identified with memantine in either DLB or PDD. Copyright (c) 2014 John Wiley & Sons, Ltd.
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