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| 14. |
- Enache, D., et al.
(författare)
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Antidepressants and mortality risk in a dementia cohort : data from SveDem, the Swedish Dementia Registry
- 2016
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 134:5, s. 430-440
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association between mortality risk and use of antidepressants in people with dementia is unknown. Objective: To describe the use of antidepressants in people with different dementia diagnoses and to explore mortality risk associated with use of antidepressants 3 years before a dementia diagnosis. Methods: Study population included 20 050 memory clinic patients from the Swedish Dementia Registry (SveDem) diagnosed with incident dementia. Data on antidepressants dispensed at the time of dementia diagnosis and during 3-year period before dementia diagnosis were obtained from the Swedish Prescribed Drug Register. Cox regression models were used. Results: During a median follow-up of 2 years from dementia diagnosis, 25.8% of dementia patients died. A quarter (25.0%) of patients were on antidepressants at the time of dementia diagnosis, while 21.6% used antidepressants at some point during a 3-year period before a dementia diagnosis. Use of antidepressant treatment for 3 consecutive years before a dementia diagnosis was associated with a lower mortality risk for all dementia disorders and in Alzheimer's disease. Conclusion: Antidepressant treatment is common among patients with dementia. Use of antidepressants during prodromal stages may reduce mortality in dementia and specifically in Alzheimer's disease.
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| 15. |
- Enache, D, et al.
(författare)
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Antidepressants and mortality risk in a dementia cohort - data from SveDem, the Swedish Dementia Registry
- 2016
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Ingår i: EUROPEAN PSYCHIATRY. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 33, s. S85-S85
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The association between mortality risk and use of antidepressants in people with dementia is unknown.ObjectiveTo describe the use of antidepressants in people with different dementia diagnoses and to explore mortality risk associated with use of antidepressants 3 years before a dementia diagnosis.MethodsStudy population included 20,050 memory clinic patients from Swedish Dementia Registry diagnosed with incident dementia. Data on antidepressants dispensed at the time of dementia diagnosis and during three-year period before dementia diagnosis was obtained from the Swedish Prescribed Drug Register. Cox regression models were used.ResultsDuring a median follow-up of 2 years from dementia diagnosis, 25.8% of dementia patients died. A quarter (25.0%) of patients were on antidepressants at the time of dementia diagnosis while 21.6% used antidepressants at some point during a three-year period before a dementia diagnosis. Use of antidepressant treatment for 3 consecutive years before a dementia diagnosis was associated with a lower mortality risk for all dementia disorders (HR: 0.82, 95% CI: 0.72–0.94) and in Alzheimer's disease (HR: 0.61, 95% CI: 0.45–0.83). There were no significant associations between use of antidepressant treatment and mortality risk in other dementia diagnoses.ConclusionAntidepressant treatment is common among patients with dementia. Use of antidepressants during prodromal stages may reduce mortality in dementia and specifically in Alzheimer's disease.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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| 16. |
- Enache, D, et al.
(författare)
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Medial temporal lobe atrophy and depressive symptoms in elderly patients with and without Alzheimer disease
- 2015
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Ingår i: Journal of geriatric psychiatry and neurology. - : SAGE Publications. - 0891-9887 .- 1552-5708. ; 28:1, s. 40-48
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Tidskriftsartikel (refereegranskat)abstract
- To determine whether depressive symptoms are associated with medial temporal lobe atrophy in older people with and without Alzheimer disease (AD).Method:A total of 368 memory clinic patients with AD, mild cognitive impairment, and subjective cognitive impairment (SCI) were included. Depressive symptoms were defined as a score of 8 or higher on Cornell Scale for Depression in Dementia or use of antidepressant medications. Magnetic resonance imaging and computer tomography scans were rated for medial temporal lobe atrophy (MTA), using the Scheltens scale. For a subsample (n = 57 patients), hippocampal volume was manually traced.Results:Based on visual assessment, AD patients with depressive symptoms had less atrophy of the right medial temporal lobe (odds ratio [OR] for having MTA: 0.39; 95% confidence interval [CI] 0.16-0.99) and decreased scores on Scheltens scale for the left medial temporal lobe (OR: 0.43, 95% CI 0.19-0.96) in comparison to AD patients without depressive symptoms. In the subgroup where manual tracing was used to measure hippocampal volume, people with SCI experiencing depressive symptoms had smaller right (mean difference: 0.28 cm3; P = .005) and left (mean difference 0.32 cm3; P = .002) hippocampal volumes compared to people with SCI who did not have depressive symptoms.Conclusion:Hippocampal atrophy was more pronounced among patients having SCI with depressive symptoms, while the medial temporal lobe was less atrophic in patients having AD with depressive symptoms than those without depressive symptoms. These findings suggest that different mechanisms underlie depression in older people with and without AD and may explain some of the inconsistent observations in previous studies.
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| 17. |
- Eyjolfsdottir, H., et al.
(författare)
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Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients: application of a second-generation encapsulated cell biodelivery device
- 2016
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Targeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer's disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis has been tested in patients with AD using encapsulated cell biodelivery of NGF (NGF-ECB) in a first-in-human study. We report our results from a third-dose cohort of patients receiving second-generation NGF-ECB implants with improved NGF secretion. Methods: Four patients with mild to moderate AD were recruited to participate in an open-label, phase Ib dose escalation study with a 6-month duration. Each patient underwent stereotactic implant surgery with four NGF-ECB implants targeted at the cholinergic basal forebrain. The NGF secretion of the second-generation implants was improved by using the Sleeping Beauty transposon gene expression technology and an improved three-dimensional internal scaffolding, resulting in production of about 10 ng NGF/device/day. Results: All patients underwent successful implant procedures without complications, and all patients completed the study, including implant removal after 6 months. Upon removal, 13 of 16 implants released NGF, 8 implants released NGF at the same rate or higher than before the implant procedure, and 3 implants failed to release detectable amounts of NGF. Of 16 adverse events, none was NGF-, or implant-related. Changes from baseline values of cholinergic markers in cerebrospinal fluid (CSF) correlated with cortical nicotinic receptor expression and Mini Mental State Examination score. Levels of neurofilament light chain (NFL) protein increased in CSF after NGF-ECB implant, while glial fibrillary acidic protein (GFAP) remained stable. Conclusions: The data derived from this patient cohort demonstrate the safety and tolerability of sustained NGF release by a second-generation NGF-ECB implant to the basal forebrain, with uneventful surgical implant and removal of NGF-ECB implants in a new dosing cohort of four patients with AD.
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| 20. |
- Frisoni, G. B., et al.
(författare)
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Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers
- 2017
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Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 16:8, s. 661-676
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Tidskriftsartikel (refereegranskat)abstract
- The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimer's disease, adapted from the approach for cancer biomarkers. Sufficient evidence of analytical validity (phase 1 of a structured framework adapted from oncology) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete. To complete these phases, research priorities include the standardisation of the readout of these assays and thresholds for normality, the evaluation of their performance in detecting early disease, the development of diagnostic algorithms comprising combinations of biomarkers, and the development of clinical guidelines for the use of biomarkers in qualified memory clinics.
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