Erika Driver-Dunckley's research while affiliated with Mayo Clinic - Scottsdale and other places
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Publications (82)
Introduction:
We examined the progression of extrapyramidal symptoms and signs in autopsy-confirmed dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and Alzheimer's disease dementia (AD).
Methods:
Longitudinal data were obtained from Arizona Study of Aging and Neurodegenerative Disease, with PDD (n = 98), AD (n = 47) and DLB...
Background:
Essential tremor (ET) is a common movement disorder in which cerebellar microscopic and volume alterations have been repeatedly reported although with disagreement between studies. However, pronounced heterogeneity was found with regard to cerebellar volume alterations.
Objective:
This study aimed to assess postmortem cerebellar volu...
We previously reported that in our autopsy‐confirmed cohort of Dementia with Lewy Bodies (DLB), Parkinson’s Disease Dementia (PDD) and Alzheimer’s Disease (AD), DLB with parkinsonism (DLB+Park) predicted faster progression of UPDRS‐III scores compared to PDD, DLB without parkinsonism (DLB‐Park), and AD. This study examined annualized rate of change...
OBJECTIVE
Assess clinical and pathological correlations of jaw tremor in three cohorts enrolled in a longterm aging study.
BACKGROUND
Jaw/lip tremor has been described in various movement disorders but the impact of seeing a jaw tremor on clinician diagnosis and whether the presence of isolated jaw tremor is correlated with subsequent phenoconvers...
Brains of 42 COVID-19 decedents and 107 non-COVID-19 controls were studied. RT-PCR screening of 16 regions from 20 COVID-19 autopsies found SARS-CoV-2 E gene viral sequences in 7 regions (2.5% of 320 samples), concentrated in 4/20 subjects (20%). Additional screening of olfactory bulb (OB), amygdala (AMY) and entorhinal area for E, N1, N2, RNA-depe...
The Alzheimer disease (AD) neuropathological hallmarks amyloid β (Aβ) and tau neurofibrillary (NF) pathology have been reported in the olfactory bulb (OB) in aging and in different neurodegenerative diseases, which coincides with frequently reported olfactory dysfunction in these conditions. To better understand when the OB is affected in relation...
Decline of olfactory function is frequently observed in aging and is an early symptom of neurodegenerative diseases. As the olfactory bulb (OB) is one of the first regions involved by pathology and may represent an early disease stage, we specifically aimed to evaluate the contribution of OB pathology to olfactory decline in cognitively normal aged...
Objective:
The Uniform Data Set 3.0 neuropsychological battery (UDS3NB) is well developed for research with Alzheimer's disease and related dementias, and may serve as a common set of measures of cognitive decline across neurodegenerative diseases. However, the battery has not been formally assessed in persons with Parkinson's disease (PD). The cu...
Background
Although parkinsonism is a core feature of Parkinson’s Disease Dementia (PDD) and Dementia with Lewy bodies (DLB), its evolution is less delineated. We aimed to assess differences in severity and progression of parkinsonian motor symptoms and signs in a community autopsy cohort with clinicopathologic diagnosis of DLB, PDD or Alzheimer’s...
Background:
Braak and others have proposed that Lewy-type α-synucleinopathy in Parkinson's disease (PD) may arise from an exogenous pathogen that passes across the gastric mucosa and then is retrogradely transported up the vagus nerve to the medulla.
Objective:
We tested this hypothesis by immunohistochemically staining, with a method specific f...
Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease. It is presently only accurately diagnosed at an advanced stage by a series of motor deficits, which are predated by a litany of non-motor symptoms manifesting over years or decades. Aberrant epigenetic modifications exist across a range of diseases and are non...
Background:
Imaging biomarkers have the potential to distinguish between different brain pathologies based on the type of ligand used with PET. AV-45 PET (florbetapir, Amyvid) is selective for the neuritic plaque amyloid of Alzheimer's disease (AD), while AV-133 PET (florbenazine) is selective for VMAT2, which is a dopaminergic marker.
Objective:...
Background
Progressive supranuclear palsy is a neurodegenerative disorder associated with tau protein aggregation. Tilavonemab (ABBV-8E12) is a monoclonal antibody that binds to the N-terminus of human tau. We assessed the safety and efficacy of tilavonemab for the treatment of progressive supranuclear palsy.
Methods
We did a phase 2, multicentre,...
Background:
Hyposmia is characteristic of idiopathic Parkinson's disease (PD) and dementia with Lewy bodies (DLBs), whereas progressive supranuclear palsy (PSP) typically has normal sense of smell. However, there is a lack of pathologically confirmed data.
