| 21. |
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| 22. |
- Lawlor, B., et al.
(författare)
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NILVAD protocol: A European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease
- 2014
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Ingår i: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks. Methods and analysis: Adult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease and Related Disorders Association (NINCDSADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimer's disease Assessment Scale (ADASCog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDRsb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDRsb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis. Ethics and dissemination: The study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peerreviewed journal. Trial registration number EUDRACT Reference Number: 201200276427.
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| 23. |
- Lawlor, B., et al.
(författare)
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Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial
- 2018
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- Background This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated antiinflammatory and anti-tau activity in preclinical studies, properties that could have diseasemodifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease. NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged > 50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of >= 12 and < 27. Participants were randomly assigned to 8 mg sustained-release nilvadipine or matched placebo. The a priori defined primary outcome was progression on the Alzheimer's Disease Assessment Scale Cognitive Subscale-12 (ADAS-Cog 12) in the modified intention-to-treat (mITT) population (n = 498), with the Clinical Dementia Rating Scale sum of boxes (CDR-sb) as a gated co-primary outcome, eligible to be promoted to primary end point conditional on a significant effect on the ADAS-Cog 12. The analysis set had a mean age of 73 years and was 62% female. Baseline demographic and Alzheimer disease +/- specific characteristics were similar between treatment groups, with reported mean of 1.7 years since diagnosis and mean SMMSE of 20.4. The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADASCog 12 on placebo was 0.79 (95% CI, -0.07 +/- 1.64) at 13 weeks, 6.41 (5.33 +/- 7.49) at 52 weeks, and 9.63 (8.33 +/- 10.93) at 78 weeks and on nilvadipine was 0.88 (0.02 +/- 1.74) at 13 weeks, 5.75 (4.66 +/- 6.85) at 52 weeks, and 9.41 (8.09 +/- 10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid. The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease.
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| 24. |
- Lesén, Eva, 1982, et al.
(författare)
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Psychotropic drug use in relation to mental disorders and institutionalization among 95-year-olds: a population-based study.
- 2011
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Ingår i: International psychogeriatrics. - 1741-203X. ; 23:8, s. 1270-1277
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of psychotropic drug use is high among the elderly, but research on how psychotropic drugs are used among individuals aged 90 years and older is limited. An increased knowledge on this topic may contribute to improved prescribing patterns in this vulnerable population. The aim of this study was to assess the use of psychotropic drugs in relation to mental disorders and institutionalization among 95-year-olds and to identify use of potentially inappropriate psychotropic drugs. Methods: All 95-year-olds born in 1901–1903 living in nursing homes or community settings in Gothenburg, Sweden were invited to participate. The response rate was 65% and 338 95-year-olds were examined (263 women, 75 men). Psychotropic drug use in relation to mental disorders and institutionalization was assessed. Information on drug use was collected primarily from multi-dose drug dispensing lists. Participants were examined by trained psychiatrists using the Comprehensive Psychopathological Rating Scale and a battery of cognitive tests. Dementia, depression, anxiety and psychotic disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R). Results: Sixty percent of the 95-year-old participants used psychotropic drugs; hypnotics were most common (44%). Potentially inappropriate psychotropics were observed in one third (33%). Antidepressants were used by 7% of the participants without dementia who fulfilled criteria for a depressive disorder, while 56% used hypnotics and 30% used anxiolytics. Conclusions: The high prevalence of psychotropic drug use and the nonspecific nature of these treatments among 95-year-olds indicate a need for improvement in prescribing patterns.
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| 25. |
- Low, W C, et al.
