Suzanne Craft

• University of Washington

INTRODUCTION: Dementia is a disabling condition that progressively impairs daily function. Timely identification of older adults at high risk for dementia or cognitive impairment (a potential precursor) is critical to maximizing opportunities for intervention. METHODS: Utilizing structured electronic health record data from 122,633 patients aged 55...

Non-human primates (NHPs) serve as critical models for understanding human brain function and neurological disorders due to their close evolutionary relationship with humans. Accurate brain tissue segmentation in NHPs is critical for understanding neurological disorders, but challenging due to the scarcity of annotated NHP brain MRI datasets, the s...

INTRODUCTION Diet quality mediates aging‐related risks of cognitive decline, neurodegeneration, and Alzheimer's disease (AD) through poorly defined mechanisms. METHODS The effects of diet on the presynaptic proteome of the temporal cortex were assessed in 36 female cynomolgus macaques randomized to Mediterranean or Western diets for 31 months. Ass...

Introduction: Stark disparities exist in the prevalence of Alzheimer’s disease (AD) and related dementias (ADRD) by social determinants of health (SDoH). Limited research is available on associations of SDoH with AD/ADRD biomarkers. This study aims to assess the impact of SDoH measures on ADRD-associated neuroimaging and plasma biomarkers. Hypothes...

INTRODUCTION Little is known about how Alzheimer’s disease (AD) plasma biomarkers relate to cerebral small vessel disease (cSVD) neuroimaging biomarkers. METHODS The study involved 251 Wake Forest Multi-Ethnic Study of Atherosclerosis (MESA) Exam 6 participants with plasma AD biomarkers, MRI, amyloid PET, and adjudicated cognitive status. Multivar...

INTRODUCTION: Studies suggest excellent performance of plasma p-tau217 for detecting amyloid pathology, though studies in more diverse populations are needed to validate previously determined cutpoints. METHODS: Plasma p-tau217 utility for detecting amyloid pathology (Aβ) via amyloid PET (n=598) and/or cerebrospinal fluid (CSF; n=154) was assessed...

Extracellular vesicles (EVs) have emerged as novel blood‐based biomarkers for various pathologies. The development of methods to enrich cell‐specific EVs from biofluids has enabled us to monitor difficult‐to‐access organs, such as the brain, in real time without disrupting their function, thus serving as liquid biopsy. Burgeoning evidence indicates...

Background Video interfacing is increasingly being used in research and health care. The ‘VCog’ Study seeks to determine whether remote research cognitive assessments are reliable and valid by directly comparing results from in‐person administration of a standardized cognitive battery to the same battery administered remotely by video. The study al...

Introduction Over 9 million Americans are projected to have dementia by 2030, and adults with mild cognitive impairment (MCI), a potential pre‐cursor to dementia, will also rise. With recent and emerging clinical trial evidence for interventions to slow the progression of MCI to dementia, identification of persons in primary care with undiagnosed e...

Background Cardiometabolic disorders are emerging risk factors for Alzheimer's disease (AD) and AD‐related dementia (ADRD). There is currently insufficient understanding of how different cardiometabolic profiles and blood biomarkers impact different AD‐related brain pathology regionally. This project uses data‐driven approaches and explainable arti...

Background Neuropsychiatric symptoms (NPS) in the Alzheimer’s Disease (AD) clinical spectrum are common, yet the pathological underpinnings are unclear. Prior research has been inconsistent, attributed in part to concomitant co‐pathologies. Additionally, prior modeling approaches have disregarded the distributional properties of right‐skewed NPS da...

Background Older vervet monkeys are an excellent model for studying age‐associated Aß deposition; however, they have high proportions of low‐affinity Aß sites compared to human brains. Commonly used Aß PET radiotracers are most useful in detecting high affinity Aß fibrils. Measuring real‐time levels of low affinity Aß fibrils through PET provides c...

