Research Priorities of Individuals and Caregivers With Lewy Body Dementia: A Web-based Survey.

INTRODUCTION: Lewy body dementia (LBD) is common, yet under-recognized and under-researched. To plan studies with the highest impact, engagement of the community personally affected by these conditions is essential. METHODS: A web-based survey of people living with LBD and current and former caregivers of people with LBD queried research priorities through forced ranking and exploration of burden of LBD symptoms. Specific caregiving needs in LBD and perceptions of research participation were also investigated. RESULTS: Between April 7, 2021 and July 1, 2021, 984 responses were recorded. Top research priorities included disease-modifying therapies and improved disease detection and staging. People with LBD were interested in pathophysiology and more bothered by motor symptoms; caregivers were interested in risk factors and symptomatic therapies and more bothered by neuropsychiatric symptoms. Few available LBD treatments and resources were rated as helpful, and many valuable services were never received. Previous participation in LBD research was infrequent, but interest was high. DISCUSSION: People with LBD and caregivers highlighted the need for research across all aspects of LBD, from pathophysiology and disease modification to prognosis, education, symptomatic treatments, and caregiver support. Funders should increase support for all aspects of LBD research to target the many needs identified by individuals and families living with LBD.

Axonal Tract Reconstruction Using a Tissue-Engineered Nigrostriatal Pathway in a Rat Model of Parkinson's Disease.

Parkinson's disease (PD) affects 1-2% of people over 65, causing significant morbidity across a progressive disease course. The classic PD motor deficits are caused by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in the loss of their long-distance axonal projections that modulate striatal output. While contemporary treatments temporarily alleviate symptoms of this disconnection, there is no approach able to replace the nigrostriatal pathway. We applied microtissue engineering techniques to create a living, implantable tissue-engineered nigrostriatal pathway (TE-NSP) that mimics the architecture and function of the native pathway. TE-NSPs comprise a discrete population of dopaminergic neurons extending long, bundled axonal tracts within the lumen of hydrogel micro-columns. Neurons were isolated from the ventral mesencephalon of transgenic rats selectively expressing the green fluorescent protein in dopaminergic neurons with subsequent fluorescent-activated cell sorting to enrich a population to 60% purity. The lumen extracellular matrix and growth factors were varied to optimize cytoarchitecture and neurite length, while immunocytochemistry and fast-scan cyclic voltammetry (FSCV) revealed that TE-NSP axons released dopamine and integrated with striatal neurons in vitro. Finally, TE-NSPs were implanted to span the nigrostriatal pathway in a rat PD model with a unilateral 6-hydroxydopamine SNpc lesion. Immunohistochemistry and FSCV established that transplanted TE-NSPs survived, maintained their axonal tract projections, extended dopaminergic neurites into host tissue, and released dopamine in the striatum. This work showed proof of concept that TE-NSPs can reconstruct the nigrostriatal pathway, providing motivation for future studies evaluating potential functional benefits and long-term durability of this strategy. This pathway reconstruction strategy may ultimately replace lost neuroarchitecture and alleviate the cause of motor symptoms for PD patients.

Mossy cell hypertrophy and synaptic changes in the hilus following mild diffuse traumatic brain injury in pigs.

