Publications by authors named "Ronald Killiany"

Article Synopsis
  • The study explores a brain age prediction model for rhesus macaques using machine learning algorithms applied to neuroimaging data, aiming to determine their biological age and compare it to human brain aging.
  • Structural MRI data from 43 macaques were analyzed to create a comprehensive brain atlas, resulting in a model that predicts biological age with a correlation of 0.72 using 22 key features.
  • Key brain regions identified in the model, such as the Right Fronto-orbital Cortex and Right Frontal Pole, highlight similarities and differences in brain aging processes between non-human primates and humans.
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Introduction: Gulf War Illness (GWI), also called Chronic Multisymptom Illness (CMI), is a multi-faceted condition that plagues an estimated 250,000 Gulf War (GW) veterans. Symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. We previously reported that 12% of a convenience sample of middle aged (median age 52 years) GW veterans met criteria for mild cognitive impairment (MCI), a clinical syndrome most prevalent in older adults (e.

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The application of artificial intelligence (AI) to summarize a whole-brain magnetic resonance image (MRI) into an effective "brain age" metric can provide a holistic, individualized, and objective view of how the brain interacts with various factors (e.g., genetics and lifestyle) during aging.

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  • Researchers studied how white matter (WM) changes are linked to brain health and memory in people with Alzheimer's disease and related conditions.
  • They looked at 241 older participants, checking their brain scans and memory abilities to find differences in two important brain pathways.
  • The study found that the health of these brain pathways affects memory and brain structure, which could help us understand how Alzheimer's progresses.
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Article Synopsis
  • This study investigated the effectiveness of plasma glial fibrillary acidic protein (GFAP) as a biomarker for cognitive impairment in Alzheimer's disease (AD) compared to other biomarkers like neurofilament light chain (NfL) and phosphorylated tau (p-tau).
  • The research analyzed plasma samples from 567 participants and correlated GFAP levels with cognitive functions and dementia severity, finding that GFAP was significantly more effective in differentiating between normal cognition and AD dementia or mild cognitive impairment.
  • While higher GFAP levels were linked to worse cognitive performance and dementia symptoms, it specifically predicted memory decline over time but did not indicate progression to mild cognitive impairment or dementia.
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Introduction: The precise apolipoprotein E () ε4-specific molecular pathway(s) for Alzheimer's disease (AD) risk are unclear.

Methods: Plasma protein modules/cascades were analyzed using weighted gene co-expression network analysis (WGCNA) in the Alzheimer's Disease Neuroimaging Initiative study. Multivariable regression analyses were used to examine the associations among protein modules, AD diagnoses, cerebrospinal fluid (CSF) phosphorylated tau (p-tau), and brain glucose metabolism, stratified by genotype.

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Majority of dementia research is conducted in non-Hispanic White participants despite a greater prevalence of dementia in other racial groups. To obtain a better understanding of biomarker presentation of Alzheimer's disease (AD) in the non-Hispanic White population, this study exclusively examined AD biomarker abnormalities in 85 Black and/or African American participants within the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants were classified by the ADNI into 3 clinical groups: cognitively normal, mild cognitive impairment, or dementia.

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Background: Decision-making is essential to human functioning, and resolving uncertainty is an essential part of decision-making. Impaired decision-making is present in many pathological conditions, and identifying markers of decision-making under uncertainty will provide a measure of clinical impact in future studies of therapeutic intervention for impaired decision-making.

Objective: To describe EEG event-related potentials (ERPs) correlating with decision-making under uncertain conditions when compared with certain conditions.

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Age-related declines in cognitive abilities occur as early as middle-age in humans and rhesus monkeys. Specifically, performance by aged individuals on tasks of executive function (EF) and working memory (WM) is characterized by greater frequency of errors, shorter memory spans, increased frequency of perseverative responses, impaired use of feedback and reduced speed of processing. However, how aging precisely differentially impacts specific aspects of these cognitive functions and the distinct brain areas mediating cognition are not well understood.

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This study longitudinally examined participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who underwent a conversion in amyloid-beta (Aβ) status in comparison to a group of ADNI participants who did not show a change in amyloid status over the same follow-up period. Participants included 136 ADNI dementia-free participants with 2 florbetapir positron emission tomography (PET) scans. Of these participants, 68 showed amyloid conversion as measured on florbetapir PET, and the other 68 did not.

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Both the medial temporal lobe and the dorsolateral prefrontal cortex have been implicated in learning and memory. However, it has been difficult to ascertain the degree to which the two structures are dependent on each other or interact in subserving these cognitive functions. To investigate this question directly, we prepared two group of monkeys.

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Age-related declines in cognitive abilities occur as early as middle-age in humans and rhesus monkeys. Specifically, performance by aged individuals on tasks of executive function (EF) and working memory (WM) is characterized by greater frequency of errors, shorter memory spans, increased frequency of perseverative responses, impaired use of feedback and reduced speed of processing. However, how aging precisely differentially impacts specific aspects of these cognitive functions and the distinct brain areas mediating cognition are not well understood.

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Background: It remains unclear whether persistent loneliness is related to brain structures that are associated with cognitive decline and development of Alzheimer's disease (AD). This study aimed to investigate the relationships between different loneliness types, cognitive functioning, and regional brain volumes.