Objective:
The objective is to study hyposmia in pathologically confirmed PSP patients and...
The coronavirus SARS-CoV-2 (SCV2) causes acute respiratory distress, termed COVID-19 disease, with substantial morbidity and mortality. As SCV2 is related to previously-studied coronaviruses that have been shown to have the capability for brain invasion, it seems likely that SCV2 may be able to do so as well. To date, although there have been many...
There has been a markedly renewed interest in factors associated with pneumonia, a leading cause of death worldwide, due to its frequent concurrence with pandemics of influenza and Covid-19 disease. Reported predisposing factors to both bacterial pneumonia and pandemic viral lower respiratory infections are wintertime occurrence, older age, obesity...
Objectives
Update data for diagnostic accuracy of a clinical diagnosis of Parkinson’s disease (PD) using neuropathological diagnosis as the gold standard.
Methods
Data from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) was used to determine the predictive value of a clinical PD diagnosis. Two clinical diagnostic confidence le...
Braak and others have proposed that Lewy-type α-synucleinopathy (aSyn) in Parkinson’s disease (PD) may arise from an exogenous pathogen that passes across the gastric mucosa and then is retrogradely transported up the vagus nerve to the medulla. We tested this “body-first” hypothesis by immunohistochemically staining stomach and vagus nerve tissue...
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 th...
Background
Mobility in Parkinson’s disease (PD) is restricted due to impairments in gait and postural control. Although typical dance-based movement programs are beneficial in PD, many did not improve gait which may be due to the nature of the training, limited data, or both. Moreover, the investigation of the effects of a dance program specificall...
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.
Methods:
We used data from the Arizona Study of Aging and Neurodegenerative Disorders,...
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 w...
Comorbid Lewy body pathology is very common in Alzheimer’s disease and may confound clinical trial design, yet there is no in vivo 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 Alzheim...
Common motor impairments in Parkinson’s disease (PD) include reduced step length, shuffling gait, and postural instability; these can be aggravated by the presence of stooped posture. The severity of these impairments worsen over time and affect quality of life. Neurorehabilitation therapies may help to sustain, or possibly improve, motor function...
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...
Background:
Abnormal color vision and contrast acuity may have significant impact on daily activities.
Objective:
Evaluate color visual acuity, at high and low contrast, in Parkinson's disease (PD) and controls using an iPad application.
Methods:
Color visual acuity was tested with the Variable Contrast Acuity Chart (King-Devick Test LLC, Oakb...
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 neuropa...
Background:
Verbal fluency deficits are common in patients with Parkinson's disease. The association of these impairments with regional neuropathological changes is unexplored.
Objectives:
Determine if patients with verbal fluency impairments have greater neuropathological burden in frontal, temporal, and limbic regions and if Lewy bodies or neu...
Neuropathology has demonstrated a high rate of comorbid pathology in dementia due to Alzheimer disease (ADD). The most common major comorbidity is Lewy body disease (LBD), either as dementia with Lewy bodies (AD-DLB) or Alzheimer disease with Lewy bodies (AD-LB), the latter representing subjects with ADD and LBD not meeting neuropathological distri...
Objective
Identify clinical features predictive of Lewy body pathology in AD patients in an ongoing longitudinal clinicopathologic study.
Material & Methods
We queried the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) database for dementia cases with AD pathology (1997‐2015). Subjects received longitudinal comprehensive clinical...
Background and objective:
Weight loss and small intestinal bacterial overgrowth (SIBO) are common in Parkinson's disease (PD). We aimed to study the relationship between weight loss and SIBO in PD.
Methods:
This was a cross-sectional study with a prospective, interventional component. Consecutive patients seen in the PD clinic who agreed to part...
Inability to accurately diagnose Lewy type alpha-synucleinopathy (LTS) pre-mortem has been a major obstacle to clinical care and research. Probable REM sleep behavior disorder (PRBD) diagnosed with support of instruments such as the Mayo Sleep Questionnaire (MSQ) may provide a cost effective means of predicting LTS. Since 2007, 602 subjects in the...
Background
Clinical diagnostic criteria for PD rely on rest tremor, bradykinesia, and rigidity. These features are non‐specific and neuropathological confirmation remains the gold standard for diagnosis. This study presents data on clinical certainty ratings in autopsy‐proven PD.
Methods
Subjects were assessed annually by a movement disorders spec...
Objective
To assess the predictive potential of the complete response pattern from the University of Pennsylvania Smell Identification Test for the diagnosis of Parkinson's disease.
Methods
We analyzed a large dataset from the Arizona Study of Aging and Neurodegenerative Disorders, a longitudinal clinicopathological study of health and disease in...