(författare)
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Hereditary multi-infarct dementia of the Swedish type is a novel disorder different from NOTCH3 causing CADASIL
- 2007
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 130:Part 2, s. 357-367
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Tidskriftsartikel (refereegranskat)abstract
- Several hereditary small vessel diseases (SVDs) of the brain have been reported in recent years. In 1977, Sourander and Wålinder described hereditary multi-infarct dementia (MID) in a Swedish family. In the same year, Stevens and colleagues reported chronic familial vascular encephalopathy in an English family bearing a similar phenotype. These disorders have invariably been suggested to be cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) but their genetic identities remain unknown. We used molecular, radiological and neuropathological methods to characterize these disorders. Direct DNA sequencing unexpectedly confirmed that affected members of the English family carried the R141C mutation in the NOTCH3 gene diagnostic of CADASIL. However, we did not detect any pathogenic mutations in the entire 8091 bp reading frame of NOTCH3 or find clear evidence for NOTCH3 gene linkage in the Swedish DNA. This was consistent with the lack of hyperintense signals in the anterior temporal pole and external capsule in Swedish subjects upon magnetic resonance imaging. We further found no evidence for granular osmiophilic material in skin biopsy or post-mortem brain samples of affected members in the Swedish family. In addition, there was distinct lack of NOTCH3 N-terminal fragments in the cerebral microvasculature of the Swedish hereditary MID subjects compared to the intense accumulation in the English family afflicted with CADASIL. Several differences in arteriosclerotic changes in both the grey and white matter were also noted between the disorders. The sclerotic index values, density of collagen IV immunoreactivity in the microvasculature and number of perivascular macrophages were greater in the English CADASIL samples compared to those from the Swedish brains. Multiple approaches suggest that the Swedish family with hereditary MID suspected to be CADASIL has a different novel disorder with dissimilar pathological features and belongs to the growing number of genetically uncharacterized familial SVDs.
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| 26. |
- Mellqvist Fässberg, Madeleine, et al.
(författare)
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Suicidal feelings in the twilight of life: a cross-sectional population-based study of 97-year-olds
- 2013
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the occurrence of past month suicidal feelings in extreme old age. Further, to Design: Cross-sectional population-based study. Setting: Gothenburg, Sweden. Participants: 269 adults (197 women, 72 men) without dementia born in 1901-1909 who participated Main outcome measures: Death thoughts and suicidal feelings. The latter were rated in accordance Results: One quarter of the sample (26.7%) reported that they thought about their own death at least Conclusions: Suicidal feelings may occur outside the context of depression and disability in this age
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| 27. |
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| 28. |
- Olesen, Pernille J, et al.
(författare)
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A population-based study on the influence of brain atrophy on 20-year survival after age 85.
- 2011
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Ingår i: Neurology. - 0028-3878. ; 76:10, s. 879-86
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Tidskriftsartikel (refereegranskat)abstract
- Individuals aged 80 years and older is the fastest growing segment of the population worldwide. To understand the biology behind increasing longevity, it is important to examine factors related to survival in this age group. The relationship between brain atrophy and survival after age 85 remains unclear.
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| 29. |
- Ribbe, Mats, 1985, et al.
(författare)
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Amyloid β42 and Total Tau Levels in Cerebrospinal Fluid Associate with Survival in an 85-Year-Old Population-Based Cohort Followed until Death
- 2019
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 47:1-2, s. 114-123
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dementia of Alzheimer's type (AD) is related to decreased survival. It is not clear whether also biological markers of AD are related to mortality. Low levels of amyloid beta-42 (Aβ42) and high levels of total tau (T-tau) protein in cerebrospinal fluid (CSF) are established biomarkers for AD. >bold<>italic/italic<>/bold< Our aim was to investigate whether levels of Aβ42 and T-tau are associated with survival among octogenarians independently of dementia status. >bold<>italic/italic<>/bold< Sixty-five 85-year-olds underwent lumbar puncture and were followed with repeated neuropsychiatric examinations until death.>bold<>italic< Results:>/italic<>/bold< Lower CSF Aβ42 (>italic/italic< = 0.010) and higher CSF T-tau (>italic/italic< = 0.005) at the age of 85 were associated with lower survival independently of dementia status at baseline and follow-up. Low CSF Aβ42 and high CSF T-tau were also related to baseline dementia at the age of 85 years, and lower CSF Aβ42 with increased dementia incidence during the first 3 years of follow-up. >bold<>italic/italic<>/bold< Biological markers of AD are associated with mortality in octogenarians. The reason for this needs further study. Our findings highlight the importance to consider the competing risk of death when evaluating biological markers of AD in the very old. © 2019 S. Karger AG, Basel. All rights reserved.
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| 30. |
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