Publications by authors named "Michael A Yassa"

Importance: Subjective cognitive decline (SCD) may be an early indicator of Alzheimer disease and related dementias (ADRD), yet its association with plasma biomarkers remains unclear among middle-aged and older adults (aged 50-86 years).

Objective: To examine associations between plasma biomarkers of amyloid, tau, neuroaxonal damage, and glial activation with SCD in a heterogeneous cohort of Hispanic and/or Latino adults.

Design, Setting, And Participants: This cross-sectional study used survey-weighted data from the Study of Latinos-Investigation of Neurocognitive Aging, an ancillary study of the Hispanic Community Health Study/Study of Latinos.

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Unlabelled: The paraventricular nucleus of the thalamus (PVT) is an evolutionarily conserved midline thalamic structure known to contribute to arousal, interoceptive states, and motivated behaviors. Yet, a consensus anatomical definition of the human PVT across tissue-based and MRI-based approaches remains elusive, thereby limiting reliable translation between its cellular characteristics and in vivo functional connectivity. To address this challenge, we describe a histologically-informed PVT segmentation compatible with standard 3T MR imaging pipelines.

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Background: Amyloid beta (Aβ) plaque burden, as measured by positron emission tomography (PET), is increasingly being used as a biomarker for Alzheimer's disease (AD) as well as a screening or monitoring tool for clinical trials with amyloid-lowering drugs. However, PET imaging is expensive, invasive and not widely available for all patients, necessitating alternative means to assess brain Aβ accumulation.

Objectives: In this study, we measured levels of Aβ42, Aβ40 and Aβ38 in saliva samples from cognitively unimpaired older adults (n=93; 61.

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Study Objectives: Memory consolidation during non-rapid eye movement slow wave sleep (NREM SWS) involves reactivation of a hippocampal index which integrates distributed cortical representations of an experience. This study examined whether individual differences in brain network properties that align with this theoretical organization were associated with interindividual variability in memory consolidation during sleep.

Methods: Thirty-six older adults (μage=72.

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Background And Objectives: Cerebral small vessel disease (CSVD) is a leading cause of cognitive decline and functional loss in older adults. Obstructive sleep apnea (OSA) is common in older adults, can increase cerebrovascular disease risk, and is linked to medial temporal lobe (MTL) degeneration and cognitive impairment. However, the interaction between OSA features and CSVD burden and their combined effect on MTL structure and function are not well understood.

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Cerebral amyloid-beta (Aβ) accumulation, a hallmark pathology of Alzheimer's disease (AD), precedes clinical impairment by two to three decades. However, it is unclear whether Aβ contributes to subtle memory deficits observed during the preclinical stage. The heterogeneous emergence of Aβ deposition may selectively impact certain memory domains, which rely on distinct underlying neural circuits.

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Preserving the ability to vividly recall emotionally rich experiences contributes to quality of life in older adulthood. While prior works suggest that moderate-intensity physical activity (MPA) may bolster memory, it is unclear whether this extends to emotionally salient memories consolidated during sleep. In the current study, older adults (mean age = 72.

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Article Synopsis
  • By age 40, over 90% of adults with Down syndrome develop Alzheimer’s disease, with many progressing to dementia, despite having few typical vascular risk factors.
  • This study analyzed how small vessel cerebrovascular disease impacts Alzheimer's disease progression and neurodegeneration in adults with Down syndrome, using MRI and plasma biomarker data from 185 participants.
  • Results indicated a complex relationship where white matter hyperintensity (WMH) levels influenced phosphorylated tau, linked by glial fibrillary acidic protein, suggesting that cerebrovascular health affects Alzheimer’s pathology in this population.
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Background: Unpredictable childhood experiences are an understudied form of early life adversity that impacts neurodevelopment in a sex-specific manner. The neurobiological processes by which exposure to early-life unpredictability impacts development and vulnerability to psychopathology remain poorly understood. The present study investigates the sex-specific consequences of early-life unpredictability on the limbic network, focusing on the hippocampus and the amygdala.

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Cerebral amyloid-beta (Aβ) accumulation, a hallmark pathology of Alzheimer's disease (AD), precedes clinical impairment by two to three decades. However, it is unclear whether Aβ contributes to subtle memory deficits observed during the preclinical stage. The heterogenous emergence of Aβ deposition may selectively impact certain memory domains, which rely on distinct underlying neural circuits.

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The amyloid beta (Aβ) 42/40 ratio has been widely studied as a biomarker in Alzheimer's disease (AD); however, other Aβ peptides could also represent relevant biomarkers. We measured levels of Aβ38/40/42 in plasma samples from cognitively-unimpaired older adults and determined the relationships between Aβ levels and amyloid positron-emission-tomography (PET) and performance on a learning and memory task. We found that all Aβ peptides individually and the Aβ42/40 ratio, but not the Aβ42/38 ratio, were significantly correlated with brain amyloid (Aβ-PET).

