Importance Depression is common in individuals with mild cognitive impairment (MCI) and may confer a higher likelihood of progression to dementia. Prevalence estimates of depression in those with MCI are required to guide both clinical decisions and public health policy, but published results are variable and lack precision. Objective To provide a precise estimate of the prevalence of depression in individuals with MCI and identify reasons for heterogeneity in the reported results. Data sources A search of literature from database inception to March 2016 was performed using Medline, Embase, and PsycINFO. Hand searching of all included articles was performed, including a Google Scholar search of citations of included articles. Study selection Articles were included if they (1) were published in English, (2) reported patients with MCI as a primary study group, (3) reported depression or depressive symptoms using a validated instrument, and (4) reported the prevalence of depression in patients with MCI. Data extraction and synthesis All abstracts, full-text articles, and other sources were reviewed, with data extracted in duplicate. The overall prevalence of depression in patients with MCI was pooled using a random-effects model. Heterogeneity was explored using stratification and random-effects meta-regression. Main outcomes and measures The prevalence of depression in patients with MCI, reported as a percentage with 95% CIs. Estimates were also stratified by population source (community-based or clinic-based sample), method of depression diagnosis (clinician-administered, informant-based, or self-report), and method of MCI diagnosis (cognitive vs global measure and amnestic vs nonamnestic). Results Of 5687 unique abstracts, 255 were selected for full-text review, and 57 studies, representing 20 892 patients, met all inclusion criteria. The overall pooled prevalence of depression in patients with MCI was 32% (95% CI, 27-37), with significant heterogeneity between estimates (I2 = 90.7%). When stratified by source, the prevalence of depression in patients with MCI in community-based samples was 25% (95% CI, 19-30) and was 40% (95% CI, 32-48) in clinic-based samples, which was significantly different (P Conclusions and relevance The prevalence of depression in patients with MCI is high. A contributor to heterogeneity in the reported literature is the source of the sample, with greater depression burden prevalent in clinic-based samples.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/2587078/yoi160084.pdf

Prevalence of Depression in Patients With Mild Cognitive Impairment: A Systematic Review and Meta-analysis.

Summary Nearly half of all adults older than 60 years of age report sleep disturbance, as characterised either by reports of insomnia complaints with daytime consequences, dissatisfaction with sleep quality or quantity, or the diagnosis of insomnia disorder. Accumulating evidence shows that sleep disturbance contributes to cognitive decline and might also increase the risk of Alzheimer's disease dementia by increasing β-amyloid burden. That sleep disturbance would be a candidate risk factor for Alzheimer's disease might seem surprising, given that disturbed sleep is usually considered a consequence of Alzheimer's disease. However, a bidirectional relationship between sleep and Alzheimer's disease is supported by advances in our understanding of sleep disturbance-induced increases in systemic inflammation, which can be viewed as an early event in the course of Alzheimer's disease. Inflammation increases β-amyloid burden and is thought to drive Alzheimer's disease pathogenesis. Improved understanding of the mechanisms linking sleep disturbance and Alzheimer's disease risk could facilitate the identification of targets for prevention, given that both sleep disturbance and inflammatory activation might be modifiable risk factors for Alzheimer's disease.

Implications of sleep disturbance and inflammation for Alzheimer's disease dementia

Vascular depression is regarded as a subtype of late-life depression characterized by a distinct clinical presentation and an association with cerebrovascular damage. Although the term is commonly used in research settings, widely accepted diagnostic criteria are lacking and vascular depression is absent from formal psychiatric manuals such as the Diagnostic and Statistical Manual of Mental Disorders, 5th edition – a fact that limits its use in clinical settings. Magnetic resonance imaging (MRI) techniques, showing a variety of cerebrovascular lesions, including extensive white matter hyperintensities, subcortical microvascular lesions, lacunes, and microinfarcts, in patients with late life depression, led to the introduction of the term “MRI-defined vascular depression”. This diagnosis, based on clinical and MRI findings, suggests that vascular lesions lead to depression by disruption of frontal–subcortical–limbic networks involved in mood regulation. However, despite multiple MRI approaches to shed light on the spatiotemporal structural changes associated with late life depression, the causal relationship between brain changes, related lesions, and late life depression remains controversial. While postmortem studies of elderly persons who died from suicide revealed lacunes, small vessel, and Alzheimer-related pathologies, recent autopsy data challenged the role of these lesions in the pathogenesis of vascular depression. Current data propose that the vascular depression connotation should be reserved for depressed older patients with vascular pathology and evident cerebral involvement. Based on current knowledge, the correlations between intra vitam neuroimaging findings and their postmortem validity as well as the role of peripheral markers of vascular disease in late life depression are discussed. The multifold pathogenesis of vascular depression as a possible subtype of late life depression needs further elucidation. There is a need for correlative clinical, intra vitam structural and functional MRI as well as postmortem MRI and neuropathological studies in order to confirm the relationship between clinical symptomatology and changes in specific brain regions related to depression. To elucidate the causal relationship between regional vascular brain changes and vascular depression, animal models could be helpful. Current treatment options include a combination of vasoactive drugs and antidepressants, but the outcomes are still unsatisfying.