BACKGROUND: Each year in the USA, over 2.4 million people experience mild traumatic brain injury (TBI), which can induce long-term neurological deficits. The dentate gyrus of the hippocampus is notably susceptible to damage following TBI, as hilar mossy cell changes in particular may contribute to post-TBI dysfunction. Moreover, microglial activation after TBI may play a role in hippocampal circuit and/or synaptic remodeling; however, the potential effects of chronic microglial changes are currently unknown. The objective of the current study was to assess neuropathological and neuroinflammatory changes in subregions of the dentate gyrus at acute to chronic time points following mild TBI using an established model of closed-head rotational acceleration induced TBI in pigs. METHODS: This study utilized archival tissue of pigs which were subjected to sham conditions or rapid head rotation in the coronal plane to generate mild TBI. A quantitative assessment of neuropathological changes in the hippocampus was performed via immunohistochemical labeling of whole coronal tissue sections at 3 days post-injury (DPI), 7 DPI, 30 DPI, and 1 year post-injury (YPI), with a focus on mossy cell atrophy and synaptic reorganization, in context with microglial alterations (e.g., density, proximity to mossy cells) in the dentate gyrus. RESULTS: There were no changes in mossy cell density between sham and injured animals, indicating no frank loss of mossy cells at the mild injury level evaluated. However, we found significant mossy cell hypertrophy at 7 DPI and 30 DPI in anterior (> 16% increase in mean cell area at each time; p = <  0.001 each) and 30 DPI in posterior (8.3% increase; p = <  0.0001) hippocampus. We also found dramatic increases in synapsin staining around mossy cells at 7 DPI in both anterior (74.7% increase in synapsin labeling; p = <  0.0001) and posterior (82.7% increase; p = < 0.0001) hippocampus. Interestingly, these morphological and synaptic alterations correlated with a significant change in microglia in proximity to mossy cells at 7 DPI in anterior and at 30 DPI in the posterior hippocampus. For broader context, while we found that there were significant increases in microglia density in the granule cell layer at 30 DPI (anterior and posterior) and 1 YPI (posterior only) and in the molecular layer at 1 YPI (anterior only), we found no significant changes in overall microglial density in the hilus at any of the time points evaluated post-injury. CONCLUSIONS: The alterations of mossy cell size and synaptic inputs paired with changes in microglia density around the cells demonstrate the susceptibility of hilar mossy cells after even mild TBI. This subtle hilar mossy cell pathology may play a role in aberrant hippocampal function post-TBI, although additional studies are needed to characterize potential physiological and cognitive alterations.

Cognitive and Pathological Influences of Tau Pathology in Lewy Body Disorders.

OBJECTIVE: To use digital histology in a large autopsy cohort of Lewy body disorder (LBD) patients with dementia to test the hypotheses that co-occurring Alzheimer disease (AD) pathology impacts the anatomic distribution of α-synuclein (SYN) pathology and that co-occurring neocortical tau pathology in LBDs associates with worse cognitive performance and occurs in a pattern differing from AD. METHODS: Fifty-five autopsy-confirmed LBD (Parkinson disease with dementia, n = 36; dementia with Lewy bodies, n = 19) patients and 25 AD patients were studied. LBD patients were categorized as having moderate/severe AD copathology (SYN + AD = 20) or little/no AD copathology (SYN-AD = 35). Digital measures of tau, ß-amyloid (Aß), and SYN histopathology in neocortical and subcortical/limbic regions were compared between groups and related to antemortem cognitive testing. RESULTS: SYN burden was higher in SYN + AD than SYN-AD in each neocortical region (F1, 54 = 5.6-6.0, p < 0.02) but was equivalent in entorhinal cortex and putamen (F1, 43-49 = 0.7-1.7, p > 0.2). SYN + AD performed worse than SYN-AD on a temporal lobe-mediated naming task (t27 = 2.1, p = 0.04). Antemortem cognitive test scores inversely correlated with tau burden (r = -0.39 to -0.68, p < 0.05). AD had higher tau than SYN + AD in all regions (F1, 43 = 12.8-97.2, p < 0.001); however, SYN + AD had a greater proportion of tau in the temporal neocortex than AD (t41 = 2.0, p < 0.05), whereas AD had a greater proportion of tau in the frontal neocortex than SYN + AD (t41 = 3.3, p < 0.002). SYN + AD had similar severity and distribution of neocortical Aß compared to AD (F1, 40-43 = 1.6-2.0, p > 0.1). INTERPRETATION: LBD patients with AD copathology harbor greater neocortical SYN pathology. Regional tau pathology relates to cognitive performance in LBD dementia, and its distribution may diverge from pure AD. Tau copathology contributes uniquely to the heterogeneity of cognitive impairment in LBD. Ann Neurol 2018; 1-13 ANN NEUROL 2019;85:259-271.

Subjective Cognitive Complaint in Parkinson's Disease Patients With Normal Cognition: Canary in the Coal Mine?