Background Little is known about how plasma Alzheimer’s disease (AD) biomarkers relate to neuroimaging biomarkers of cerebral small vessel disease (cSVD) in the context of neurodegeneration and AD pathology in late life. Method This cross‐sectional study included 251 Multi‐Ethnic Study of Atherosclerosis (MESA) Exam 6 participants with plasma AD b...

Background Brains affected by Alzheimer’s disease (AD) exhibit senile plaques containing amyloid beta (Aß) peptides and neurofibrillary tangles, formed when tau becomes hyperphosphorylated and disengages from microtubules (MTs). Early instability in MTs is observed in the AD process, emphasizing its significance in connecting the hallmark pathologi...

Background Insulin resistance (IR) is associated with abnormal tau‐phosphorylation and IR markers in AD brain co‐localize with neurofibrillary tangles. One strategy to overcome brain IR is to increase brain insulin is via intranasal insulin (INI) administration using specialized intranasal devices that deliver insulin to the brain. Our recent INI v...

Background Adverse social exposome (indexed by high national Area Deprivation Index [ADI]) is linked to structural inequities and increased risk of clinical dementia diagnosis, yet linkage to ADRD neuropathology remains largely unknown. Early work from single site brain banks suggests a relationship, but assessment in large national cohorts is need...

Background Apathy in Alzheimer’s disease improves with methylphenidate (MPH) but treatment response was found to vary depending on clinical factors. Here, we explored whether underlying biological factors assessed by blood‐based biomarkers of neurodegeneration, inflammation and oxidative stress affect apathy treatment response. Method A subset of...

Background Although associated with early changes in Aβ and tau formations, microtubule (MT) destabilization has not yet been systematically evaluated as an early biomarker of neurodegeneration and a tool to quantify it in real‐time could provide information on these early changes in AD cascade. While current Aβ and tau PET approaches can character...

Background Brains affected by Alzheimer's disease (AD) exhibit senile plaques containing amyloid beta (Aβ) peptides and neurofibrillary tangles, formed when tau becomes hyperphosphorylated and disengages from microtubules (MTs). Early instability in MTs is observed in the AD process, emphasizing its significance in connecting the hallmark pathologi...

Background The Alzheimer’s Disease Center Fluid Biomarker (ADCFB) Initiative samples are analyzed centrally at NCRAD for AD plasma biomarkers. When combining NACC accessible data from across centers, biofluid biomarker data must be evaluated carefully. This will become more critical with the implementation of disease modifying therapies. Methods B...

Background Cardiometabolic disorders are emerging risk factors for Alzheimer's disease (AD) and AD‐related dementia (ADRD). There is currently insufficient understanding of how different cardiometabolic profiles and blood biomarkers impact different AD‐related brain pathology regionally. This project uses data‐driven approaches and explainable arti...

Background Adverse social exposome (indexed by national Area Deprivation Index [ADI] 80‐100 or ‘high ADI’) is linked to structural inequities and increased risk of Alzheimer’s disease neuropathology. Twenty percent of the US population resides within high ADI areas, predominantly in inner cities, tribal reservations and rural areas. The percentage...

Background Alzheimer’s disease (AD) is a neurodegenerative disorder with significant environmental factors, including diet, that influence its onset and progression. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored the KD’s molecular impact for markers...

Background Uniform manifold approximation and projection (UMAP) is a technique for dimension reduction and visualization of high‐dimensional (HD) data. Here, we apply UMAP to represent in two dimensions, data from members of the Wake Forest School of Medicine Alzheimer’s Disease Research Center (WFUSM‐ADRC) clinical cohort. Methods We examined bas...

Background Little is known about how plasma Alzheimer’s disease (AD) biomarkers relate to neuroimaging biomarkers of cerebral small vessel disease (cSVD) in the context of neurodegeneration and AD pathology in late life. Method This cross‐sectional study included 251 Multi‐Ethnic Study of Atherosclerosis (MESA) Exam 6 participants with plasma AD b...

Background Insulin resistance (IR) is associated with abnormal tau‐phosphorylation and IR markers in AD brain co‐localize with neurofibrillary tangles. One strategy to overcome brain IR is to increase brain insulin is via intranasal insulin (INI) administration using specialized intranasal devices that deliver insulin to the brain. Our recent INI v...