/pdf/vascular-depression-consensus-report-a-critical-update-3bg7t20auh.pdf

Vascular depression consensus report - a critical update.

Cognitive comorbidities are very common in epilepsy and often seen as secondary to epilepsy or caused by epilepsy. The implicit and sometimes explicit assumption is that epilepsy (i.e. having seizures) damages the brain and thus leads to functional deterioration and behavioral alterations. This article highlights the historical background surrounding this viewpoint which is characterized by old reports on 'epileptic dementia' and the fact that most cognitive research in chronic epilepsies is done retrospectively. The central question of the present article is whether there is a bidirectional relationship between epilepsy and cognition. In this regard it is essential to disentangle what is the disease and what is the symptom. Cognitive problems often exist from the onset of epilepsy, if not before, and the impact of epilepsy on cognition cannot be discerned without also considering the underlying brain pathology and its dynamics. Unraveling the etiologies of epilepsy increasingly reveals conditions wherein epilepsy, cognitive and behavioral problems are all symptoms of a common underlying pathological condition. Functional reserve capacities determine the outcome of epilepsy and its treatment. A functional interrelationship exists between epilepsy and behavior, since epileptic activity can affect behavior and behavior can alter epileptic activity. In conclusion, an epilepsy-centric unidirectional view of the behavioral problems being caused by epilepsy is obsolete. Such a view may even prevent the search for and treatment of the underlying etiological factors. Instead a practical clinical approach is favored according to which the comorbidities of epilepsy must be diagnosed at the onset of the disease, and according to which comorbidities may require separate treatment approaches.

Epilepsy and cognition - A bidirectional relationship?

Depression is caused by a change in neural activity resulting from an increase in glutamate that drives excitatory neurons and may be responsible for the decline in the activity and number of the GABAergic inhibitory neurons. This imbalance between the excitatory and inhibitory neurons may contribute to the onset of depression. At the cellular level there is an increase in the concentration of intracellular Ca2+ within the inhibitory neurons that is driven by an increase in entry through the NMDA receptors (NMDARs) and through activation of the phosphoinositide signaling pathway that generates inositol trisphosphate (InsP3) that releases Ca2+ from the internal stores. The importance of these two pathways in driving the elevation of Ca2+ is supported by the fact that depression can be alleviated by ketamine that inhibits the NMDARs and scopolamine that inhibits the M1 receptors that drive InsP3/Ca2+ pathway. This increase in Ca2+ not only contributes to depression but it may also explain why individuals with depression have a strong likelihood of developing Alzheimer's disease. The enhanced levels of Ca2+ may stimulate the formation of Aβ to initiate the onset and progression of Alzheimer's disease. Just how vitamin D acts to reduce depression is unclear. The phenotypic stability hypothesis argues that vitamin D acts by reducing the increased neuronal levels of Ca2+ that are driving depression. This action of vitamin D depends on its function to maintain the expression of the Ca2+ pumps and buffers that reduce Ca2+ levels, which may explain how it acts to reduce the onset of depression.

https://pharmrev.aspetjournals.org/content/pharmrev/69/2/80.full.pdf

Vitamin D and Depression: Cellular and Regulatory Mechanisms

Objective
There is a long-standing debate in the literature whether depressive symptoms increase the risk of dementia in older with mild cognitive impairment (MCI). We aim to conduct a meta-analysis of studies that evaluated the risk of dementia in subjects with MCI and depressive symptoms compared with subjects with MCI and no depressive symptoms.

Methods
We calculated the relative risk of progression to dementia in subjects with MCI and depressive symptoms compared with subjects with MCI and no depressive symptoms using a generic inverse variance method with random effect models.

Results
Eighteen studies were included in the meta-analysis, with a sample size of 10,861 MCI subjects. The pooled relative risk of progressing to dementia was 1.28 CI95% [1.09–1.52] (p = 0.003) in the group of MCI subjects with depressive symptoms compared with the MCI subjects with no depressive symptoms.

Discussion
Our results provide additional evidence that depressive symptoms determine an additive risk effect to the progression to dementia in subjects with MCI. The comorbidity between depression and cognitive impairment can be an intervention target for prevention of dementia in MCI subjects. Copyright © 2015 John Wiley & Sons, Ltd.

Guilherme Mansur

Papers

Depressive symptoms increase the risk of progression to dementia in subjects with mild cognitive impairment: systematic review and meta-analysis