Introduction:
Depression and neuropsychiatric disorders in individuals with essential tremor (ET) are not well characterized in the literature.
Methods:
We compared 104 ET subjects with 481 non-ET controls involved in the Arizona Study of Aging and Neurodegenerative Disorders. An analysis of baseline depression scales and neuropsychiatric invent...
Background:
The aim of this postmortem study was to compare, in Parkinson's disease subjects with and without bilateral subthalamic nucleus deep brain stimulation (STN-DBS), the loss of pigmented neurons within the substantia nigra and pathological alpha-synuclein density within the SN and other brain regions.
Methods:
PD subjects were identifie...
Multiple studies suggest that females are affected by Alzheimer disease (AD) more severely and more frequently than males. Other studies have failed to confirm this and the issue remains controversial. Difficulties include differences in study methods and male versus female life expectancy. Another element of uncertainty is that the majority of stu...
Objective:
We sought to determine the underlying cortical gene expression changes associated with Parkinson dementia using a next-generation RNA sequencing approach.
Methods:
In this study, we used RNA sequencing to evaluate differential gene expression and alternative splicing in the posterior cingulate cortex from neurologically normal control...
Objective:
To identify a panel of peripheral inflammatory/immune mediators that could discriminate Parkinson disease with dementia (PDD) from Parkinson disease (PD) without dementia.
Methods:
Plasma samples from 52 patients with PD and 22 patients with PDD were prepared from freshly collected blood following an institutional review board-approve...
Introduction:
Finding a peripheral tissue biopsy site to diagnose early PD would be of value for clinical care, biomarker validation, and as research enrollment criteria. Whereas autopsy and advanced PD studies suggest that the submandibular gland is an important biopsy site, there are no studies in early PD. The aim of this study was to determine...
Background:
Clinical misdiagnosis, particularly at early disease stages, is a roadblock to finding new therapies for Lewy body disorders. Biopsy of a peripheral site might provide improved diagnostic accuracy. Previously, we reported, from both autopsy and needle biopsy, a high prevalence of submandibular gland synucleinopathy in Parkinson's disea...
Although there are studies investigating the pathologic origins of mild cognitive impairment (MCI), they have revolved around comparisons to normal elderly individuals or those with Alzheimer's disease (AD) or other dementias. There are few studies directly comparing the comprehensive neuropathology of amnestic (aMCI) and nonamnestic (naMCI) MCI.
T...
Background:
We evaluated a simplified method for converting Unified Parkinson's Disease Rating Scale Part III Motor Examination total scores (UPDRS III) to the International Parkinson and Movement Disorder Society's (MDS) revised version of the scores.
Methods:
PD patients in the Arizona Study of Aging and Neurodegenerative Disorders were assess...
IntroductionRapid eye movement (REM) sleep behavior disorder (RBD) in Parkinson's disease (PD) is associated with differences in clinical phenotype, including dementia, autonomic loss, and gait dysfunction. The pathological basis for this remains unclear.Methods
Parkinson's disease subjects in a longitudinal clinicopathologic study were screened fo...
Background
Hyposmia is common in Parkinson's disease (PD) and is also observed with normal aging. It can be ascertained through objective testing, but it is unclear whether patients are aware of deficits and whether this has implications for cognitive status.Methods
Subjects in the Arizona Study of Aging and Neurodegenerative Disorders were studied...
The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain-only donations and currently has banked more than 1600 brains. More than 430 whole-body donations have been received since this service was commenced in 2005. The collective academic output of th...
The pathologic changes of Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP) have been reported to coexist, but whether PSP pathology modifies the clinical course of those individuals is unknown. The aim of this study was to determine whether clinical features of pathologically confirmed PD subjects with concomitant PSP pathology dif...
Background:
Olfactory dysfunction in Parkinson's disease (PD) is well-established and may represent one of the earliest signs of the disease.
Objective & methods:
The objective of this study was to evaluate the relationship of olfactory dysfunction, using the University of Pennsylvania Smell Identification Test (UPSIT), to clinical and pathologi...
Objectives:
Determine diagnostic accuracy of a clinical diagnosis of Parkinson disease (PD) using neuropathologic diagnosis as the gold standard.
Methods:
Data from the Arizona Study of Aging and Neurodegenerative Disorders were used to determine the predictive value of a clinical PD diagnosis, using 2 clinical diagnostic confidence levels, Poss...
Introduction
Many clinicopathological studies do not specify the presence of other pathologies located within the brain, so disease heterogeneity may be under appreciated.
Objective
The purpose of this study was to determine the frequencies of concomitant pathologies among parkinsonian disorders.
Methods
Data from the Arizona Study of Aging and N...