OBJECTIVE: The objective of this study was to determine the frequency and impact of subjective cognitive complaint (SCC) in Parkinson's disease (PD) patients with normal cognition. METHODS: Patients with PD with expert consensus-determined normal cognition at baseline were asked a single question regarding the presence of SCC. Baseline (N = 153) and longitudinal (up to 4 follow-up visits during a 5-year period; N = 121) between-group differences in patients with PD with (+SCC) and without (-SCC) cognitive complaint were examined, including cognitive test performance and self-rated and informant-rated functional abilities. RESULTS: A total of 81 (53%) participants reported a cognitive complaint. There were no between-group differences in global cognition at baseline. Longitudinally, the +SCC group declined more than the -SCC group on global cognition (Mattis Dementia Rating Scale-2 total score, F1,431 = 5.71, P = 0.02), processing speed (Symbol Digit Modalities Test, F1,425 = 7.52, P = 0.006), and executive function (Trail Making Test Part B, F1,419 = 4.48, P = 0.04), although the results were not significant after correction for multiple testing. In addition, the +SCC group was more likely to progress to a diagnosis of cognitive impairment over time (hazard ratio = 2.61, P = 0.02). The +SCC group also demonstrated significantly lower self-reported and knowledgeable informant-reported cognition-related functional abilities at baseline, and declined more on an assessment of global functional abilities longitudinally. CONCLUSIONS: Patients with PD with normal cognition, but with SCC, report poorer cognition-specific functional abilities, and are more likely to be diagnosed with cognitive impairment and experience global functional ability decline long term. These findings suggest that SCC and worse cognition-related functional abilities may be sensitive indicators of initial cognitive decline in PD. © 2020 International Parkinson and Movement Disorder Society.

Association of brain heptachlor epoxide and other organochlorine compounds with lewy pathology.

BACKGROUND: Organochlorine pesticides are associated with an increased risk of Parkinson's disease. A preliminary analysis from the Honolulu-Asia Aging Study suggested that heptachlor epoxide, a metabolite from an organochlorine pesticide extensively used in Hawaii, may be especially important. This was a cross sectional analysis to evaluate the association of heptachlor epoxide and other organochlorine compounds with Lewy pathology in an expanded survey of brain organochlorine residues from the longitudinal Honolulu-Asia Aging Study. METHODS: Organochlorines were measured in frozen occipital or temporal lobes in 705 brains using gas chromatography with mass spectrometry. Lewy pathology was identified using hematoxylin and eosin- and α-synuclein immunochemistry-stained sections from multiple brain regions. RESULTS: The prevalence of Lewy pathology was nearly doubled in the presence versus the absence of heptachlor epoxide (30.1% versus 16.3%, P < 0.001). Although associations with other compounds were weaker, hexachlorobenzene (P = 0.003) and α-chlordane (P = 0.007) were also related to Lewy pathology. Most of the latter associations, however, were a result of confounding from heptachlor epoxide. Neither compound was significantly related to Lewy pathology after adjustment for heptachlor epoxide. In contrast, the association of heptachlor epoxide with Lewy pathology remained significant after adjustments for hexachlorobenzene (P = 0.013) or α-chlordane (P = 0.005). Findings were unchanged after removal of cases of PD and adjustment for age and other characteristics. CONCLUSIONS: Organochlorine pesticides are associated with the presence of Lewy pathology in the brain, even after exclusion of PD cases. Although most of the association is through heptachlor epoxide, the role of other organochlorine compounds is in need of clarification. © 2018 International Parkinson and Movement Disorder Society.

Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated.