Background Insulin signaling deregulation in the brain is a critical risk factor for Alzheimer's disease (AD); however, molecular changes in this pathway during AD pathogenesis cannot be currently accessed in clinical setting due to lack of brain tissues. Here, we propose small extracellular vesicles (sEV) characterization as a non‐invasive approac...

Background Early autonomic function changes in Alzheimer’s disease (AD) may represent a biomarker for early affective changes in prodromal disease. We report preliminary differences in metrics of heart rate variability (HRV) before and during routine cognitive testing. Method We enrolled 50 participants from the Wake Forest Alzheimer’s Disease Res...

Background Alzheimer’s disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear. Method In this post-hoc analysis...

Background Diet composition is associated with neurodegenerative disease risk including Alzheimer’s Disease (AD). The adverse effects of Western‐style diets may be moderated, in part, by systemic as well as central inflammation, whereas the neuroprotective effects of Mediterranean diets may work through mechanisms that promote anti‐inflammatory phe...

Background Apathy in Alzheimer’s disease (AD) is associated with cognitive impairment, particularly executive functions such as selective attention, making it unclear whether apathy should be a separate treatment target. Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) is the largest and most recent trial assessing apathy and cognition. This an...

Background Neuropsychiatric symptoms (NPS) in the Alzheimer’s Disease (AD) clinical spectrum are common, yet the pathological underpinnings are unclear. Prior research has been inconsistent, attributed in part to concomitant co‐pathologies. Additionally, prior modeling approaches have disregarded the distributional properties of right‐skewed NPS da...

Background Vascular‐based dementia risk scores (VDRS) which reliably predict risk of Alzheimer’s disease and related dementias (ADRDs), may be useful to identify at‐risk individuals for secondary prevention trials. Dementia risk scores have typically focused on predicting ADRD‐associated symptoms, with fewer studies assessing capacity for detecting...

Background Western and Mediterranean diets differentially affect cerebral cortical gene expression, brain structure, and socioemotional behavior in middle‐aged female nonhuman primates (NHP) (Macaca fascicularis). In this study, we investigate the effect of diet on brain molecular composition. Method Using a machine learning approach, we quantifie...

Background Mediterranean diets may reduce Alzheimer’s disease (AD) risk and preserve cognitive function relative to Western diets by protecting against inflammation. In a long term controlled randomized trial of Mediterranean vs. Western diet consumption in cynomolgus macaques (Macaca fascicularis), difficult to conduct in humans, we found signific...

We previously showed peripheral blood mononuclear cell (PBMC) and platelet mitochondrial bioenergetic capacities are lower in older adults with Alzheimer’s disease (AD), with notable changes in fatty acid oxidation (FAO)-mediated respiration. The metabolic pathways underlying mitochondrial functional differences remain un-identified. This study inv...

Alzheimer’s disease (AD) dementia associates with systemic mitochondrial bioenergetic decline. We previously showed blood cell mitochondrial bioenergetics recapitulates bioenergetic capacity of highly metabolically active organs like brain, liver, and skeletal muscles, and peripheral blood mononuclear cell (PBMC) mitochondrial function relates to b...

The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell‐mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in...

INTRODUCTION Neighborhood disadvantage may be an important determinant of cardiometabolic health and cognitive aging. However, less is known about relationships among individuals with mild cognitive impairment (MCI). METHODS The objective of this study is to investigate the relationship between neighborhood disadvantage measured by national Area D...

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer’s Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-di...

Background Older vervet monkeys are an excellent model for studying age‐associated Aβ deposition; however, they have high proportions of low‐affinity Aβ sites compared to human brains. Commonly used Aβ PET radiotracers are most useful in detecting high affinity Aβ fibrils. Measuring real‐time levels of low affinity Aβ fibrils through PET provides c...

