Exploring mitochondrial blood-based and genetic markers in older adults with mild cognitive impairment and remitted major depressive disorder.

Mild cognitive impairment (MCI) is a prodromal stage in aging to possible progression to Alzheimer's disease and related dementia (ADRD), where co-occurrence of major depressive disorder (MDD) accelerates the progression. Metabolic and mitochondrial abnormalities in ADRD and other neurodegenerative disorders have been widely suggested, while possible mitochondrial dysfunction has been associated with etiopathology of both MCI and MDD. Hence, investigation of mitochondrial markers in MCI, MDD, and presence of both conditions is warranted.

The associations among glycemic control, heart variability, and autonomic brain function in healthy individuals: Age- and sex-related differences.

Introduction: The purpose of this study was to clarify the relationships between glycemia and function of the autonomic nervous system (ANS), assessed via resting-state functional connectivity (FC) and heart-rate variability (HRV).

Methods: Data for this study were extracted from the Leipzig Study for Mind-Body-Emotion Interactions, including 146 healthy adults (114 young, 32 older). Variables of interest were glycated hemoglobin (HbA1c), resting-state FC in the salience aspect of the central-autonomic (S-CAN) and salience network (SN) and HRV (RMSSD and high-frequency HRV (HF-HRV)).

Cognitive Profiles in Treatment-Resistant Late-Life Depression and Their Impact on Treatment Outcomes.

Background: Late-life depression (LLD) is associated with cognitive impairment, but substantial heterogeneity exists among patients. Data on the extent of cognitive impairments are inconclusive, particularly in patients with treatment-resistant depression (TRD). We investigated the cognitive profiles of patients with treatment-resistant versus nonresistant LLD and aimed to identify distinct cognitive subgroups.

The utility of remote cognitive screening tools in identifying cognitive impairment in older surgical patients: An observational cohort study.

Study Objectives: To determine the prevalence of suspected cognitive impairment using the Centers for Disease Control and Prevention (CDC) cognitive question, Ascertain Dementia Eight-item Questionnaire (AD8), Modified Telephone Interview for Cognitive Status (TICS-M), and Telephone Montreal Cognitive Assessment (T-MoCA), the agreement between each tool beyond chance, and the risk factors associated with a positive screen.

Design: Multicenter prospective study.

Setting: Remote preoperative assessments.

Neurophysiological and other features of working memory in older adults at risk for dementia.

Unlabelled: Theta-gamma coupling (TGC) is a neurophysiological process that supports working memory. Working memory is associated with other clinical and biological features. The extent to which TGC is associated with these other features and whether it contributes to working memory beyond these features is unknown.

Cognitive function based on theta-gamma coupling vs. clinical diagnosis in older adults with mild cognitive impairment with or without major depressive disorder.

Whether individuals with mild cognitive impairment (MCI) and a history of major depressive disorder (MDD) are at a higher risk for cognitive decline than those with MCI alone is still not clear. Previous work suggests that a reduction in prefrontal cortical theta phase-gamma amplitude coupling (TGC) is an early marker of cognitive impairment. This study aimed to determine whether using a TGC cutoff is better at separating individuals with MCI or MCI with remitted MDD (MCI+rMDD) on cognitive performance than their clinical diagnosis.

Predictors of remission after repetitive transcranial magnetic stimulation for the treatment of late-life depression.

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment in patients with depression, yet treatment response remains variable. While previous work has identified predictors of remission in younger adults, relatively little data exists in late-life depression (LLD). To address this gap, data from 164 participants with LLD from a randomized non-inferiority treatment trial comparing standard bilateral rTMS to bilateral theta burst stimulation (TBS) (ClinicalTrials.

Heterogeneity of Cognition in Older Adults with Remitted Major Depressive Disorder: A Latent Profile Analysis.

Objectives: To identify data-driven cognitive profiles in older adults with remitted major depressive disorder (rMDD) with or without mild cognitive impairment (MCI) and examine how the profiles differ regarding demographic, clinical, and neuroimaging measures.

Design: Secondary cross-sectional analysis using latent profile analysis.

Setting: Multisite clinical trial in Toronto, Canada.

Age-Related Alterations in Gray Matter Microstructure in Older People With Remitted Major Depression at Risk for Dementia.

Background: Major depressive disorder (MDD) in late life is a risk factor for mild cognitive impairment (MCI) and Alzheimer's disease. However, studies of gray matter changes have produced varied estimates of which structures are implicated in MDD and dementia. Changes in gray matter volume and cortical thickness are macrostructural measures for the microstructural processes of free water accumulation and dendritic spine loss.

Beta to theta power ratio in EEG periodic components as a potential biomarker in mild cognitive impairment and Alzheimer's dementia.

Background: Alzheimer's dementia (AD) is associated with electroencephalography (EEG) abnormalities including in the power ratio of beta to theta frequencies. EEG studies in mild cognitive impairment (MCI) have been less consistent in identifying such abnormalities. One potential reason is not excluding the EEG aperiodic components, which are less associated with cognition than the periodic components.

Brain-Cognition Associations in Older Patients With Remitted Major Depressive Disorder or Mild Cognitive Impairment: A Multivariate Analysis of Gray and White Matter Integrity.

Background: Almost half of older patients with major depressive disorder (MDD) present with cognitive impairment, and one-third meet diagnostic criteria for mild cognitive impairment (MCI). However, mechanisms linking MDD and MCI remain unclear. We investigated multivariate associations between brain structural alterations and cognition in 3 groups of older patients at risk for dementia, remitted MDD (rMDD), MCI, and rMDD+MCI, as well as cognitively healthy nondepressed control participants.