Methods: Loneliness was measured longitudinally, using the item from the Center for Epidemiologic Studies Depression Scale in the Framingham Heart Study, Generation 3, with participants' average age of 46·3 ± 8·6 years.

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Background: Carotid atherosclerosis is associated with cognitive impairment and dementia, though there is limited evidence of a direct link between carotid disease and amyloid-β (Aβ) burden.

Objective: We studied the association of baseline and progressive carotid intima media thickness (CIMT) with Aβ on 11C-Pittsburgh Compound B (PiB) to determine if those with carotid atherosclerosis would have higher Aβ burden.

Methods: We studied 47 participants from the Framingham Offspring cohort with carotid ultrasounds measuring CIMT at their 6th clinic examination (aged 49.

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Blood-based biomarkers such as tau phosphorylated at threonine 181 (phosphorylated-tau181) represent an accessible, cost-effective and scalable approach for the in vivo detection of Alzheimer's disease pathophysiology. Plasma-pathological correlation studies are needed to validate plasma phosphorylated-tau181 as an accurate and reliable biomarker of Alzheimer's disease neuropathological changes. This plasma-to-autopsy correlation study included participants from the Boston University Alzheimer's Disease Research Center who had a plasma sample analysed for phosphorylated-tau181 between 2008 and 2018 and donated their brain for neuropathological examination.

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Background And Objectives: Cerebrovascular disease (CBVD) is frequently comorbid with autopsy-confirmed Alzheimer disease (AD), but its contribution to the clinical presentation of AD remains unclear. We leveraged the National Alzheimer's Coordinating Center (NACC) uniform and neuropathology datasets to compare the cognitive and functional trajectories of AD+/CBVD+ and AD+/CBVD- brain donors.

Methods: The sample included NACC brain donors with autopsy-confirmed AD (Braak stage ≥3, score ≥2) and complete Uniform Data Set (UDS) evaluations between 2005 and 2019, with the most recent UDS evaluation within 2 years of autopsy.

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Aged-related declines in cognition, especially working memory and executive function, begin in middle-age and these abilities are known to be mediated by the prefrontal cortex (PFC) and more specifically the dopamine (DA) system within the PFC. In both humans and monkeys, there is significant evidence that the PFC is the first cortical region to change with age and the PFC appears to be particularly vulnerable to age-related loss of dopamine (DA). Therefore, the DA system is a strong candidate for therapeutic intervention to slow or reverse age related declines in cognition.

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Background: Chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy, cannot currently be diagnosed during life. Atrophy patterns on magnetic resonance imaging could be an effective in vivo biomarker of CTE, but have not been characterized. Mechanisms of neurodegeneration in CTE are unknown.

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Introduction: We examined the ability of plasma hyperphosphorylated tau (p-tau) to detect cognitive impairment due to Alzheimer's disease (AD) independently and in combination with plasma total tau (t-tau) and neurofilament light (NfL).

Methods: Plasma samples were analyzed using the Simoa platform for 235 participants with normal cognition (NC), 181 with mild cognitive impairment due to AD (MCI), and 153 with AD dementia. Statistical approaches included multinomial regression and Gaussian graphical models (GGMs) to assess a network of plasma biomarkers, neuropsychological tests, and demographic variables.

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Background And Objectives: Late neuropathologies of repetitive head impacts from contact sports can include chronic traumatic encephalopathy (CTE) and white matter degeneration. White matter hyperintensities (WMH) on fluid-attenuated inversion recovery (FLAIR) MRI scans are often viewed as microvascular disease from vascular risk, but might have unique underlying pathologies and risk factors in the setting of repetitive head impacts. We investigated the neuropathologic correlates of antemortem WMH in brain donors exposed to repetitive head impacts.

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Age-related impairments in cognitive function occur in multiple animal species including humans and nonhuman primates. Humans and rhesus monkeys exhibit a similar pattern of cognitive decline beginning in middle age, particularly within the domain of executive function. The prefrontal cortex is the brain region most closely associated with mediating executive function.

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The Boston University-based Gulf War Illness Consortium (GWIC) is a multidisciplinary initiative developed to provide detailed understanding of brain and immune alterations that underlie Gulf War illness (GWI), the persistent multisymptom disorder associated with military service in the 1990-1991 Gulf War. The core GWIC case-control clinical study conducted in-depth brain and immune evaluation of 269 Gulf War veterans (223 GWI cases, 46 controls) at three U.S.

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Background And Objectives: Previous research has shown that elevated blood C-reactive protein (CRP) is associated with increased Alzheimer disease (AD) risk only in ε4 allele carriers; the objective of this study was to examine the interactive effects of plasma CRP and genotype on cognition and AD biomarkers.

Methods: Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were analyzed, including genotype; plasma CRP concentrations; diagnostic status (i.e.

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The goal of this study was to investigate whether alterations in cerebral microvasculature, as measured by cerebral blood volume (CBV), contribute to age- and hypertension-related impairments in cognitive function with a focus on executive function and memory. Data were collected on 19 male rhesus monkeys ranging from 6.4 to 21.

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Background: Generative adversarial networks (GAN) can produce images of improved quality but their ability to augment image-based classification is not fully explored. We evaluated if a modified GAN can learn from magnetic resonance imaging (MRI) scans of multiple magnetic field strengths to enhance Alzheimer's disease (AD) classification performance.

Methods: T1-weighted brain MRI scans from 151 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI), who underwent both 1.

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