Background RNA-binding proteins (RBPs) modulate the synaptic proteome and are instrumental in maintaining synaptic homeostasis. Moreover, aberrant expression of an RBP in a disease state would have deleterious downstream effects on synaptic function. While many underlying mechanisms of synaptic dysfunction in Alzheimer's disease (AD) have been prop...

Apolipoprotein E (APOE) ε4 is a genetic risk factor for Alzheimer's disease (AD). Social support may confer protection against cognitive decline even in the presence of APOE ε4. We examined the relationship among APOE ε4 allele(s) carrier status, social support (overall and sub-sources), and cognition in 115 older adults (72.24 ± 8.29 years; 71.3%...

Introduction Growing interest centers on the association between circulating ketone bodies (KB) and cognitive function, notably in aging and neurodegenerative diseases. Methods Associations of plasma KB with incident dementia and cognitive performances were examined among Multi‐Ethnic Study of Atherosclerosis (MESA) participants. KB were measured...

INTRODUCTION Adverse psychosocial exposure is associated with increased pro‐inflammatory gene expression and reduced type‐1 interferon gene expression known as the conserved transcriptional response to adversity (CTRA). CTRA is not well‐studied in cognitive impairment but may contribute to late‐life cognitive decline. METHODS We examined perceived...

Objectives Among participants with Alzheimer's disease (AD) we estimated the minimal clinically important difference (MCID) in apathy symptom severity on three scales. Design Retrospective anchor- and distribution-based analyses of change in apathy symptom scores. Setting Apathy in Dementia Methylphenidate Trial (ADMET) and ADMET 2 randomized con...

Background Intranasal insulin (INI) is being explored as a treatment for Alzheimer’s disease (AD). Improved memory, functional ability, and cerebrospinal fluid (CSF) AD biomarker profiles have been observed following INI administration. However, the method of intranasal delivery may significantly affect outcomes. Objective To show reliable deliver...

Importance Alzheimer’s disease (AD) is the most common cause of dementia in the elderly with the incidence rising exponentially after the age of 65 years. Unfortunately, effective treatments are extremely limited and definite diagnosis can only be made at autopsy. This is in part due to our limited understanding of the complex pathophysiology, incl...

INTRODUCTION Microtubule (MT) stability is crucial for proper neuronal function. Understanding MT dysregulation is critical for connecting amyloid beta (Aβ) and tau‐based degenerative events and early changes in presymptomatic Alzheimer's disease (AD). Herein we present positron emission tomography (PET) imaging properties of our MT‐PET radiotracer...

Alzheimer’s disease (AD) is influenced by a variety of modifiable risk factors, including a person’s dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD’s metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study in...

Objectives To examine clinically important adverse events (AEs) associated with methylphenidate (MPH) treatment of apathy in Alzheimer's Disease (AD) versus placebo, including weight loss, vital signs, falls, and insomnia. Methods The Apathy in Dementia Methylphenidate Trial 2 (ADMET2) trial was a multicenter randomized, placebo‐controlled trial o...

INTRODUCTION We evaluated associations between plasma and neuroimaging‐derived biomarkers of Alzheimer's disease and related dementias and the impact of health‐related comorbidities. METHODS We examined plasma biomarkers (neurofilament light chain, glial fibrillary acidic protein, amyloid beta [Aβ] 42/40, phosphorylated tau 181) and neuroimaging m...

Alzheimer's Disease (AD) is the most common cause of dementia, although multiple pathologies are found in nearly half of the cases with clinically diagnosed AD. Prion diseases, such as Creutzfeldt-Jakob disease (CJD), are rare causes of dementia and typically manifest as a rapidly progressive dementia, where symptom onset to dementia most often occ...

Background The preclinical Alzheimer’s cognitive composite (PACC) was developed for in-person administration to capture subtle cognitive decline. At the outset of the COVID-19 pandemic, cognitive testing was increasingly performed remotely by telephone or video administration. It is desirable to have a harmonized composite measurement derived from...

Blood based mitochondrial bioenergetic profiling is a feasible, economical, and minimally invasive approach that can be used to examine mitochondrial function and energy metabolism in human subjects. In this study, we use two complementary respirometric techniques to evaluate mitochondrial bioenergetics in both intact and permeabilized peripheral b...

