A major challenge in the development of more effective therapeutic strategies for Alzheimer's disease (AD) is the identification of molecular mechanisms linked to specific pathophysiological features of the disease. Importantly AD has a two-fold higher incidence in women than men and a protracted prodromal phase characterized by amnestic mild-cognitive impairment (aMCI) suggesting that biological processes occurring early can initiate vulnerability to AD. Here, we used a sample of 125 subjects from two independent study cohorts to determine the levels in plasma (the most accessible specimen) of two essential mitochondrial markers acetyl-L-carnitine (LAC) and its derivative free-carnitine motivated by a mechanistic model in rodents in which targeting mitochondrial metabolism of LAC leads to the amelioration of cognitive function and boosts epigenetic mechanisms of gene expression.
View Article and Find Full Text PDFIntroduction: Depression is frequent among older adults and is a risk factor for dementia. Identifying molecular links between depression and dementia is necessary to shed light on shared disease mechanisms. Reduced brain-derived neurotrophic factor (BDNF) and neuroinflammation are implicated in the pathophysiology of depression and dementia.
View Article and Find Full Text PDFAge increases the risk for cognitive impairment and is the single major risk factor for Alzheimer's disease (AD), the most prevalent form of dementia in the elderly. The pathophysiological processes triggered by aging that render the brain vulnerable to dementia involve, at least in part, changes in inflammatory mediators. Here we show that lipoxin A4 (LXA4), a lipid mediator of inflammation resolution known to stimulate endocannabinoid signaling in the brain, is reduced in the aging central nervous system.
View Article and Find Full Text PDFAttention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent neurodevelopmental condition, which may be associated with life-enduring cognitive dysfunction. It has been hypothesized that age-related cognitive decline may overlap with preexisting deficits in older ADHD patients, leading to increased problems to manage everyday-life activities. This phenomenon may mimic neurodegenerative disorders, in particular Mild Cognitive Impairment (MCI).
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) and Lewy body disease (LBD) are complex neurodegenerative disorders that have been associated with brain inflammation and impaired neurotransmission.
Objective: We aimed to determine concentrations of multiple cytokines, chemokines, and neurotransmitters previously associated with brain inflammation and synapse function in cerebrospinal fluid (CSF) from AD and LBD patients.
Methods: We examined a panel of 50 analytes comprising neurotransmitters, cytokines, chemokines, and hormones in CSF in a cohort of patients diagnosed with mild cognitive impairment (MCI), AD, LBD, or non-demented controls (NDC).
Previous research investigating language in attention-deficit hyperactivity disorder (ADHD) has demonstrated several deficits in many aspects. However, no previous study employed quantitative methodology providing objective measures that could be compared among different studies with diverse samples. To fill this gap, we used network analysis to investigate how ADHD symptomatology impacts narrative discourse, a complex linguistic task considered to be an ecological measure of language.
View Article and Find Full Text PDFObjectives: Anosognosia is the inability to recognize one's own symptoms. Although dementia with Lewy bodies (DLB) is the second most common degenerative dementia, there is little evidence of memory deficit awareness in this condition. The objectives of this research were to compare anosognosia between individuals with DLB and dementia due to Alzheimer's disease (AD) and to evaluate whether medial temporal atrophy, a marker of AD pathology, could help to explain different rates of anosognosia in DLB and dementia due to AD.
View Article and Find Full Text PDFIntroduction: Irisin is a novel hormone originally identified for its role as a regulator of peripheral metabolism and recently found to protect synapses and rescue memory in mouse models of Alzheimer's disease (AD). However, whether and how cerebrospinal fluid (CSF) irisin varies in relation to canonical AD biomarkers and cognition in humans remains unknown.
Methods: We determined CSF levels of irisin and brain-derived neurotrophic factor (BDNF) and examined their correlations with CSF amyloid beta (Aβ), total tau, and Mini-Mental State Exam (MMSE) scores in a cohort comprising AD patients ( = 14) and non-demented controls (NDC; = 25).
Background: Narrative discourse (ND) refers to one's ability to verbally reproduce a sequence of temporally and logically-linked events. Impairments in ND may occur in subjects with Amnestic Mild Cognitive Impairment (aMCI) and Alzheimer's Disease (AD), but correlates across this function, neuroimaging and cerebrospinal fluid (CSF) AD biomarkers remain understudied.
Objectives: We sought to measure correlates among ND, Diffusion Tensor Imaging (DTI) indexes and AD CSF biomarkers in patients within the AD spectrum.
Background: Episodic memory impairments have been described as initial clinical findings in the Alzheimer's Disease (AD) spectrum, which could be associated with the presence of early hippocampal dysfunction. However, correlates between performances in neuropsychological tests and hippocampal volumes in AD were inconclusive in the literature. Divergent methods to assess episodic memory have been depicted as a major source of heterogeneity across studies.
View Article and Find Full Text PDFUnlabelled: The Von Restorff (isolation) effect refers to a stimulus that is more likely to be remembered amongst other stimuli in memory tasks. It has been demonstrated with different age ranges and methodologies.
Objective: To investigate: a) the presence of the isolation effect in elders tested with the new Brazilian Portuguese version of the Rey Auditory Verbal Learning Task (RAVLT) in which a word with potential emotional weight (mother) was introduced; b) whether isolation effects persist in memory disorders of different degrees of severity (Mild Cognitive Impairment [MCI]; Alzheimer's Dementia [AD]).
Background: Metabolic Syndrome (MetS) refers to a cluster of metabolic disturbances which is associated with increased risk for vascular and degenerative conditions in general population. Although the relationship between vascular risk factors and dementia is undisputable, additional hazard for cognitive decline in older population with concurrent metabolic disorders still waits to be demonstrated. The present review aims to analyze data on MetS and risk for cognitive decline in elderly persons.
View Article and Find Full Text PDFObjective: To investigate whether the level of awareness of memory deficits is useful for discriminating between major depressive disorder (MDD) and mild cognitive impairment (MCI) in the elderly.
Methods: Sixty-three consecutively referred patients (38 women and 25 men) with memory concerns comprising three groups (clinical control, MDD and MCI) underwent a memory test (Rey Auditory Verbal Learning Test [RAVLT]) and completed the Memory Assessment Complaints-Questionnaire (MAC-Q). Level of awareness was estimated by the difference between the MAC-Q score and the score on the fifth presentation of the RAVLT.
Language batteries used to assess the skills of elderly individuals, such as naming and semantic verbal fluency, present some limitations in differentiating healthy controls from patients with amnestic mild cognitive impairment (a-MCI). Deficits in narrative discourse occur early in dementia caused by Alzheimer's disease (AD), and the narrative discourse abilities of a-MCI patients are poorly documented. The present study sought to propose and evaluate parameters for investigating narrative discourse in these populations.
View Article and Find Full Text PDFBackground: Prose memory tests exhibit ecological validity, but the influence of non-memory functions on immediate recall in elderly subjects with memory complaints has not been fully investigated. This study examined (1) whether the ability to immediately recall a story can distinguish among clinical controls, amnesic mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD) and (2) which cognitive functions contribute to immediate recall performance.
Methods: A total of 73 consecutive volunteers (50 women and 23 men) aged 47-88 (mean age = 71.