Cerebral Amyloid Angiopathy, Dementia, and Alzheimer Neuropathologic Changes: Findings From the ACT Autopsy Cohort.

Background And Objectives: Cerebral amyloid angiopathy (CAA) is common in older adults and is associated with dementia. Less is known whether this association is mediated by Alzheimer disease (AD) neuropathologic changes, the examination of which was the objective of this study.

Methods: This was a retrospective cross-sectional examination of the Kaiser Permanente Washington database of the Adult Changes in Thought (ACT) autopsy cohort with information on CAA, dementia, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) (amyloid neuritic plaques), and Braak (tau neurofibrillary tangles).

Late-Life Blood Pressure and Cerebral Amyloid Angiopathy: Findings from the U.S. National Alzheimer's Coordinating Center Uniform Dataset.

High blood pressure (BP) and cerebral amyloid angiopathy (CAA) are two common risk factors for intracranial hemorrhage, potentially leading to cognitive impairment. Less is known about the relationship between BP and CAA, the examination of which was the objective of this study. We analyzed data from 2510 participants in the National Alzheimer's Coordinating Center (NACC) who had information on longitudinal BP measurements before death and on CAA from autopsy.

Stroke Incidence in Patients With Hypertension According to Cardiorespiratory Fitness.

Background: Hypertension and physical inactivity are risk factors for stroke. The effect of cardiorespiratory fitness (CRF) on stroke risk in patients with hypertension has not been assessed. We evaluated stroke incidence in patients with hypertension according to CRF and changes in CRF.

A Novel Explainable AI Method to Assess Associations between Temporal Patterns in Patient Trajectories and Adverse Outcome Risks: Analyzing Fitness as a Risk Factor of ADRD.

We present a novel explainable artificial intelligence (XAI) method to assess the associations between the temporal patterns in the patient trajectories recorded in longitudinal clinical data and the adverse outcome risks, through explanations for a type of deep neural network model called Hybrid Value-Aware Transformer (HVAT) model. The HVAT models can learn jointly from longitudinal and non-longitudinal clinical data, and in particular can leverage the time-varying numerical values associated with the clinical codes or concepts within the longitudinal data for outcome prediction. The key component of the XAI method is the definitions of two derived variables, the temporal mean and the temporal slope, which are defined for the clinical concepts with associated time-varying numerical values.

Relationship between Cerebral Microinfarcts and Dementia by Sex: Findings from a community-based Autopsy Study.

Cerebral microinfarcts are common in older adults and are associated with cognitive impairment. Less is known about sex-related variation in the relationship between cerebral microinfarcts and dementia in older adults, the examination of which was the objective of this study. This case-control study was based on the 727 participants (419 women) in the Adult Changes in Thought (ACT) autopsy data.

Anti-Amyloid Therapy, AD, and ARIA: Untangling the Role of CAA.

Anti-amyloid therapies (AATs), such as anti-amyloid monoclonal antibodies, are emerging treatments for people with early Alzheimer's disease (AD). AATs target amyloid β plaques in the brain. Amyloid-related imaging abnormalities (ARIA), abnormal signals seen on magnetic resonance imaging (MRI) of the brain in patients with AD, may occur spontaneously but occur more frequently as side effects of AATs.

Relationships between Late-Life Blood Pressure and Cerebral Microinfarcts in Octogenarians: An Observational Autopsy Study.

Mid-life high blood pressure (BP) is a risk factor for cerebral microinfarcts. Less is known about the relationship between late-life BP and cerebral microinfarcts, the examination of which is the objective of the current study. This case-control study analyzed data from 551 participants (94.

Hybrid Value-Aware Transformer Architecture for Joint Learning from Longitudinal and Non-Longitudinal Clinical Data.

Transformer is the latest deep neural network (DNN) architecture for sequence data learning, which has revolutionized the field of natural language processing. This success has motivated researchers to explore its application in the healthcare domain. Despite the similarities between longitudinal clinical data and natural language data, clinical data presents unique complexities that make adapting Transformer to this domain challenging.