Lewy bodies commonly occur in Alzheimer's disease, and Alzheimer's disease pathology is frequent in Lewy body diseases, but the burden of co-pathologies across neurodegenerative diseases is unknown. We assessed the extent of tau, amyloid-ß, α-synuclein and TDP-43 proteinopathies in 766 autopsied individuals representing a broad spectrum of clinical neurodegenerative disease. We interrogated pathological Alzheimer's disease (n = 247); other tauopathies (n = 95) including Pick's disease, corticobasal disease and progressive supranuclear palsy; the synucleinopathies (n = 164) including multiple system atrophy and Lewy body disease; the TDP-43 proteinopathies (n = 188) including frontotemporal lobar degeneration with TDP-43 inclusions and amyotrophic lateral sclerosis; and a minimal pathology group (n = 72). Each group was divided into subgroups without or with co-pathologies. Age and sex matched logistic regression models compared co-pathology prevalence between groups. Co-pathology prevalence was similar between the minimal pathology group and most neurodegenerative diseases for each proteinopathy: tau was nearly universal (92-100%), amyloid-ß common (20-57%); α-synuclein less common (4-16%); and TDP-43 the rarest (0-16%). In several neurodegenerative diseases, co-pathology increased: in Alzheimer's disease, α-synuclein (41-55%) and TDP-43 (33-40%) increased; in progressive supranuclear palsy, α-synuclein increased (22%); in corticobasal disease, TDP-43 increased (24%); and in neocortical Lewy body disease, amyloid-ß (80%) and TDP-43 (22%) increased. Total co-pathology prevalence varied across groups (27-68%), and was increased in high Alzheimer's disease, progressive supranuclear palsy, and neocortical Lewy body disease (70-81%). Increased age at death was observed in the minimal pathology group, amyotrophic lateral sclerosis, and multiple system atrophy cases with co-pathologies. In amyotrophic lateral sclerosis and neocortical Lewy body disease, co-pathologies associated with APOE ɛ4. Lewy body disease cases with Alzheimer's disease co-pathology had substantially lower Mini-Mental State Examination scores than pure Lewy body disease. Our data imply that increased age and APOE ɛ4 status are risk factors for co-pathologies independent of neurodegenerative disease; that neurodegenerative disease severity influences co-pathology as evidenced by the prevalence of co-pathology in high Alzheimer's disease and neocortical Lewy body disease, but not intermediate Alzheimer's disease or limbic Lewy body disease; and that tau and α-synuclein strains may also modify co-pathologies since tauopathies and synucleinopathies had differing co-pathologies and burdens. These findings have implications for clinical trials that focus on monotherapies targeting tau, amyloid-ß, α-synuclein and TDP-43.

The prodromal phase of leucine-rich repeat kinase 2-associated Parkinson disease: Clinical and imaging Studies.

BACKGROUND: Asymptomatic, nonmanifesting carriers of leucine-rich repeat kinase 2 mutations are at increased risk of developing PD. Clinical and neuroimaging features may be associated with gene carriage and/or may demarcate individuals at greater risk for phenoconversion to PD. OBJECTIVES: To investigate clinical and dopamine transporter single-photon emission computed tomography imaging characteristics of leucine-rich repeat kinase 2 asymptomatic carriers. METHODS: A total of 342 carriers' and 259 noncarriers' relatives of G2019S leucine-rich repeat kinase 2/PD patients and 39 carriers' and 31 noncarriers' relatives of R1441G leucine-rich repeat kinase 2/PD patients were evaluated. Motor and nonmotor symptoms were assessed using specific scales and questionnaires. Neuroimaging quantitative data were obtained in 81 carriers and compared with 41 noncarriers. RESULTS: G2019S carriers scored higher in motor scores and had lower radioligand uptake compared to noncarriers, but no differences in nonmotor symptoms scores were observed. R1441G carriers scored higher in motor scores, had lower radioligand uptake, and had higher scores in depression, dysautonomia, and Rapid Eye Movements Sleep Behavior Disorder Screening Questionnaire scores, but had better cognition scores than noncarriers. Among G2019S carriers, a group with "mild motor signs" was identified, and was significantly older, with worse olfaction and lower radioligand uptake. CONCLUSIONS: G2019S and R1441G carriers differ from their noncarriers' relatives in higher motor scores and slightly lower radioligand uptake. Nonmotor symptoms were mild, and different nonmotor profiles were observed in G2019S carriers compared to R1441G carriers. A group of G2019S carriers with known prodromal features was identified. Longitudinal studies are required to determine whether such individuals are at short-term risk of developing overt parkinsonism. © 2017 International Parkinson and Movement Disorder Society.

Preclinical modelling of militarily relevant traumatic brain injuries: Challenges and recommendations for future directions.

As a follow-up to the 2008 state-of-the-art (SOTA) conference on traumatic brain injuries (TBIs), the 2015 event organized by the United States Department of Veterans Affairs (VA) Office of Research and Development (ORD) analysed the knowledge gained over the last 7 years as it relates to basic scientific methods, experimental findings, diagnosis, therapy, and rehabilitation of TBIs and blast-induced neurotraumas (BINTs). The current article summarizes the discussions and recommendations of the scientific panel attending the Preclinical Modeling and Therapeutic Development Workshop of the conference, with special emphasis on factors slowing research progress and recommendations for ways of addressing the most significant pitfalls.

