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Clinical factors associated with progression to dementia in people with late-life depression: a cohort study of patients in secondary care.

ABSTRACT: OBJECTIVES:Depression can be a prodromal feature or a risk factor for dementia. We aimed to investigate which clinical factors in patients with late-life depression are associated with a higher risk of developing dementia and a more rapid conversion. DESIGN:Retrospective cohort study. SETTING:South London and Maudsley NHS Foundation Trust (SLaM) secondary mental healthcare services. PARTICIPANTS:The SLaM Clinical Record Interactive Search was used to retrieve anonymised data on 3659 patients aged 65 years or older who had received a diagnosis of depression in mental health services and had been followed up for at least 3 months. OUTCOME MEASURES:Predictors of development of incident dementia were investigated, including demographic factors, health status rated on the Health of the National Outcome scale for older people (HoNOS65+), depression recurrence and treatments including psychotropic drugs and cognitive behavioural therapy (CBT). RESULTS:In total, 806 (22.0%) patients developed dementia over a mean follow-up time of 2.7 years. Significant predictors of receiving a dementia diagnosis in fully adjusted models and after accounting for multiple comparisons were older age (adjusted HR=1.04, 95%?CI 1.03 to 1.06 per year difference from sample mean) and the HoNOS65+ subscale measuring cognitive problems (HR=4.72, 95%?CI 3.67 to 6.06 for scores in the problematic range). Recurrent depressive disorder or past depression (HR=0.65, 95%?CI 0.55 to 0.77) and the receipt of CBT (HR=0.73 95%?CI 0.61 to 0.87) were associated with a lower dementia risk. Over time, hazards related to age increased and hazards related to cognitive problems decreased. CONCLUSIONS:In older adults with depression, a higher risk of being subsequently diagnosed with dementia was predicted by higher age, new onset depression, severity of cognitive symptoms and not receiving CBT. Further exploration is needed to determine whether the latter risk factors are responsive to interventions.

SUBMITTER: Peakman G

PROVIDER: S-EPMC7252968 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Clinical factors associated with progression to dementia in people with late-life depression: a cohort study of patients in secondary care.

Peakman Georgia G Karunatilake Nishshanka N Seynaeve Mathieu M Perera Gayan G Aarsland Dag D Stewart Robert R Mueller Christoph C

BMJ open 20200524 5

<h4>Objectives</h4>Depression can be a prodromal feature or a risk factor for dementia. We aimed to investigate which clinical factors in patients with late-life depression are associated with a higher risk of developing dementia and a more rapid conversion.<h4>Design</h4>Retrospective cohort study.<h4>Setting</h4>South London and Maudsley NHS Foundation Trust (SLaM) secondary mental healthcare services.<h4>Participants</h4>The SLaM Clinical Record Interactive Search was used to retrieve anonymi ...[more]

PMID: 32448792

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Project description:Late-life depression is associated with significant cognitive impairment. Meta-analyses showed that depression is associated with an increased risk for Alzheimer's disease (AD) and it might be an etiological factor for AD. Since late-life depression is often connected with cognitive impairment and dementia is usually associated with depressive symptoms, a simple diagnostic approach to distinguish between the disorders is challenging. Several overlapping pathophysiological substrates might explain the comorbidity of both syndromes. Firstly, a stress syndrome, i.e., elevated cortisol levels, has been observed in up to 70% of depressed patients and also in AD pathology. Stress conditions can cause hippocampal neuronal damage as well as cognitive impairment. Secondly, the development of a depression and dementia after the onset of vascular diseases, the profile of cerebrovascular risk factors in both disorders and the impairments depending on the location of cerebrovascular lesions, speak in favor of a vascular hypothesis as a common factor for both disorders. Thirdly, neuroinflammatory processes play a key role in the etiology of depression as well as in dementia. Increased activation of microglia, changes in Transforming-Growth-Factor beta1 (TGF-beta1) signaling, production of pro-inflammatory cytokines as well as reduction of anti-inflammatory molecules are examples of common pathways impaired in dementia and depression. Fourthly, the neurotrophin BDNF is highly expressed in the central nervous system, especially in the hippocampus, where it plays a key role in the proliferation, differentiation and the maintenance of neuronal integrity throughout lifespan. It has been associated not only with antidepressant properties but also a reduction of cognitive impairment and therefore could be involved also in AD. Another etiologic factor is amyloid accumulation, as plasma amyloid beta-42 independently predicts both late-onset depression and AD. Higher plasma amyloid beta-42 predicts the development of late onset depression and conversion to possible AD. However, clinical trials with antibodies against beta amyloid recently failed, i.e., Solanezumab, Aducanumab, and Crenezumab. An overproduction of amyloid-beta might simply reflect a form of synaptic plasticity to compensate for neuronal dysfunction in different kind of neurological and psychiatric diseases of multiple etiologies. The tau hypothesis, sex/gender specific differences, epigenetics and the gut microbiota-brain axis imply other potential common pathways connecting late-life depression and dementia. In conclusion, different potential pathophysiological links between dementia and depression highlight several specific synergistic and multifaceted treatment possibilities, depending on the individual risk profile of the patient.