Relationships between Cerebral Vasculopathies and Microinfarcts in a Community-Based Cohort of Older Adults.

Cerebral microinfarcts are associated with cognitive impairment and dementia. Small vessel diseases such as cerebral arteriolosclerosis and cerebral amyloid angiography (CAA) have been found to be associated with microinfarcts. Less is known about the associations of these vasculopathies with the presence, numbers, and location of microinfarcts.

Characteristics and Predictors of Alzheimer's Disease Resilience Phenotype.

Alzheimer's disease (AD) is characterized by cognitive impairment in the presence of cerebral amyloid plaques and neurofibrillary tangles. Less is known about the characteristics and predictors of resilience to cognitive impairment in the presence of neuropathological evidence of AD, the focus of this study. Of 3170 adults age ≥65 years in the National Alzheimer's Coordinating Center (NACC) brain autopsy cohort, 1373 had evidence of CERAD level moderate to frequent neuritic plaque density and Braak stage V-VI neurofibrillary tangles.

Hybrid Value-Aware Transformer Architecture for Joint Learning from Longitudinal and Non-Longitudinal Clinical Data.

Transformer is the latest deep neural network (DNN) architecture for sequence data learning that has revolutionized the field of natural language processing. This success has motivated researchers to explore its application in the healthcare domain. Despite the similarities between longitudinal clinical data and natural language data, clinical data presents unique complexities that make adapting Transformer to this domain challenging.

Enhancing Clinical Data Analysis by Explaining Interaction Effects between Covariates in Deep Neural Network Models.

Deep neural network (DNN) is a powerful technology that is being utilized by a growing number and range of research projects, including disease risk prediction models. One of the key strengths of DNN is its ability to model non-linear relationships, which include covariate interactions. We developed a novel method called interaction scores for measuring the covariate interactions captured by DNN models.

Medication-Wide Association Study Plus (MWAS+): A Proof of Concept Study on Drug Repurposing.

The high cost and time for developing a new drug or repositioning a partially-developed drug has fueled interest in "repurposing" drugs. Drug repurposing is particularly of interest for Alzheimer's disease (AD) or AD-related dementias (ADRD) because there are no unrestricted disease-modifying treatments for ADRD. We have designed and pilot tested a 3-Step Medication-Wide Association Study Plus (MWAS+) approach to rigorously accelerate the identification of drugs with a high potential to be repurposed for delaying and preventing AD/ADRD: Step 1 is a hypothesis-free exploration; Step 2 is mechanistic filtering; And Step 3 is hypothesis testing using observational data and prospective cohort design.

Severe hyposmia distinguishes neuropathologically confirmed dementia with Lewy bodies from Alzheimer's disease dementia.

Many subjects with neuropathologically-confirmed dementia with Lewy bodies (DLB) are never diagnosed during life, instead being categorized as Alzheimer's disease dementia (ADD) or unspecified dementia. Unrecognized DLB therefore is a critical impediment to clinical studies and treatment trials of both ADD and DLB. There are studies that suggest that olfactory function tests may be able to distinguish DLB from ADD, but few of these had neuropathological confirmation of diagnosis.

Can motor function uncertainty and local instability within upper-extremity dual-tasking predict amnestic mild cognitive impairment and early-stage Alzheimer's disease?

In this study, we examined the uncertainty and local instability of motor function for cognitive impairment screening using a previously validated upper-extremity function (UEF). This approach was established based upon the fact that elders with an impaired executive function have trouble in the simultaneous execution of a motor and a cognitive task (dual-tasking). Older adults aged 65 years and older were recruited and stratified into 1) cognitive normal (CN), 2) amnestic MCI of the Alzheimer's type (aMCI), and 3) early-stage Alzheimer's Disease (AD).

Correlation Between the Movement Disorder Society's Unified Parkinson's Disease Rating Scale and Nonmotor Scales in Patients with Parkinson's Disease.

The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDSUPDRS), Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), Mayo Sleep Questionnaire, Epworth Sleepiness Scale, and Neuropsychiatric Inventory Questionnaire (NPI-Q) are validated instruments for assessing signs and symptoms of Parkinson's disease (PD). We sought to determine whether responses on the MDS-UPDRS correlate with responses to other scales used in patients with PD. Study subjects were enrolled in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND).

