Showing papers by "Kenneth M. Heilman published in 2020"
TL;DR: It is proposed that in conjunction with current diagnostic criteria, statistical modeling techniques using neuropsychological test performance should be leveraged to construct a system to classify AD/VaD spectrum dementia in order to test hypotheses regarding how mechanisms related to AD and VaD pathology interact and influence each other.
Abstract: Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common types of dementia. Although the combination of these disorders, called 'mixed' dementia, is recognized, the prevailing clinical and research perspective continues to consider AD and VaD as independent disorders. A review of recent neuropathological and neuropsychological literature reveals that these two disorders frequently co-occur and so-called 'pure' AD or VaD is comparatively rare. In addition, recent research shows that vascular dysfunction not only potentiates AD pathology, but that pathological changes in AD may subsequently induce vascular disorders. On the basis of these data, we propose that the neurobiological underpinnings underlying AD/VaD dementia and their neuropsychological phenotypes are best understood as existing along a clinical/pathological continuum or spectrum. We further propose that in conjunction with current diagnostic criteria, statistical modeling techniques using neuropsychological test performance should be leveraged to construct a system to classify AD/VaD spectrum dementia in order to test hypotheses regarding how mechanisms related to AD and VaD pathology interact and influence each other.
42 citations
TL;DR: MCI is highly prevalent in the early stage of motor-manifest HD, suggesting at the earlier stage of this disease the frontal-striatal-executive and/or the temporoparietal-representational functional network can be impaired.
27 citations
TL;DR: To determine the relationships between the motor phenotype and the presence of specific neuropsychiatric and neuropsychological disorders in patients with early motor‐manifest Huntington's disease (HD).
Abstract: OBJECTIVE To determine the relationships between the motor phenotype and the presence of specific neuropsychiatric and neuropsychological disorders in patients with early motor-manifest Huntington's disease (HD). METHODS From the Enroll-HD study, 3,505 individuals with HD who had ≤5 years of motor symptoms were classified based on the predefined parkinsonism/chorea index into chorea-dominant (n = 1125), parkinsonism-dominant (n = 867), and mixed-motor phenotype (n = 1513) groups. An analysis was performed on the results of the short Problem Behaviors Assessment. This test assesses patients for neuropsychiatric disorders such as depression, irritability/aggression, apathy, obsessive-compulsive behaviors, and psychosis as well as cognitive disorders by using neuropsychological tests such as the Stroop Interference test, Trail Making Test Part A and B, letter fluency, Symbol Digit Modality test, and animal fluency test. RESULTS In these early motor-manifest HD individuals, motor phenotype was associated with neuropsychiatric and cognitive changes. Independent of the age of motor onset, motor duration and severity, CAG repeat expansion, and medication use, the parkinsonism-dominant group had more severe neuropsychiatric disorders (depression, apathy, obsessive-compulsive behaviors, and psychosis) and poorer performance on all cognitive tests than those patients in the mixed-motor phenotype and chorea-dominant groups. The patients in the chorea-dominant group had less apathy and depression than those in the mixed-motor phenotype group. CONCLUSIONS In the early stage of motor-manifest HD, parkinsonism-dominant patients appear to have more severe neuropsychiatric disturbances and more cognitive impairments than those HD patients with chorea-dominant and mixed-motor phenotypes. Future studies should explore the brain mechanisms of these disorders and the possible treatments. © 2020 International Parkinson and Movement Disorder Society.
14 citations
TL;DR: In this article, the authors explored differences in distribution of white matter hyperintensities (called leukoaraiosis; LA) in older adults with atrial fibrillation (AF) vs. non-AF peers measured by: (1) depth distribution; (2) anterior-posterior distribution; associations between LA and cortical thickness; and (4) presence of lacunae and stroke.
Abstract: Background This pilot study explored differences in distribution of white matter hyperintensities (called leukoaraiosis; LA) in older adults (mean age = 67 years) with atrial fibrillation (AF) vs. non-AF peers measured by: (1) depth distribution; (2) anterior-posterior distribution; (3) associations between LA and cortical thickness; and (4) presence of lacunae and stroke. Methods Participant data (AF n = 17; non-AF peers n = 17) were acquired with the same magnetic resonance imaging protocols. LA volume was quantified by cortical depth (periventricular, deep, infracortical) and in anterior and posterior regions. Cortical thickness by lobe was assessed relative to LA load. Results Relative to non-AF peers, the AF group had twice the total LA volume (AF = 2.1% vs. Non-AF = 0.9%), over 10 times greater infracortical LA (AF = 0.72% vs. Non-AF = 0.07%), and three times greater deep LA (AF = 2.1% vs. Non-AF = 0.6%). Examinations of the extent of LA in anterior vs. posterior regions revealed a trend for more posterior relative to anterior LA. In the entire sample, total LA and infracortical LA were negatively associated with temporal lobe thickness. Only those with AF presented with lacunae or stroke. Conclusion Aging adults with AF had more total white matter disease than those without AF, particularly near the cortical mantle and deep within the cortex. Total and infracortical white matter disease in the entire sample negatively associated with temporal lobe thickness. Results suggest that those with AF have a distinct pattern of LA relative to those without AF, and that LA severity for all individuals may associate with structural changes in the cortex.
