Obstructive sleep apnea (OSA) is highly prevalent but very frequently undiagnosed. OSA is an independent risk factor for depression and cognitive impairment/dementia. Herein the authors review studies in the literature pertinent to the effects of OSA on the cerebral microvascular and neurovascular systems and present a model to describe the key pathophysiologic mechanisms that may underlie the associations, including hypoperfusion, endothelial dysfunction, and neuroinflammation. Intermittent hypoxia plays a critical role in initiating and amplifying these pathologic processes. Hypoperfusion and impaired cerebral vasomotor reactivity lead to the development or progression of cerebral small vessel disease (C-SVD). Hypoxemia exacerbates these processes, resulting in white matter lesions, white matter integrity abnormalities, and gray matter loss. Blood–brain barrier (BBB) hyperpermeability and neuroinflammation lead to altered synaptic plasticity, neuronal damage, and worsening C-SVD. Thus, OSA may initiate or amplify the pathologic processes of C-SVD and BBB dysfunction, resulting in the development or exacerbation of depressive symptoms and cognitive deficits. Given the evidence that adequate treatment of OSA with continuous positive airway pressure improves depression and neurocognitive functions, it is important to identify OSA when assessing patients with depression or cognitive impairment. Whether treatment of OSA changes the deteriorating trajectory of elderly patients with already-diagnosed vascular depression and cognitive impairment/dementia remains to be determined in randomized controlled trials.
SUMMARY Electroconvulsive therapy (ECT) is utilized worldwide for various severe and treatment-resistant psychiatric disorders. Research studies have shown that ECT is the most effective and rapid treatment available for elderly patients with depression, bipolar disorder and psychosis. For patients who suffer from intractable catatonia and neuroleptic malignant syndrome, ECT can be life saving. For elderly patients who cannot tolerate or respond poorly to medications and who are at a high risk for drug-induced toxicity or toxic drug interactions, ECT is the safest treatment option. Organic causes are frequently associated with late-life onset of neuropsychiatric conditions, such as parkinsonism, dementia and stroke. ECT has proven to be efficacious even when these conditions are present. During the next decade, research studies should focus on the use of ECT as a synergistic therapy, to enhance other biological and psychological treatments, and prevent symptom relapse and recurrence.
IntroductionMild cognitive impairment (MCI) is common in older adults and represents a high-risk group for progression to Alzheimer’s disease (AD). Medication trials in MCI have generally failed, but new discoveries with brain plasticity in ageing have led to the study of cognitive training as a potential treatment to improve cognitive abilities. Computerised cognitive training (CCT) involves computerised cognitive exercises that target specific cognitive abilities and neural networks to potentially improve cognitive functioning through neuroplasticity.Methods and analysisIn a two-site study (New York State Psychiatric Institute/Columbia University Medical Center and Duke University Medical Center), we will randomise 100 patients with MCI (Wechsler Memory Scale-III Logical Memory II score 0–11; Folstein Mini Mental State Examination ≥23) to home-based CCT (suite of exercises: memory, matching, spatial recognition, processing speed) or a home-based active control condition (computerised crossword puzzle training (CPT)) with 12 weeks of intensive training followed by regular booster sessions up to 78 weeks. All patients will receive standard neuropsychological and functional assessments in clinic as well as structural/functional brain MRI scans at study entry and endpoint. We will test if CCT, versus CPT, leads to improved cognitive functioning, transfers to functional ability and tasks of everyday life and impacts hippocampal volume changes and changes in the default mode network of the brain measured by resting-state functional MRI.Ethics and disseminationThe study will be conducted following ethics approval and written informed consent will be obtained from all subjects. Study results will be disseminated via publication, clinicaltrials.gov, media and conference presentations. This will be the first controlled long-term trial to evaluate the effects of home-based CCT versus computerised CPT on cognitive abilities and functional measures and neural outcomes as determined by MRI indices in patients with MCI. Positive results from trial may support further development of home-based CCT.Trial registration numberClinicalTrials.gov identifier (NCT03205709).
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