Senescent cell accumulation contributes to the progression of age-related disorders including Alzheimer’s disease (AD). Clinical trials evaluating senolytics, drugs that clear senescent cells, are underway, but lack standardized outcome measures. Our team recently published data from the first open-label trial to evaluate senolytics (dasatinib plus...

Retinal vessel calibers share anatomic and physiologic characteristics with the cerebral vasculature and can be visualized noninvasively. In light of the known microvascular contributions to brain health and cognitive function, we aimed to determine if, in a community based-study, retinal vessel calibers and change in caliber over 8 years are assoc...

Background Frontotemporal dementia (FTD) represents a collection of neurobehavioral and neurocognitive syndromes that are associated with a significant degree of clinical, pathological, and genetic heterogeneity. Such heterogeneity hinders the identification of effective biomarkers, preventing effective targeted recruitment of participants in clini...

Background:Apathy is the most common neuropsychiatric symptom in Alzheimer’s disease (AD), however there are no approved treatments. In the recent Apathy in Dementia Methylphenidate Trial 2 (ADMET 2), methylphenidate treatment resulted in a significant reduction in apathy with a small to medium effect size. We assessed response in ADMET 2 to identi...

Background Sleep disturbances in dementia occur often, are reported as neuropsychiatric symptoms, and are associated with higher caregiver burden and institutionalization. In mild cognitive impairment (MCI), sleep changes co‐occur with increasing neuropsychiatric symptoms and cognitive decline. Diet quality, like sleep, is a modifiable risk factor...

Background Recent studies identified the lymphatic drainage system in the brain. Here, cerebrospinal fluid (CSF) carries waste from brain tissue. However, it is still not well understood how CSF flow in the brain affects waste removal. In this study, we hypothesize that CSF flow patterns in the subarachnoid space will be correlated with beta‐amyloi...

Background AD Imaging biomarkers (IBM) include measures of amyloid (A) on PET, and neurodegeneration (N) on MRI, with thresholds for classification of imaging A/N positivity commonly used at research centers. Novel AD plasma biomarkers (PBM) can potentially enhance neuropathological characterization; however, knowledge regarding which thresholds to...

Background Subclinical cardiovascular disease (CVD) measures may reflect biological pathways that contribute to increased risk for CVD events and dementia beyond conventional risk scores. Therefore, we examined whether subclinical CVD biomarkers: 1) dissociate into composites representing distinct pathologic pathways that 2) predict future risk of...

Background Mixed model repeated measures (MMRM) is the most common analysis approach in clinical trials for Alzheimer’s disease. The model treats time as a categorical variable, which can be problematic when assessments occur off‐schedule, as including off‐schedule visits can induce bias, and excluding them ignores valuable information and violates...

Background Impaired glucose utilization is central to the pathogenesis of Alzheimer’s disease. In a hypometabolic state, the brain depends on alternative sources of energy, including amino acids, fatty acids, and ketone bodies (KBs). As KBs can cross the blood‐brain barrier, it is considered that a ketogenic diet could augment the high energetic de...

Background As blood‐based biomarkers of Alzheimer’s disease enter clinical diagnostic use, key considerations remain including the concordance with CSF or amyloid PET and the comparability of results between different assay platforms. Method Participants (n = 42) from the Clinical Core of the Wake Forest ADRC, were selected using CSF Aβ42/Aβ40 val...

Background ADRD clinical trials often target preclinical disease, where hope of averting the pathologic cascade and eventual cognitive decline remains highest. The preclinical Alzheimer’s cognitive composite (PACC5) was developed for in‐person administration to capture subtle cognitive decline. Early cognitive fluctuations may inform multidirection...

Background Frontotemporal dementia (FTD) represents a collection of neurocognitive syndromes with frontotemporal lobar degeneration (FTLD) neuropathology, and is associated with significant clinical, pathological, and genetic heterogeneity. We trained a deep neural network (DNN) classifier to differentiate behavioral‐variant FTD (bvFTD), semantic v...