5 citations
TL;DR: Research associating responding to oblique versus non-oblique test stimuli using additional neuropsychological test paradigms, and MRI-defined neuroanatomical regions of interest may provide additional information about the brain-behavior relations that underlie MCI subtypes.
Abstract: Introduction: The Oblique Effect denotes superior performance for perceiving horizontal or vertical rather than diagonal or oblique stimuli. The current research investigated responding to oblique ...
5 citations
TL;DR: The four types of apraxia that can be associated with Parkinson's disease are reviewed, how they can be tested, the disabilities associated with these disorders and possible treatments are reviewed.
4 citations
TL;DR: The results provide support for both the right hemisphere spatial-attentional dominance hypothesis of pseudoneglect and the right hemi-aging hypotheses.
Abstract: Leftward deviation on a horizontal line bisection test (pseudoneglect) might be induced by right hemispheric dominance for mediating spatial or global attention, or a hemispheric asymmetry in the a...
4 citations
TL;DR: Findings suggest that m/sTBI survivors exhibit this loss of normal upward attentional bias, as alteration of spatial attention can be a major cause of disability.
Abstract: Objective: Research on impairments of spatial attention has primarily investigated hemispatial neglect in brain-lesioned patients, revealing decrements in the allocation of attention to right versu...
4 citations
TL;DR: Injuries to the right temporal lobe may account for a 72-year-old, right-handed male who developed transient left hemiparesis's upward neglect with downward deviation, and further studies are needed to better understand the pathophysiology of vertical neglect.
Abstract: Individuals with a hemispheric infarction often reveal inattention to, or neglect of, contralesional lateral space (ie, hemispatial neglect). Individuals with a bilateral ventral temporal-occipital lesion have been shown to demonstrate upper vertical neglect, and those with a bilateral parietal-occipital lesion have been shown to demonstrate lower vertical neglect. However, to our knowledge, there have been no reports of individuals with vertical neglect from a unilateral hemispheric lesion. We report on a 72-year-old, right-handed male who developed transient left hemiparesis. On examination, he had left facial weakness and he bisected horizontal lines to the left of the midline (ie, ipsilesional neglect). In addition, on a line bisection test involving nine vertical line bisections, he demonstrated downward deviation in the majority of the trials; healthy individuals deviate upward. On brain imaging, our patient revealed a cerebral infarction, primarily affecting the right temporal lobe; the temporal lobes contain the ventral attentional network that allocates attention upward. There is also some evidence that, whereas the right hemisphere mediates attention upward, the left mediates attention downward. Therefore, injury to the right temporal lobe may account for our patient's upward neglect with downward deviation. However, further studies are needed to better understand the pathophysiology of vertical neglect.
4 citations
TL;DR: A patient who in the absence of these disorders developed musical hallucinations from an infarction of the right hemisphere that primarily injured his right frontal and anterior temporal lobes is presented.
Abstract: have been reported in association with psychiatric diseases, brain stem strokes, deafness, degenerative diseases, intoxications, pharmacologic agents, and epilepsy. We present a patient who in the ...
1 citations
TL;DR: Depressive symptoms may be associated with a relative lowering of the vertical attentional bias, and this lowering may be related to increased activation of portions of the default network.
Abstract: BACKGROUND Emotions and moods are often expressed using verbal, vertical spatial metaphors (eg, "I'm feeling down"). The reason for using these vertical metaphors is unknown; however, when individuals experience depressive symptoms, they often become self-reflective and ruminative. These mental activities are associated with activation of the default network, including the parietal lobes. The parietal lobes are a critical component of the dorsal visual attentional network, which allocates attention downward. Therefore, activation of the default network may create a downward bias of vertical attention. OBJECTIVE To investigate whether depressive mood disposition, as measured by the number of depressive symptoms experienced by an individual, influences their allocation of vertical attention. METHODS We used the Hospital Anxiety and Depression Scale to evaluate depressive symptoms in 48 right-handed individuals with a mean age of 57.31 (±17.14) years. We also asked the participants to mark the center (bisect) of 24 vertical and 24 horizontal lines. RESULTS Overall, the individuals deviated their bisections of vertical lines upward (M=2.66 mm; SD=3.85). A stepwise linear regression analysis revealed that the number of depressive symptoms an individual experienced was significantly associated with a reduction in the magnitude of this upward vertical bias (P=0.009; R=0.138), such that the number of depressive symptoms was associated with the reduction (lowering) of their upward bias. CONCLUSION Depressive symptoms may be associated with a relative lowering of the vertical attentional bias, and this lowering may be related to increased activation of portions of the default network.
