Damien Gallagher

Depressive symptoms and cognitive decline: A longitudinal analysis of potentially modifiable risk factors in community dwelling older adults

BACKGROUND Depressive symptoms have been associated with increased risk of cognitive decline in later life. There are no interventions proven to reduce risk of cognitive decline in older adults with depression, and it is unclear how these effects are mediated. We aim to determine what mediates the relationship between depressive symptoms and cognitive decline in later life. METHODS Seven thousand six hundred and sixty six community dwelling older adults (age ≥ 50) from the English Longitudinal study of Ageing (ELSA) underwent clinical assessment. Inflammation was assessed with C Reactive Protein and depressive symptoms were assessed with the 8-item version of the Center for Epidemiologic Studies (CESD) scale. RESULTS Five thousand, five hundred and ninety (73.5%) had a follow-up cognitive assessment after a median of 47 months. Depressive symptoms were independently associated with cognitive decline (B=0.09, p<0.001). Low physical activity, inflammation, metabolic syndrome and vascular risk factors were associated with elevated depressive symptoms. Low physical activity (z=2.16, p=0.03) and inflammation (z=2.3, p=0.02) mediated the relationship between depressive symptoms and cognitive decline while hypertension, diabetes and smoking also contributed. LIMITATIONS This is an observational study with a limited duration of follow up. Not all variables related to cognitive decline were accounted for in this analysis. CONCLUSIONS The relationship between depressive symptoms and cognitive decline in later life appears to be mediated by low physical activity, increased inflammation and vascular risk factors that may be amenable to modification.

Antiepileptic Drugs for the Treatment of Agitation and Aggression in Dementia: Do They Have a Place in Therapy?

Antiepileptic drugs (AEDs) are a class of medications that have received considerable attention as possible treatments for agitation and aggression in patients with dementia. This attention has been driven in equal measure by promising findings from limited trial and observational data and the desire to find treatments with improved tolerability. Their use, to date, has been largely confined to circumstances where first-line treatments have proven inadequate or are poorly tolerated. In recent years there has been some growth in the evidence base, and we can now make more informed recommendations regarding a number of older AEDs. Carbamazepine continues to have the best evidence to support its use, although the evidence base remains relatively small and concerns regarding tolerability limit its use. There is now more consistent evidence that valproate preparations should not be used for agitation and aggression in dementia. Despite a lack of high-quality data, some results have been reported for several newer medications, including levetiracetam, oxcarbazepine, gabapentin, topiramate and lamotrigine, and a number of these warrant further investigation. Recent findings and implications for clinical practice are discussed.

Evidence for Inflammation-Associated Depression

This chapter explores the evidence supporting inflammation-associated depression. Data to date suggest a bidirectional relationship between inflammation and depression wherein one process can drive the other. A wealth of animal and clinical studies have demonstrated an association between concentrations of pro-inflammatory cytokines - specifically interleukin (IL)-1β, IL-6, and tumor necrosis factor-α - and depressive symptoms. There is also evidence that this pro-inflammatory state is accompanied by aberrant inflammation-related processes including platelet activation factor hyperactivity, oxidative and nitrosative stress, and damage to mitochondria. These complex and interrelated mechanisms can collectively contribute to negative neurobiological outcomes that may, in part, underlie the etiopathology of depression. Mounting evidence has shown a concomitant reduction in both depressive symptoms and pro-inflammatory cytokine concentrations following treatment with pharmacological anti-inflammatory interventions. Taken together, the reviewed preclinical and clinical findings may suggest the existence of a distinct inflammatory subtype of depression in which these patients exhibit unique biochemical and clinical features and may potentially experience improved clinical outcomes with inflammation-targeted pharmacotherapy.

Neuropsychiatric Symptoms in Mild Cognitive Impairment: An Update on Prevalence, Mechanisms, and Clinical Significance

Objective: Neuropsychiatric symptoms (NPS) may be the first manifestation of an underlying neurocognitive disorder. We undertook a review to provide an update on the epidemiology and etiological mechanisms of NPS that occur in mild cognitive impairment (MCI) and just before the onset of MCI. We discuss common clinical presentations and the implications for diagnosis and care. Method: The authors conducted a selective review of the literature regarding the emergence of NPS in late life, before and after the onset of MCI. We discuss recent publications that explore the epidemiology and etiological mechanisms of NPS in the earliest clinical stages of these disorders. Results: NPS have been reported in 35% to 85% of adults with MCI and also occur in advance of cognitive decline. The occurrence of NPS for the first time in later life should increase suspicion for an underlying neurocognitive disorder. The presenting symptom may provide a clue regarding the etiology of the underlying disorder, and the co-occurrence of NPS may herald a more accelerated cognitive decline. Conclusions: NPS are prevalent in the early clinical stages of neurocognitive disorders and can serve as both useful diagnostic and prognostic indicators. Recognition of NPS as early manifestations of neurocognitive disorders will become increasingly important as we move towards preventative strategies and disease-modifying treatments that may be most effective when deployed in the earliest stages of disease.