Pathological α-synuclein distribution in subjects with coincident Alzheimer's and Lewy body pathology.

We investigated the distribution patterns of Lewy body-related pathology (LRP) and the effect of coincident Alzheimer disease (AD) pathology using a data-driven clustering approach that identified groups with different LRP pathology distributions without any diagnostic or researcher's input in two cohorts including: Parkinson disease patients without (PD, n = 141) and with AD (PD-AD, n = 80), dementia with Lewy bodies subjects without AD (DLB, n = 13) and demented subjects with AD and LRP pathology (Dem-AD-LB, n = 308). The Dem-AD-LB group presented two LRP patterns, olfactory-amygdala and limbic LRP with negligible brainstem pathology, that were absent in the PD groups, which are not currently included in the DLB staging system and lacked extracranial LRP as opposed to the PD group. The Dem-AD-LB individuals showed relative preservation of substantia nigra cells and dopamine active transporter in putamen. PD cases with AD pathology showed increased LRP. The cluster with occipital LRP was associated with non-AD type dementia clinical diagnosis in the Dem-AD-LB group and a faster progression to dementia in the PD groups. We found that (1) LRP pathology in Dem-AD-LB shows a distribution that differs from PD, without significant brainstem or extracranial LRP in initial phases; (2) coincident AD pathology is associated with increased LRP in PD indicating an interaction; (3) LRP and coincident AD pathology independently predict progression to dementia in PD, and (4) evaluation of LRP needs to acknowledge different LRP spreading patterns and evaluate substantia nigra integrity in the neuropathological assessment and consider the implications of neuropathological heterogeneity for clinical and biomarker characterization.

Defining and validating a short form Montreal Cognitive Assessment (s-MoCA) for use in neurodegenerative disease.

INTRODUCTION: Screening for cognitive deficits is essential in neurodegenerative disease. Screening tests, such as the Montreal Cognitive Assessment (MoCA), are easily administered, correlate with neuropsychological performance and demonstrate diagnostic utility. Yet, administration time is too long for many clinical settings. METHODS: Item response theory and computerised adaptive testing simulation were employed to establish an abbreviated MoCA in 1850 well-characterised community-dwelling individuals with and without neurodegenerative disease. RESULTS: 8 MoCA items with high item discrimination and appropriate difficulty were identified for use in a short form (s-MoCA). The s-MoCA was highly correlated with the original MoCA, showed robust diagnostic classification and cross-validation procedures substantiated these items. DISCUSSION: Early detection of cognitive impairment is an important clinical and public health concern, but administration of screening measures is limited by time constraints in demanding clinical settings. Here, we provide as-MoCA that is valid across neurological disorders and can be administered in approximately 5 min.

Motor and nonmotor heterogeneity of LRRK2-related and idiopathic Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) associated with LRRK2 mutations has been described as similar to idiopathic PD with minor clinical differences. No study has compared the clinical features of LRRK2-associated PD due to different mutations. The objective of this study was to compare LRRK2-associated PD due to G2019S and G2385R mutations and to compare each to idiopathic PD. METHODS: Sites within the international LRRK2 Cohort Consortium undertook family-based, community-based, or clinic-based studies to gather clinical data on manifesting carriers and patients with idiopathic PD. RESULTS: Five hundred sixteen PD patients with the G2019S mutation, 199 with the G2385R mutation, and 790 patients with idiopathic PD were included in the data set. Adjusted for age, sex, disease duration, and levodopa-equivalent daily dose, mean MDS-UPDRS part II or III scores and the frequency of motor fluctuations were higher in the G2385R mutation carriers than in either the G2019S mutation carriers or idiopathic PD patients. G2019S mutation carriers had significantly lower UPDRS part III scores than idiopathic PD patients. Both G2019S and G2385R mutation carriers had a higher proportion of the postural instability gait disorder phenotype compared with idiopathic PD patients. LRRK2 G2019S PD patients had better UPSIT scores and lower Geriatric Depression Scale scores than idiopathic PD patients in adjusted analyses. CONCLUSIONS: G2385R and G2019S PD appear to have motor differences that may be explained by contrasting local treatment or measurement practices or differences in the biology of the disease. Longitudinal studies should evaluate whether progression is faster in G2385R mutation carriers compared with G2019S PD or idiopathic PD. © 2016 International Parkinson and Movement Disorder Society.