Background Brain vascular health is closely related to cognitive performance, and cerebrovascular reactivity (CVR), an indicator of cerebral blood flow (CBF) compensatory capacity in response to vasoactive stimuli, may help elucidate this relationship. Arterial spin labeling (ASL) and blood‐oxygen‐level‐dependent (BOLD) are two representative metho...

Background Elevated blood pressure levels during mid‐life have been found to be associated with an increased susceptibility to developing dementia later in life, particularly vascular dementia. Quantitative imaging biomarkers, such as Oxygen Extraction Fraction (OEF) and Cerebral Metabolism Rate of Oxygen (CMRO2), can be indicators of impaired cere...

Background Hypertension is one of the key vascular risk factors of AD and related dementia. Cerebral blood flow (CBF) and white matter (WM) integrity may play an essential role in understanding the vascular contributions to dementia (VCID). We investigated if hypertension is related to WM microstructural and vascular imaging metrics in WM. Method...

Background Western vs. Mediterranean patterned diets have been associated with divergent effects on neurodegenerative diseases including Alzheimer’s Disease (AD). Such effects may be mediated through the gut microbiome, although the exact mechanisms linking diet, microbiome, and brain outcomes remain unclear. Oscillospira, a genus of gut‐dwelling b...

Background Prior studies have demonstrated that shape analysis of the hippocampus may provide a more accurate prognostic prediction of cognitive decline than simply volume. Here we deploy a novel automated pipeline for hippocampal morphometry to elucidate the surface regions sensitive to shape change along the AD spectrum. Methods Hippocampal volu...

Background Alzheimer’s Disease (AD) is a progressive cognitive disorder where synapse loss has been well documented. Identifying and restoring molecular targets that are involved in synapse loss is crucial in restoring balanced synaptic function and communication. FMRP is an RNA‐binding protein that is essential protein for synapse formation and st...

Background Otherwise cognitively normal individuals can experience age‐related cognitive dysfunction and may present with heterogenous patterns of cognitive impairment. There is limited knowledge regarding the presence and stability of cognitive subtypes observed in individuals with mild cognitive impairment and dementia (e.g., dysexecutive, non‐am...

Background Prior studies have demonstrated the safety of amyloid PET scan disclosure to research participants. However, existing research has been conducted in predominantly white, cognitively intact, and highly educated samples. The Wake Forest Alzheimer’s Disease Research Center (ADRC) implemented a protocol to provide amyloid PET disclosure to a...

Background Knowledge regarding associations between plasma and neuroimaging biomarkers indexing neurodegeneration and neuropathology observed in dementia is limited. Further, it is uncertain how comorbid health complications (e.g., kidney function) may alter plasma levels and impact associations with neuroimaging biomarkers. Method We examined ass...

Background Alzheimer’s Disease (AD) is a progressive neurocognitive disorder with irreversible hippocampal atrophy and degradation of cognitive function. Hippocampal atrophy can be assessed by volume and shape changes on MRI, and hippocampal volume is a sensitive marker for AD diagnosis and progression; however, it does not reflect regional changes...

Background There is an increasing interest in using machine learning and artificial intelligence to estimate chronological age using neuroimaging data. The gap between chronological age and estimated brain age (brain age gap, BAG) is used as a measure of accelerated/resilient brain aging. Previously, BAG has been associated with cognitive status. H...

Background Social determinants of health (SDoH) are important environmental factors in cardiometabolic risk and cognitive aging. Area Deprivation Index (ADI) is a measure of neighborhood‐level socioeconomic disadvantage and has been studied in normal cognition (NC), but relatively less is known about impact in those with mild cognitive impairment (...

Background In humans, social integration wanes with age, a pattern hypothesized to stem from cognitive or physical decrements. Social isolation increases dementia risk. Nonhuman primates provide important translational opportunities to study brain‐body relationships that may promote healthy or pathological aging. Vervet monkeys ( Chlorocebus sabaeu...