Agitation and aggression in Alzheimer's disease: an update on pharmacological and psychosocial approaches to care

Agitation and aggression are prevalent in Alzheimers disease and have significant consequences for the patient, caregiver and care system more generally. We briefly discuss the epidemiology and etiology of agitation and aggression in Alzheimers disease and provide an overview of assessment and approaches to care. We then review the evidence for and against a number of pharmacological and psychosocial approaches to care. There has been a growth in the evidence base for psychosocial interventions and nonpharmacological approaches to care should ordinarily be the first option. Antipsychotics remain the pharmacological agents with most evidence to support their use while there is more limited evidence for other agents such as carbamazepine and selective serotonin reuptake inhibitors such as citalopram.

Suicide in the oldest old: an observational study and cluster analysis.

The older population are at a high risk for suicide. This study sought to learn more about the characteristics of suicide in the oldest‐old and to use a cluster analysis to determine if oldest‐old suicide victims assort into clinically meaningful subgroups.

Cognitive Outcomes After Transcatheter Aortic Valve Implantation: A Metaanalysis

To quantitatively summarize changes in cognitive performance in individuals with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI).

Exercise for Cognitive Symptoms in Depression: A Systematic Review of Interventional Studies:

Objective: To explore the effect of exercise on cognition in depression as well as the impact of potential moderators and intervention type. Method: Controlled and uncontrolled interventional studies that described an exercise intervention and cognitive outcomes in participants with major depressive disorder (MDD) were included following a search of Pubmed, Ovid Medline, PsycInfo and Embase from inception to January 2017. Meta-analyses were conducted to calculate Hedges’ g using a random-effects model. Meta-regression explored the relationships among age, baseline cognition, frequency and duration of exercise, and cognitive outcomes. Subgroup analyses were also conducted according to type and intensity of exercise interventions. Results: Of 12 controlled studies and 3 uncontrolled studies that met inclusion criteria, 9 (642 patients) were included in the meta-analysis. No significant effect of exercise was found on global cognition (Hedges’ g = 0.08, P = 0.33, I2 = 0%) or on individual cognitive domains. Meta-regression analyses failed to find significant relationships among participant age, baseline cognition, number of exercise sessions per wk, duration of exercise per wk, total duration of exercise during the intervention, or improvement in global cognition. Interventions combining physical with cognitive activity significantly improved global cognition (P = 0.048), whereas low-intensity interventions were also positive (P = 0.048). Conclusions: No impact of physical exercise was found on cognition in MDD overall. However, we found that interventions combining physical and cognitive activities had a positive impact, and that lower-intensity interventions, where adherence was improved, also impacted positively. There remains a lack of high-quality data in this population.

Using transcranial direct current stimulation to treat symptoms in mild cognitive impairment and Alzheimer's disease

Transcranial direct current stimulation (tDCS) has recently been investigated as a potential nonpharmacological treatment for individuals with mild cognitive impairment (MCI) and Alzheimers disease (AD). A comprehensive literature search was performed on tDCS studies published until March 2017 using MEDLINE, Embase and PsychINFO databases. 12 articles with a total of 202 MCI or AD participants were included. Although ten of the 12 studies demonstrated positive findings with tDCS, two studies reported no effect on cognition. There was a wide range of methodological approaches used and in the cognitive functions measured. The variability in treatment response may be related to the heterogeneity in stimulation parameters including the site of stimulation, and cognitive assessments used. Patient-related factors including individual psychological, biological, and physiological status at the time of stimulation may also influence treatment response. We recommend that more comparative studies using similar patient factors and study parameters are needed in order to better understand the efficacy of tDCS in MCI and AD.

Depression with inflammation: longitudinal analysis of a proposed depressive subtype in community dwelling older adults.

It has been proposed that inflammation may be causally related to depression. If this is the case, it may be possible to distinguish an inflammatory depressive subtype according to illness course, pattern of co‐morbidity and symptom profile.