Development and initial testing of the Penn Parkinson's Daily Activities Questionnaire.

OBJECTIVE: The aim of this work was to describe the development and psychometric analysis of the Penn Parkinson's Daily Activities Questionnaire. The questionnaire is an item response theory-based tool for rating cognitive instrumental activities of daily living in PD. METHODS: Candidate items for the Penn Parkinson's Daily Activities Questionnaire were developed through literature review and focus groups of patients and knowledgeable informants. Item selection and calibration of item-response theory parameters were performed using responses from a cohort of PD patients and knowledgeable informants (n = 388). In independent cohorts of PD patients and knowledgeable informants, assessments of test-retest reliability (n = 50), and construct validity (n = 68) of the questionnaire were subsequently performed. Construct validity was assessed by correlating questionnaire scores with measures of motor function, cognition, an existing activities of daily living measure, and directly observed daily function. RESULTS: Fifty items were retained in the final questionnaire item bank. Items were excluded owing to redundancy, difficult reading level, and when item-response theory parameters could not be calculated. Test-retest reliability was high (intraclass correlation coefficient = 0.97; P < 0.001). The questionnaire correlated strongly with cognition (r = 0.68; P < 0.001) and directly observed daily function (r = 0.87; P < 0.001), but not with motor impairment (r = 0.08; P = 0.53). The questionnaire score accurately discriminated between PD patients with and without dementia (receiver operating characteristic curve = 0.91; 95% confidence interval: 0.85-0.97). CONCLUSIONS: The Penn Parkinson's Daily Activities Questionnaire shows strong evidence of reliability and validity. Item response theory-based psychometric analysis suggests that this questionnaire can discriminate across a range of daily functions.

Arguing against the proposed definition changes of PD.

As members of the Lewy Body Dementia Association Scientific Advisory Council, we aim to address some of the issues raised in the article titled "Time to Redefine PD? Introductory Statement of the MDS Task Force on the Definition of Parkinson's Disease." In particular, we suggest that the 1-year rule distinguishing Parkinson's disease dementia from dementia with Lewy bodies is worth maintaining because it serves an important purpose in clinical practice and clinical and basic science research and when helping the lay community understand the complexity of these different clinical phenotypes. Furthermore, we believe that adding an additional diagnostic label, "PD (dementia with Lewy bodies subtype)," will confuse rather than clarify the distinction between dementia with Lewy bodies and PD or PD dementia, and will not improve management or expedite therapeutic development. We present arguments supporting our contentions. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Modifying Surface Energy of Graphene via Plasma-Based Chemical Functionalization to Tune Thermal and Electrical Transport at Metal Interfaces.

The high mobility exhibited by both supported and suspended graphene, as well as its large in-plane thermal conductivity, has generated much excitement across a variety of applications. As exciting as these properties are, one of the principal issues inhibiting the development of graphene technologies pertains to difficulties in engineering high-quality metal contacts on graphene. As device dimensions decrease, the thermal and electrical resistance at the metal/graphene interface plays a dominant role in degrading overall performance. Here we demonstrate the use of a low energy, electron-beam plasma to functionalize graphene with oxygen, fluorine, and nitrogen groups, as a method to tune the thermal and electrical transport properties across gold-single layer graphene (Au/SLG) interfaces. We find that while oxygen and nitrogen groups improve the thermal boundary conductance (hK) at the interface, their presence impairs electrical transport leading to increased contact resistance (ρC). Conversely, functionalization with fluorine has no impact on hK, yet ρC decreases with increasing coverage densities. These findings indicate exciting possibilities using plasma-based chemical functionalization to tailor the thermal and electrical transport properties of metal/2D material contacts.

Crossover from incoherent to coherent phonon scattering in epitaxial oxide superlattices.

