Sleep-wake behavior, perceived fatigability, and cognitive reserve in older adults.

Introduction: The effects of sleep-wake behavior on perceived fatigability and cognitive abilities when performing daily activities have not been investigated across levels of cognitive reserve (CR).

Methods: CR Index Questionnaire (CRIq) data were collected and subjected to moderated mediation analysis.

Results: In amnestic mild cognitive impairment (aMCI; n = 41), CR moderated sleep-related impairments (SRIs), and fatigability at low CR (CRIq < 105.

Cortical thickness predicts remission of depression with antidepressants in patients with late-life depression and cognitive impairment.

Background: Depression (DEP) and cognitive impairment (CI) share etiological risk factors, anatomical underpinnings, and interact to produce deleterious treatment outcomes. Both DEP and CI exhibit altered patterns of cortical thickness which may impact the course of antidepressant treatment, though inconsistencies in directionality and affected brain regions have been reported. In this study, we examined the relationship between cortical thickness and treatment outcome in older adults with comorbid DEP-CI.

Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial.

Background: A case series suggested efficacy for lithium to treat agitation in dementia, but no placebo-controlled trials have been conducted.

Objectives: To evaluate low-dose lithium treatment of agitation in Alzheimer's disease (AD).

Method: In a four-site trial, patients with AD and agitation/aggression score ≥4 on the Neuropsychiatric Inventory (NPI) were randomized, double-blind, to lithium carbonate 150-600 mg daily or placebo for 12 weeks.

Antiviral therapy: Valacyclovir Treatment of Alzheimer's Disease (VALAD) Trial: protocol for a randomised, double-blind,placebo-controlled, treatment trial.

Introduction: After infection, herpes simplex virus-1 (HSV1) becomes latent in the trigeminal ganglion and can enter the brain via retrograde axonal transport. Recurrent reactivation of HSV1 may lead to neurodegeneration and Alzheimer's disease (AD) pathology. HSV1 (oral herpes) and HSV2 (genital herpes) can trigger amyloid beta-protein (Aβ) aggregation and HSV1 DNA is common in amyloid plaques.

Donepezil Treatment in Patients With Depression and Cognitive Impairment on Stable Antidepressant Treatment: A Randomized Controlled Trial.

Objective: Depression and cognitive impairment are often comorbid in older adults, but optimal treatment strategies remain unclear. In a two-site study, the efficacy and safety of add-on donepezil versus placebo were compared in depressed patients with cognitive impairment receiving stable antidepressant treatment.

Methods: A randomized, double-blind, placebo-controlled trial was conducted in older adults with depression and cognitive impairment (https://clinicaltrials.

Lithium Treatment for Agitation in Alzheimer's disease (Lit-AD): Clinical rationale and study design.

Unlabelled: Symptoms of agitation, aggression, and psychosis frequently occur in patients with Alzheimer's disease (AD). These symptoms are distressing to patients and caregivers, often lead to institutionalization, are associated with increased mortality, and are very difficult to treat. Lithium is an established treatment for bipolar and other psychotic disorders in which agitation can occur.

Odor Identification Ability Predicts PET Amyloid Status and Memory Decline in Older Adults.

Background: Odor identification deficits occur in Alzheimer's disease (AD), as measured by the 40-item University of Pennsylvania Smell Identification Test (UPSIT).

Objective: To determine if UPSIT scores predict amyloid-β (Aβ) status, determined by 11C-Pittsburgh Compound B PET. We also compared UPSIT scores to Aβ status in predicting future memory decline.

Change in Odor Identification Impairment is Associated with Improvement with Cholinesterase Inhibitor Treatment in Mild Cognitive Impairment.

Background: Anticholinergic challenge can induce odor identification impairment that indicates Alzheimer's disease pathology.

Objective: To determine if decline in odor identification ability with anticholinergic challenge can predict improvement with donepezil, a cholinesterase inhibitor (ChEI), in patients with mild cognitive impairment (MCI).

Methods: At baseline, the University of Pennsylvania Smell identification Test (UPSIT) was administered before and after an anticholinergic atropine nasal spray challenge.

Utility of Molecular and Structural Brain Imaging to Predict Progression from Mild Cognitive Impairment to Dementia.

This project compares three neuroimaging biomarkers to predict progression to dementia in subjects with mild cognitive impairment (MCI). Eighty-eight subjects with MCI and 40 healthy controls (HCs) were recruited. Subjects had a 3T magnetic resonance imaging (MRI) scan, and two positron emission tomography (PET) scans, one with Pittsburgh compound B ([11C]PIB) and one with fluorodeoxyglucose ([18F]FDG).

Association of Obstructive Sleep Apnea with Episodic Memory and Cerebral Microvascular Pathology: A Preliminary Study.

Objectives: To evaluate the impact of obstructive sleep apnea (OSA) on neurocognitive function and brain morphology in older adults with depression and cognitive impairment.

Methods: We prospectively screened OSA with the STOP-Bang questionnaire in the last 25 patients enrolled into the Donepezil Treatment of Cognitive Impairment and Depression (DOTCODE) trial. High and low probability of OSA were defined as a STOP-Bang score of ≥5 (h-OSA) and of <5 (l-OSA), respectively.