23 Mar 2020
TL;DR: It is submitted that models associating phenotypic features— largely defined using neuropsychological tests— coupled with the quantification of underlying biological substrate would be a more heuristically meaningful method for AD/ VaD classification.
Abstract: The prevailing point of view suggests that Alzheimer’s disease (AD) and vascular dementia (VaD) are independent forms of dementia. However, over the last decade a robust and emerging body of research has shown that many patients diagnosed with either AD or VaD present with biological substrates associated with both dementia syndromes to suggest considerable pathological and clinical heterogeneity. The notion that the pathological changes associated with these two disorders are additive, synergistic, or directly related to each other is the subject of lively debate (Esiri et al., 1999; Sweeney et al., 2019). An emerging challenge regarding the classification of these disorders is not necessarily the diagnosis of a specific clinical/ pathological syndrome; rather, determining how much or what proportion of a patient’s clinical or phenotypic presentation is associated with what type of underlying neuropathology. The determination of how much or what proportion requires an inclusive algorithm that defines meaningful neuropsychological phenotypes along with biological indicators of dementia obtained from imaging and fluid biomarkers. This type of algorithm for classifying AD/ VaD spectrum dementia is very different from current dementia diagnostic schemes where the presence of a single fluid biomarker or a positive finding from an imaging study determines the diagnosis (Jack et al., 2018). We would submit that models associating phenotypic features— largely defined using neuropsychological tests— coupled with the quantification of underlying biological substrate would be a more heuristically meaningful method for AD/ VaD classification. This type of algorithm, gaining traction in the literature (Bondi et al., 2014; Edmonds et al., 2015, 2019; Eppig et al., 2012; Libon et al., 2010, 2011; 2014; Wong et al., 2018), is particularly relevant for selecting patients and formulating expected outcomes for clinical trials designed to treat dementia (Edmonds et al., 2018).
TL;DR: This patient with probable posterior cortical atrophy who demonstrated lower right-sided quadrantic visuospatial neglect, together with allocentric vertical neglect, illustrates the importance of evaluating patients for these and other forms of neglect.
TL;DR: A left-handed man diagnosed with corticobasal syndrome who had a two-year history of progressive agraphia was evaluated and his performance on sentence writing and clock drawing tasks revealed an increase of movement errors as the tasks progressed.
Abstract: Proactive interference is when a previously performed task impairs performance on a current task. It is often associated with memory tasks and has not been reported to interfere with writing or dra...
TL;DR: Patients with degenerative dementia, especially those with similar patterns of leukoaraiosis or parietal degeneration should be tested for vertical and radial forms of spatial neglect.
Abstract: A 75 year-old man had a two-year history of progressive memory loss, trouble with finances and getting lost. On examination, he scored 16/30 in MoCA test, noticeably impaired on the attentional tasks. His screening bloodtests werenormal. Brain imaging revealed hippocampal atrophy and bilaterallarge areas of leukoaraiosis below posterior parietal lobes. On vertical line bisection he revealed a large upward bias and on radial bisection, a distal bias. Degeneration of his posterior parietal cortex may have caused both the leukoaraiosis and vertical-radial neglect. Unawareness of portions of space can be a source of disability and cause injury. Therefore, patients with degenerative dementia, especially those with similar patterns of leukoaraiosis or parietal degeneration should be tested for vertical and radial forms of spatial neglect.
01 Jan 2020
TL;DR: This chapter summarizes the means of testing for these different forms of apraxia, the types of errors made by patients with these forms of ApraxIA, and the pathophysiology and treatment of these disorders.
Abstract: Apraxia is a disorder of the skilled movements that are needed successfully perform transitive or intransitive movements, when this disorder is not caused by failures of comprehension, weakness, sensory loss, or involuntary movements. The following forms of upper limb apraxia have been reported to be associated with Parkinson's disease: (1) limb-kinetic apraxia, a loss of the ability to make precise, independent but coordinated finger-hand movements; (2) ideomotor apraxia, a failure to make the correct joint movements, to coordinate these movements with the correct timing, speed, and force; and (3) ideational apraxia, the incorrect sequencing of a series of actions required to complete a goal. This chapter summarizes the means of testing for these different forms of apraxia, the types of errors made by patients with these forms of apraxia, and the pathophysiology and treatment of these disorders.