Elementary particles such as electrons or photons are frequent subjects of wave-nature-driven investigations, unlike collective excitations such as phonons. The demonstration of wave-particle crossover, in terms of macroscopic properties, is crucial to the understanding and application of the wave behaviour of matter. We present an unambiguous demonstration of the theoretically predicted crossover from diffuse (particle-like) to specular (wave-like) phonon scattering in epitaxial oxide superlattices, manifested by a minimum in lattice thermal conductivity as a function of interface density. We do so by synthesizing superlattices of electrically insulating perovskite oxides and systematically varying the interface density, with unit-cell precision, using two different epitaxial-growth techniques. These observations open up opportunities for studies on the wave nature of phonons, particularly phonon interference effects, using oxide superlattices as model systems, with extensive applications in thermoelectrics and thermal management.

Motor phenotype of LRRK2-associated Parkinson's disease: a Tunisian longitudinal study.

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) were found to be a significant cause of late-onset autosomal dominant forms of Parkinson's disease (PD). To determine the motor characteristics of LRRK2-related disease, we conducted a longitudinal study of 58 G2019S LRRK2-associated PD patients and compared them with genetically undefined (GU) PD patients. Fifty-eight patients diagnosed with PD-related LRRK2 G2019S mutation were included in the study and compared with 54 sporadic PD patients with negative tests for LRRK2 G2019S, PINK1, SNCA, PRKN, and DJ1 mutations. Patients were assessed at baseline and after a follow-up period of 6 years. The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Hoehn and Yahr, and the Schwab and England scores were determined. Logistic regression was used to examine associations of G2019S mutation status with motor phenotype and rate of motor decline. The LRRK2-associated PD patients had a mean age of onset of 56.25 ± 12.05 years and in most cases (58.6%) a postural instability gait difficulty (PIGD) phenotype. The mean annual decline in the MDS-UDRS III motor score and the Hoehn and Yahr staging was of 1.3% and 2%, respectively. The PIGD phenotype predicted a more rapid progression of motor impairment. The PD motor phenotype and motor scores were similar in the LRRK2-associated PD group and in the GU PD group, with no significant differences in the progression rate of motor impairment. Motor phenotype seems to be similar in LRRK2-related PD and idiopathic PD.

Caregiver tele-support group for Parkinson's disease: A pilot study.

BACKGROUND: Parkinson's disease (PD) is a disabling neurodegenerative disease that typically affects the geriatric population and requires a caregiver. Although caregiver burden reduces quality of life of the caregiver, support groups for caregivers have not been studied. Offering a tele-support group to PD caregivers would be an innovative approach to extending a novel resource. METHODS: A single-center pilot study was conducted, enrolling caregivers in an 8-week tele-support group program. Mood state and caregiver burden were assessed at baseline and conclusion of the program using self-report questionnaires. Qualitative feedback was obtained at the conclusion of the program. RESULTS: Seven female spouse caregivers enrolled; 86% completed the program. Although no statistically significant changes in questionnaire scores were found, the mean Geriatric Depression Scale decreased from 4.2 to 3 and qualitative feedback was universally positive. CONCLUSIONS: The use of tele-support groups for PD caregivers is a feasible and innovative resource to address caregiver burden.

The spectrum of cognitive impairment in Lewy body diseases.

Cognitive impairment represents an important and often defining component of the clinical syndromes of Lewy body disorders: Parkinson's disease and dementia with Lewy bodies. The spectrum of cognitive deficits in these Lewy body diseases encompasses a broad range of clinical features, severity of impairment, and timing of presentation. It is now recognized that cognitive dysfunction occurs not only in more advanced Parkinson's disease but also in early, untreated patients and even in those patients with pre-motor syndromes, such as rapid eye movement behavior disorder and hyposmia. In recent years, the concept of mild cognitive impairment as a transitional or pre-dementia state in Parkinson's disease has emerged. This has led to much research regarding the diagnosis, prognosis, and underlying neurobiology of mild cognitive impairment in Parkinson's disease, but has also raised questions regarding the usefulness of this concept and its application in clinical and research settings. In addition, the conundrum of whether Parkinson's disease dementia and dementia with Lewy bodies represent the same or different entities remains unresolved. Although these disorders overlap in many aspects of their presentations and pathophysiology, they differ in other elements, such as timing of cognitive, behavioral, and motor symptoms; medication responses; and neuropathological contributions. This article examines the spectrum and evolution of cognitive impairment in Lewy body disorders and debates these controversial issues in the field using point-counterpoint approaches.