Cardiac sympathetic denervation and synucleinopathy in Alzheimer's disease with brain Lewy body disease.

Comorbid Lewy body pathology is very common in Alzheimer's disease and may confound clinical trial design, yet there is no test to identify patients with this. Tissue (and/or radioligand imaging) studies have shown cardiac sympathetic denervation in Parkinson's disease and dementia with Lewy bodies, but this has not been explored in Alzheimer's subjects with Lewy bodies not meeting dementia with Lewy bodies clinicopathological criteria. To determine if Alzheimer's disease with Lewy bodies subjects show sympathetic cardiac denervation, we analysed epicardial and myocardial tissue from autopsy-confirmed cases using tyrosine hydroxylase and neurofilament immunostaining.

Do Parkinson disease subject and caregiver-reported Epworth sleepiness scale reponses correlate?

Objective: Subjective excessive daytime sleepiness, commonly measured with the Epworth Sleepiness Scale (ESS), is associated with cognitive impairment in Parkinson disease (PD). Significant correlation between subject and informant responses has been reported in neurologically healthy individuals. We sought to assess this correlation in patients with PD.

Neuropathological Findings in Parkinson's Disease With Mild Cognitive Impairment.

Objective: There are few neuropathological studies on Parkinson's disease with mild cognitive impairment (PD-MCI). Those published reveal coexisting Lewy body and Alzheimer's disease pathology. Our objective is to determine the pathology that underlies PD-MCI.

Unified Staging System for Lewy Body Disorders: Clinicopathologic Correlations and Comparison to Braak Staging.

This study was designed to correlate clinical findings with the extent of pathologic a-synuclein (aSyn) in the brain using the Unified Staging System for Lewy Body disorders (USSLB). Data from 280 cases from the Arizona Study of Aging and Neurodegenerative Disorders are presented. Each case had a complete USSLB staging and at least 1 full research clinical assessment, including subspecialty neurologist-administered movement and cognitive evaluation.

Screening older adults for amnestic mild cognitive impairment and early-stage Alzheimer's disease using upper-extremity dual-tasking.

The purpose of the current study was to develop an objective tool based on dual-task performance for screening early-stage Alzheimer's disease (AD) and mild cognitive impairment (MCI of the Alzheimer's type). Dual-task involved a simultaneous execution of a sensor-based upper-extremity function (UEF) motor task (normal or rapid speed) and a cognitive task of counting numbers backward (by ones or threes). Motor function speed and variability were recorded and compared between cognitive groups using ANOVAs, adjusted for age, gender, and body mass index.

Brain Lewy-Type Synucleinopathy Density Is Associated with a Lower Prevalence of Atherosclerotic Cardiovascular Disease Risk Factors in Patients with Parkinson's Disease1.

Background: Some epidemiology studies suggest that atherosclerotic cardiovascular disease (ASCVD) risk factors increase the risk of developing Parkinson's disease (PD). However, conflicting data suggest lower rates of ASCVD in PD.

Objective: The objective of this study is to determine, with data from a longitudinal clinicopathological study, whether ASCVD risk factors are associated with a PD diagnosis and/or increased brain or peripheral load of Lewy-type synucleinopathy (LTS).

Faster cognitive decline in dementia due to Alzheimer disease with clinically undiagnosed Lewy body disease.

Background: Neuropathology has demonstrated a high rate of comorbid pathology in dementia due to Alzheimer's disease (ADD). The most common major comorbidity is Lewy body disease (LBD), either as dementia with Lewy bodies (AD-DLB) or Alzheimer's disease with Lewy bodies (AD-LB), the latter representing subjects with ADD and LBD not meeting neuropathological distribution and density thresholds for DLB. Although it has been established that ADD subjects with undifferentiated LBD have a more rapid cognitive decline than those with ADD alone, it is still unknown whether AD-LB subjects, who represent the majority of LBD and approximately one-third of all those with ADD, have a different clinical course.