Prediction of Relapse After Discontinuation of Antipsychotic Treatment in Alzheimer's Disease: The Role of Hallucinations.

Objective: In Alzheimer's disease, antipsychotic medications are often used for a period, with relief of symptoms, and then discontinued, after which relapse may occur. The authors sought to determine which neuropsychiatric symptoms predict relapse.

Method: In the Antipsychotic Discontinuation in Alzheimer's Disease trial, 180 patients with Alzheimer's disease and symptoms of agitation or psychosis were treated with risperidone for 16 weeks, after which patients who responded (N=110) were randomly assigned to continue risperidone for 32 weeks, to continue risperidone for 16 weeks followed by switch to placebo for 16 weeks, or to receive placebo for 32 weeks.

Heterogeneity of Treatment Response to Citalopram for Patients With Alzheimer's Disease With Aggression or Agitation: The CitAD Randomized Clinical Trial.

Objective: Pharmacological treatments for agitation and aggression in patients with Alzheimer's disease have shown limited efficacy. The authors assessed the heterogeneity of response to citalopram in the Citalopram for Agitation in Alzheimer Disease (CitAD) study to identify individuals who may be helped or harmed.

Method: In this double-blind parallel-group multicenter trial of 186 patients with Alzheimer's disease and clinically significant agitation, participants were randomly assigned to receive citalopram or placebo for 9 weeks, with the dosage titrated to 30 mg/day over the first 3 weeks.

Combined treatment with memantine/es-citalopram for older depressed patients with cognitive impairment: a pilot study.

Objective: The objective of the study is to assess combined antidepressant and memantine treatment in older patients presenting with depression and cognitive impairment.

Methods: Thirty-five depressed patients with cognitive impairment participated in this open-label pilot study. We evaluated whether, over a 48-week period, combined antidepressant (primarily es-citalopram) and memantine treatment was effective in the treatment of cognitive impairment and depression.

Change in agitation in Alzheimer's disease in the placebo arm of a nine-week controlled trial.

Background: Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).

Methods: In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks.

Time to Response to Citalopram Treatment for Agitation in Alzheimer Disease.

Objective: Agitation is a common and significant problem in Alzheimer disease (AD). In the recent Citalopram for Agitation in Alzheimer's Disease (CitAD) study, citalopram was efficacious for the treatment of AD agitation. Here we examined the time course and predictors of response to treatment.

An open treatment trial of duloxetine in elderly patients with dysthymic disorder.

Objective: We evaluated the efficacy and side effects of the selective serotonin and norepinephrine reuptake inhibitor antidepressant duloxetine in older adults with dysthymic disorder.

Methods: Patients ≥ 60 years old with dysthymic disorder received flexible dose duloxetine 20-120 mg daily in an open-label 12-week trial. The main outcomes were change from baseline to 12 weeks in 24-item Hamilton Depression Rating Scale scores and Treatment Emergent Symptoms Scale scores.

Changes in QTc interval in the citalopram for agitation in Alzheimer's disease (CitAD) randomized trial.

Background: A Food and Drug Administration (FDA) safety communication in August 2011 warned that citalopram was associated with a dose dependent risk of QT prolongation and recommended dose restriction in patients over the age of 60 but did not provide data for this age group.

Methods: CitAD was a randomized, double-masked, placebo-controlled, multicenter clinical trial for agitation in Alzheimer's disease (AD). Participants were assigned to citalopram (target dose of 30 mg/day) or placebo in a 1 ∶ 1 ratio.

Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial.

Importance: Agitation is common, persistent, and associated with adverse consequences for patients with Alzheimer disease. Pharmacological treatment options, including antipsychotics are not satisfactory.

Objective: The primary objective was to evaluate the efficacy of citalopram for agitation in patients with Alzheimer disease.

Donepezil treatment of older adults with cognitive impairment and depression (DOTCODE study): clinical rationale and design.

Treatment strategies for patients with depression and cognitive impairment (DEP-CI), who are at high risk to develop a clinical diagnosis of dementia, are not established. This issue is addressed in the donepezil treatment of cognitive impairment and depression (DOTCODE) pilot clinical trial. The DOTCODE study is the first long-term treatment trial that assesses differences in conversion to dementia and cognitive change in DEP-CI patients using a study design of open antidepressant medication plus add-on randomized, double-blind, placebo-controlled treatment with the acetylcholinesterase inhibitor donepezil.

Vascular depression: overrepresented among African Americans?

Objective: Our primary aim was to compare the rate of vascular depression among a clinical sample of African American and Caucasian depressed older adults. Secondary aims included characterizing the clinical and neuropsychological profile of vascular depression and comparing antidepressant response rates between patients with vascular and nonvascular depression.

Methods: This was a two-site, multi-ethnic, open 8-week trial of antidepressant medication in older adults with depression.

Antidepressant treatment of melancholia in older adults.

Objective: This is the first prospective trial in an outpatient sample comparing the effect of nortriptyline with sertraline in the treatment of depression with and without melancholia. We hypothesized that patients with melancholia would respond better to nortriptyline than sertraline, whereas among patients without melancholia, nortriptyline and sertraline would have equal efficacy.

Methods: We conducted a randomized 12-week trial comparing sertraline with nortriptyline in the treatment of patients with nonpsychotic, unipolar major depression stratified by the presence of melancholia.