Project description:BackgroundAs a major public health issue in China and worldwide, late-life depression is associated with physical limitations, greater functional impairment, increased utilization and cost of health care, and suicide. Like other chronic diseases in elders such as hypertension and diabetes, depression is a chronic disease that the new National Health Policy of China indicates should be managed in primary care settings. Collaborative care, linking primary and mental health specialty care, has been shown to be effective for the treatment of late-life depression in primary care settings in Western countries. The primary aim of this project is to implement a depression care management (DCM) intervention, and examine its effectiveness on the depressive symptoms of older patients in Chinese primary care settings.Methods/designThe trial is a multi-site, primary clinic based randomized controlled trial design in Hangzhou, China. Sixteen primary care clinics will be enrolled in and randomly assigned to deliver either DCM or care as usual (CAU) (8 clinics each) to 320 patients (aged ≥ 60 years) with major depression (20/clinic; n = 160 in each treatment condition). In the DCM arm, primary care physicians (PCPs) will prescribe 16 weeks of antidepressant medication according to the treatment guideline protocol. Care managers monitor the progress of treatment and side effects, educate patients/family, and facilitate communication between providers; psychiatrists will provide weekly group psychiatric consultation and CM supervision. Patients in both DCM and CAU arms will be assessed by clinical research coordinators at baseline, 4, 8, 12, 18, and 24 months. Depressive symptoms, functional status, treatment stigma and clients' satisfaction will be used to assess patients' outcomes; and clinic practices, attitudes/knowledge, and satisfaction will be providers' outcomes.DiscussionThis will be the first trial of the effectiveness of a collaborative care intervention aiming to the management of late-life depression in China primary care. If effective, its finding will have relevance to policy makers who wish to scale up DCM treatments for late-life depression in national wide primary care across China.Study registrationThe DCM project is registered through the National Institutes of Health sponsored by clinical trials registry and has been assigned the identifier: NCT01287494.

Project description:Objective: Late-life depression (LLD) is associated with development of different types of dementia. Identification of LLD patients, who will develop cognitive decline, i.e., the early stage of dementia would help to implement interventions earlier. The purpose of this study was to assess whether structural brain magnetic resonance imaging (MRI) in LLD patients can predict mild cognitive impairment (MCI) or dementia 1 year prior to the diagnosis. Methods: LLD patients underwent brain MRI at baseline and repeated clinical assessment after 1-year. Structural brain measurements were obtained using Freesurfer software (v. 5.1) from the T1W brain MRI images. MRI-based Random Forest classifier was used to discriminate between LLD who developed MCI or dementia after 1-year follow-up and cognitively stable LLD. Additionally, a previously established Random Forest model trained on 185 patients with Alzheimer's disease (AD) vs. 225 cognitively normal elderly from the Alzheimer's disease Neuroimaging Initiative was tested on the LLD data set (ADNI model). Results: MCI and dementia diagnoses were predicted in LLD patients with 76%/68%/84% accuracy/sensitivity/specificity. Adding the baseline Mini-Mental State Examination (MMSE) scores to the models improved accuracy/sensitivity/specificity to 81%/75%/86%. The best model predicted MCI status alone using MRI and baseline MMSE scores with accuracy/sensitivity/specificity of 89%/85%/90%. The most important region for all the models was right ventral diencephalon, including hypothalamus. Its volume correlated negatively with the number of depressive episodes. ADNI model trained on AD vs. Controls using SV could predict MCI-DEM patients with 67% accuracy. Conclusion: LDD patients developing MCI and dementia can be discriminated from LLD patients remaining cognitively stable with good accuracy based on baseline structural MRI alone. Baseline MMSE score improves prediction accuracy. Ventral diencephalon, including the hypothalamus might play an important role in preservation of cognitive functions in LLD.

Dataset Information

Clinical factors associated with progression to dementia in people with late-life depression: a cohort study of patients in secondary care.

Publications

Clinical factors associated with progression to dementia in people with late-life depression: a cohort study of patients in secondary care.

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