Lipopolysaccharide, Immune Biomarkers and Cerebral Amyloid-Beta Deposition in Older Adults With Mild Cognitive Impairment & Major Depressive Disorder.

Objective: Inflammatory activation and increased immune response to lipopolysaccharide occur in both depression and cognitive decline and may link these two conditions. We investigated whether lipopolysaccharide (LPS), LPS binding protein (LBP) and peripheral biomarkers of immune response were associated with increased cerebral deposition of amyloid-beta (Abeta) in older adults with mild cognitive impairment (MCI) and remitted major depressive disorder (rMDD).

Design: Cross-sectional analysis.

Sex Modifies the Associations of APOEɛ4 with Neuropsychiatric Symptom Burden in Both At-Risk and Clinical Cohorts of Alzheimer's Disease.

Background: Recent work suggests that APOEɛ4/4 females with Alzheimer's disease (AD) are more susceptible to developing neuropsychiatric symptoms (NPS).

Objective: To examine the interaction of sex and APOEɛ4 status on NPS burden using two independent cohorts: 1) patients at risk for AD with mild cognitive impairment and/or major depressive disorder (n = 252) and 2) patients with probable AD (n = 7,261).

Methods: Regression models examined the interactive effects of sex and APOEɛ4 on the number of NPS experienced and NPS Severity.

Self- versus informant-report of cognitive decline in mild cognitive impairment: Concordance with cognitive and functional performance.

Objective: Debate continues regarding the use of self- versus informant-report to diagnose mild cognitive impairment (MCI) with studies reporting patients both overestimating and underestimating their abilities relative to informants. We assessed concordance of self- versus informant-report of cognitive decline with objective cognitive and functional performance in the participants of the preventing Alzheimer's dementia with cognitive remediation plus transcranial direct current stimulation in mild cognitive impairment and depression randomized controlled trial (PACt-MD).

Method: Three hundred six participants with MCI, and their informants, reported on cognitive decline; the participants also completed a comprehensive assessment of objective cognitive and functional performance.

Cognitive control, interference inhibition, and ordering of information during working memory in younger and older healthy adults.

Investigating effects of aging on neurophysiological mechanisms underlying working memory provides a better understanding of potential targets for brain intervention to prevent cognitive decline. Theta-gamma coupling (TGC) indexes the ability to order information processed during working memory tasks. Frontal theta event-related synchronization (ERS) and parietal alpha event-related desynchronization (ERD) index cognitive control and interference inhibition, respectively.

Association of functional connectivity of the executive control network or default mode network with cognitive impairment in older adults with remitted major depressive disorder or mild cognitive impairment.

Major depressive disorder (MDD) is associated with an increased risk of developing dementia. The present study aimed to better understand this risk by comparing resting state functional connectivity (rsFC) in the executive control network (ECN) and the default mode network (DMN) in older adults with MDD or mild cognitive impairment (MCI). Additionally, we examined the association between rsFC in the ECN or DMN and cognitive impairment transdiagnostically.

Time setting errors in the Clock Drawing Test are associated with both semantic and executive deficits.

The common requirement to set the time to "10 past 11" on the Clock Drawing Test is intended to elicit a stimulus bound response (SBR), in which the responder is "pulled" to the salient stimulus "10," resulting in hands set at "10 before 11." SBRs are considered markers of executive dysfunction, although this assumption has not yet been validated. We compared SBR and other time-setting errors on inhibitory control tests, hypothesizing that they represent related constructs.

Assessing the Longitudinal Relationship between Theta-Gamma Coupling and Working Memory Performance in Older Adults.

Theta-gamma coupling (TGC) is a neurophysiologic mechanism that supports working memory (WM). TGC is associated with N-back performance, a WM task. Similar to TGC, theta and alpha event-related synchronization (ERS) and desynchronization (ERD) are also associated with WM.

Primary Progressive Aphasia Presenting With Neuropsychiatric Symptoms.

We describe a case of primary progressive aphasia (PPA) with an underlying neurodegenerative motor disorder (possible ALS or PSP), presenting with symptoms of irritability and frustration, that were misdiagnosed and treated as a primary psychiatric disorder, i.e. depression.

Prefrontal GABA Levels Correlate with Memory in Older Adults at High Risk for Alzheimer's Disease.

γ-Aminobutyric acid (GABA), a primary inhibitory neurotransmitter in the brain, plays a significant role in aging and in neurodegenerative disorders, including Alzheimer's disease (AD). We investigated the relationship between GABA levels in the dorsomedial/dorsoanterolateral prefrontal cortex (DM/DA-PFC) and memory in high-AD risk participants. Thirty-eight participants (14 Cognitively Normal [CN], 11 with Subjective Cognitive Decline (SCD), and 13 Mild Cognitive Impairment [MCI]) underwent magnetic resonance spectroscopy at 3 Tesla.

Increased exhalation to inhalation ratio during breathing enhances high-frequency heart rate variability in healthy adults.

Heart rate variability (HRV) is a well-established surrogate of cardiac and emotional health that reflects the balance between sympathetic and parasympathetic activity of the autonomic nervous system. We examined the impact of manipulating exhalation to inhalation ratio (E:I) on HRV, without altering the intrinsic breathing rate of healthy individuals. We hypothesized that a longer exhalation relative to inhalation (E:I > 1) would shift HRV metrics in a direction consistent with increased parasympathetic activity.