Background The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) found that methylphenidate (MPH) was modestly efficacious is treating apathy in Alzheimer’s disease (AD) with 66% response (> = 4 point decrease on Neuropsychiatric Inventory – apathy (NPI‐A). Here, we evaluated if blood‐based biomarkers potentially associated with treatment‐limiti...

Background Mediterranean diets may reduce Alzheimer’s disease (AD) risk and preserve cognitive function relative to Western diets in part by protecting against neuroinflammation. In middle‐aged humans that subsequently develop AD, increased cortical thickness precedes atrophy. It is hypothesized that the initial increase in brain volumes may be due...

Background While microtubule (MT)‐destabilization and synaptic loss hallmark AD pathological events, no study has systematically quantified their in vivo levels in the same brain. Any therapeutic intervention relying on MT destabilization and synaptic vesicle protein (SV2A) levels will benefit from a dual PET imaging strategy, providing target enga...

Background The Uniform Data Set Neuropsychological Battery, Version 3 (UDSv3) was designed for face‐to‐face assessment of cognition within Alzheimer’s Disease Research Centers (ADRCs) in the USA. However, there are many reasons research participants may be unable to meet face‐to‐face for assessments. This inter‐ADRC, multi‐site study will validate...

Background Frontotemporal dementia (FTD) represents a collection of neurocognitive syndromes with frontotemporal lobar degeneration (FTLD) neuropathology, and is associated with significant clinical, pathological, and genetic heterogeneity. We trained a deep neural network (DNN) classifier to differentiate behavioral‐variant FTD (bvFTD), semantic v...

Background Knowledge regarding associations between plasma and neuroimaging biomarkers indexing neurodegeneration and neuropathology observed in dementia is limited. Further, it is uncertain how comorbid health complications (e.g., kidney function) may alter plasma levels and impact associations with neuroimaging biomarkers. Method We examined ass...

Background ADRD clinical trials often target preclinical disease, where hope of averting the pathologic cascade and eventual cognitive decline remains highest. The preclinical Alzheimer’s cognitive composite (PACC5) was developed for in‐person administration to capture subtle cognitive decline. Early cognitive fluctuations may inform multidirection...

Background Mediterranean diets may reduce Alzheimer’s disease (AD) risk and preserve cognitive function relative to Western diets in part by protecting against neuroinflammation. In middle‐aged humans that subsequently develop AD, increased cortical thickness precedes atrophy. It is hypothesized that the initial increase in brain volumes may be due...

Background While microtubule (MT)‐destabilization and synaptic loss hallmark AD pathological events, no study has systematically quantified their in vivo levels in the same brain. Any therapeutic intervention relying on MT destabilization and synaptic vesicle protein (SV2A) levels will benefit from a dual PET imaging strategy, providing target enga...

Background AD Imaging biomarkers (IBM) include measures of amyloid (A) on PET, and neurodegeneration (N) on MRI, with thresholds for classification of imaging A/N positivity commonly used at research centers. Novel AD plasma biomarkers (PBM) can potentially enhance neuropathological characterization; however, knowledge regarding which thresholds to...

Background Hypertension is one of the key vascular risk factors of AD and related dementia. Cerebral blood flow (CBF) and white matter (WM) integrity may play an essential role in understanding the vascular contributions to dementia (VCID). We investigated if hypertension is related to WM microstructural and vascular imaging metrics in WM. Method...

Objective Face-to-face administration is the “gold standard” for both research and clinical cognitive assessments. However, many factors may impede or prevent face-to-face assessments, including distance to clinic, limited mobility, eyesight, or transportation. The COVID19 pandemic further widened gaps in access to care and clinical research partic...

Objective There is a pressing need for sensitive, non-invasive indicators of cognitive impairment in those at risk for Alzheimer’s disease (AD). One group at an increased risk for AD is APOEε4 carriers. One study found that cognitively normal APOEε4 carriers are less likely to produce low frequency (i.e., less common) words on semantic fluency task...

Alzheimer's disease (AD) is influenced by a variety of modifiable risk factors, including a person's dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD's metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study in...