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Background: Anhedonia stands as a life-threatening transdiagnostic feature of many mental illnesses, most notably major depression and involves neural circuits for processing reward information. The paraventricular nucleus of the thalamus (PVT) is associated with reward-seeking behavior, however, links between the PVT circuit and anhedonia have not been investigated in humans.

Methods: In a sample of adults with and without psychiatric symptoms (n = 75, 18-41 years, 55 female), we generated an anhedonia factor score for each participant using a latent factor analysis, utilizing data from depression and anxiety assessments.

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Age-related structural brain changes may be better captured by assessing complex spatial geometric differences rather than isolated changes to individual regions. We applied a novel analytic method to quantify age-related changes to the spatial anatomy of the brain by measuring expansion and compression of global brain shape and the distance between cross-hemisphere homologous regions. To test how global brain shape and regional distances are affected by aging, we analyzed 2,603 structural MRIs (range: 30-97 years).

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Adults with Down syndrome are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease and is linked to a diagnosis of dementia in adults with Down syndrome via structural imaging markers of cerebrovascular disease and atrophy.

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UK Biobank is a large-scale epidemiological resource for investigating prospective correlations between various lifestyle, environmental, and genetic factors with health and disease progression. In addition to individual subject information obtained through surveys and physical examinations, a comprehensive neuroimaging battery consisting of multiple modalities provides imaging-derived phenotypes (IDPs) that can serve as biomarkers in neuroscience research. In this study, we augment the existing set of UK Biobank neuroimaging structural IDPs, obtained from well-established software libraries such as FSL and FreeSurfer, with related measurements acquired through the Advanced Normalization Tools Ecosystem.

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Introduction: Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimer's disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late-onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS.

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Obstructive sleep apnea (OSA) is common in older adults and is associated with medial temporal lobe (MTL) degeneration and memory decline in aging and Alzheimer's disease (AD). However, the underlying mechanisms linking OSA to MTL degeneration and impaired memory remains unclear. By combining magnetic resonance imaging (MRI) assessments of cerebrovascular pathology and MTL structure with clinical polysomnography and assessment of overnight emotional memory retention in older adults at risk for AD, cerebrovascular pathology in fronto-parietal brain regions was shown to statistically mediate the relationship between OSA-related hypoxemia, particularly during rapid eye movement (REM) sleep, and entorhinal cortical thickness.

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Enhanced memory for emotional experiences is hypothesized to depend on amygdala-hippocampal interactions during memory consolidation. Here we show using intracranial recordings from the human amygdala and the hippocampus during an emotional memory encoding and discrimination task increased awake ripples after encoding of emotional, compared to neutrally-valenced stimuli. Further, post-encoding ripple-locked stimulus similarity is predictive of later memory discrimination.

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Episodic memory arises as a function of dynamic interactions between the hippocampus and the neocortex, yet the mechanisms have remained elusive. Here, using human intracranial recordings during a mnemonic discrimination task, we report that 4-5 Hz (theta) power is differentially recruited during discrimination vs. overgeneralization, and its phase supports hippocampal-neocortical when memories are being formed and correctly retrieved.

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Importance: By age 40 years over 90% of adults with Down syndrome (DS) have Alzheimer's disease (AD) pathology and most progress to dementia. Despite having few systemic vascular risk factors, individuals with DS have elevated cerebrovascular disease (CVD) markers that track with the clinical progression of AD, suggesting a role for CVD that is hypothesized to be mediated by inflammatory factors.

Objective: To examine the pathways through which small vessel CVD contributes to AD-related pathophysiology and neurodegeneration in adults with DS.

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Individuals with Down syndrome (DS) are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease, entorhinal cortical atrophy, and diagnosis of dementia in adults with DS.

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UK Biobank is a large-scale epidemiological resource for investigating prospective correlations between various lifestyle, environmental, and genetic factors with health and disease progression. In addition to individual subject information obtained through surveys and physical examinations, a comprehensive neuroimaging battery consisting of multiple modalities provides imaging-derived phenotypes (IDPs) that can serve as biomarkers in neuroscience research. In this study, we augment the existing set of UK Biobank neuroimaging structural IDPs, obtained from well-established software libraries such as FSL and FreeSurfer, with related measurements acquired through the Advanced Normalization Tools Ecosystem.

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Memory consolidation occurs via reactivation of a hippocampal index during non-rapid eye movement slow-wave sleep (NREM SWS) which binds attributes of an experience existing within cortical modules. For memories containing emotional content, hippocampal-amygdala dynamics facilitate consolidation over a sleep bout. This study tested if modularity and centrality-graph theoretical measures that index the level of segregation/integration in a system and the relative import of its nodes-map onto central tenets of memory consolidation theory and sleep-related processing.

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Alzheimer's disease (AD) is the most common type of dementia, characterized by early memory impairments and gradual worsening of daily functions. AD-related pathology, such as amyloid-beta (Aβ) plaques, begins to accumulate many years before the onset of clinical symptoms. Predicting risk for AD via related pathology is critical as the preclinical stage could serve as a therapeutic time window, allowing for early management of the disease and reducing health and economic costs.

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