The objective is to examine the risk of dementia in subjects with essential tremor (ET) involved in the Arizona Study of Aging and Neurodegenerative Disorders. All subjects were free of a neurodegenerative diagnosis at baseline and had annual motor, general neurological, and neuropsychological assessments. Subjects with ET were compared with contro...
There has been controversy as to whether there is an underlying neurodegenerative process of the cerebellum in essential tremor (ET). The aim of this study was to examine whether ET is associated with Purkinje cell (PC) loss. Prospectively categorized ET and control subjects who were longitudinally examined in the Arizona Study for Aging and Neurod...
Objective:
This study investigates salivary gland biopsies in living patients with Parkinson disease (PD).
Methods:
Patients with PD for ≥5 years underwent outpatient transcutaneous needle core biopsies (18-gauge or 16-gauge) of 1 submandibular gland. Minor salivary glands were removed via a small incision in the lower lip. Tissue was fixed in f...
Existing reports on the frequencies of neurodegenerative diseases are typically based on clinical diagnoses. We sought to determine these frequencies in a prospectively assessed, community-based autopsy series. Included subjects had normal cognitive and movement disorder assessments at study entry. Of the 119 cases meeting these criteria, 52% were...
Data regarding autonomic function in restless legs syndrome (RLS) are limited to heart rate and blood pressure changes in cases with periodic limb movements (PLMS).
We compared autonomic symptoms of 49 subjects with RLS vs 291 control subjects using the Scales for Outcome in Parkinson disease-Autonomic (SCOPA-AUT) questionnaire, consisting of 23 it...
Objective:
To compare autonomic function of subjects with Parkinson's disease (PD) and essential tremor (ET) relative to controls.
Background:
It has been reported that patients with PD have autonomic dysfunction while no literature exists regarding autonomic function in ET.
Methods:
Subjects with PD, ET, and controls had autonomic function me...
Both hypothyroidism and Hashimoto's thyroiditis (HT) can rarely be associated with cerebellar ataxia. Severe essential tremor (ET) as well as bilateral thalamic deep brain stimulation (DBS) may lead to subtle cerebellar signs.
We report a 74-year-old male with hypothyroidism and a 20-year history of ET who developed cerebellar ataxia after bilatera...
The influence of gender on psychogenic nonepileptic seizures (PNES) diagnosis was examined retrospectively in 439 subjects undergoing video-EEG (vEEG) for spell classification, of whom 142 women and 42 men had confirmed PNES. The epileptologist's predicted diagnosis was correct in 72% overall. Confirmed epilepsy was correctly predicted in 94% men a...
The ability to understand how Parkinson's disease neurodegeneration leads to cortical dysfunction will be critical for developing therapeutic advances in Parkinson's disease dementia. The overall purpose of this project was to study the small-amplitude cortical myoclonus in Parkinson's disease as an in vivo model of focal cortical dysfunction secon...
Psychogenic non-epileptic seizures (PNES) and psychogenic movement disorders (PMDs) are common in neurology practice, yet it is not established whether clinically relevant differences between these two groups exist.
In this retrospective chart review 172 patients were identified (PNES n = 116, PMD n = 56).
The whole group was characterized by femal...
Compare the frequency of REM sleep behavior disorder (RBD) and excessive daytime sleepiness (EDS) in Parkinson's disease (PD), restless legs syndrome (RLS), essential tremor (ET), and control subjects.
Subjects enrolled in a longitudinal clinicopathologic study, and when available an informant, completed the Mayo Sleep Questionnaire, which asks "Ha...
Olfactory dysfunction in Parkinson's disease (PD) is an association that has been well documented in the medical literature, although the underlying pathophysiologic mechanism has not been clearly elucidated. In the Sun Health Research Institute Brain and Body Donation Program, subjects were tested for olfactory function. Olfaction was impaired in...
Restless legs syndrome is a common disoder that may interrupt sleep and has been reported to produce daytime fatigue and/or mood changes. This study assessed whether patients with RLS have more cognitive dysfunction and depression than individuals of the same age and education who do not have RLS. The study showed that older individuals with mild R...
We present a retrospective review of cases of painful legs and moving toes (PLMT) syndrome. Out of 4,780 database patients with movement disorders diagnosed at Mayo Clinic Arizona from 1996 to 2006, we identified 14 cases of PLMT and its variants (6 men, 8 women). Ages ranged from 25 to 84 years (mean, 69 years). Movements were bilateral in 12 and...
Our purpose was to characterize a state of mild cognitive impairment (MCI) in Parkinson's disease (PD) (PD-MCI) that would be analogous to the MCI that is posited as a precursor of Alzheimer's disease (AD). We categorized 86 PD subjects in a brain bank population as either cognitively normal (PD-CogNL), PD-MCI using criteria that included a 1.5 sta...
We report on 6 advanced Parkinson's disease (PD) patients who underwent bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery whose restless legs syndrome (RLS) improved postoperatively. Despite a mean 56% decrease in their levodopa equivalents postoperatively, their RLS scores dropped by a mean of 84% (100% in three). Our findin...
Topiramate is a broad-spectrum anticonvulsant that is now widely used for adult and pediatric epilepsy. In a singular case, topiramate was recently reported to benefit vascular hemichorea-hemiballismus. The authors describe three cases of hemichorea-hemiballismus, one of vascular etiology and two of metabolic etiology, effectively treated with topi...
Citations
... However, it is also clear that patients with ET may develop features of parkinsonism without the concomitant presence of neuropathological features of PD. Rest tremor (jaw/hand) in ET is not associated with an increased risk of Lewy body (LB) pathology [105,106] . Bradykinesia can be seen in aging ET patients and is not always associated with LB pathology [107,108] . ...
Reference: Essential tremor and ageing
... CNS-related symptoms can be a result of direct infection of CNS-resident cells by SARS-CoV-2, secondary effects stemming from SARS-CoV-2-induced immune responses or vascular damage, which itself can arise due to direct infection of vascular cells or as a consequence of immune-mediated effects. In brains of deceased COVID-19 patients SARS-CoV-2 RNA was only occasionally detected at low levels and did not show any correlation to neuroinflammatory signatures indicative of virus replication within the CNS [8][9][10][11]. In rare cases, SARS-CoV-2 RNA was found in cerebrospinal fluid of living COVID-19 patients [1,[12][13][14]. Although confounding effects due to the interval between infection and sample acquisition, and lack of sequential sample collection cannot be excluded, these observations do not support significant neurotropism and replication of SARS-CoV-2 within the CNS. ...
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... Thus, it is essential to identify contributory pathological processes in early disease to prevent progression to dementia, disability, and death. An early process in AD, prior to clinical dementia, is a deficit in the sense of smell 1-3 accompanied by amyloid-beta (Aβ) deposition in the olfactory bulb (OB) 4,5 . The OB receives olfactory input from olfactory sensory neurons in the olfactory epithelium (OE) 3, 6 then transmits olfactory information via the olfactory tract (OT) to the entorhinal cortex and hippocampus, brain regions essential for learning and memory that are affected in AD. ...
... Pathologically, tau tangles accumulate first in the trans-entorhinal region (Braak and Braak, 1991); tau accumulation is one of the leading causes of neuronal death and a predictor of brain atrophy in AD (Malpetti et al., 2022;Planche et al., 2022). Although the olfactory bulb is also affected by tau pathology in early Braak stages (Kovacs et al., 1999), a post-mortem histological study showed that olfactory bulb tau pathology failed to predict olfactory identification (Tremblay et al., 2022), while other studies showed that olfactory identification would be associated with cerebrospinal fluid (CSF) tau pathology (Lafaille-Magnan et al., 2017;Reijs et al., 2017;Tu et al., 2020) and with tau pathology within medial-temporal lobe regions (Klein et al., 2021;Risacher et al., 2017). Accordingly, limbic and medial-temporal structures of the primary olfactory cortex (POC), which includes the piriform cortex, the amygdala, the olfactory nucleus, the olfactory tubercle, and the entorhinal cortex, are atrophied in patients with AD, raising the hypothesis that POC atrophy may be present as early as the MCI stage and being one of the main causes of the early olfactory identification impairment (Jobin et al., 2021a). ...
... The UDS3NB has a validated factors structure in cognitively intact older adults (Kiselica et al., 2020a) and exhibits convergent and ecological validity in samples of individuals with neurologicalcompromise (e.g., Parkinson's disease) (Lea et al., 2021). To maximize sample size and external validity for individuals that are too cognitively/behaviorally impaired to complete all measures within a comprehensive neuropsychological battery, missing UDS3NB data points due to cognitive/behavioral issues were recoded using established methods (Heaton, 2004). ...
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... The current study was also limited by the lack of peripheral tissues paired with SNpc tissue for gingipain analysis. Future studies would bene t from the analysis of gingipains in peripheral tissues known to harbor αSyn pathology, including submandibular gland 52 , esophagus 53 , stomach 54 , vermiform appendix 55 , colon 56 , and peripheral nerve. 57 In summary, the ndings of this study offer evidence that gingipains from P. gingivalis may accumulate in the SNpc of the human brain. ...