Caregiver Experiences and Burden in Moderate-Advanced Dementia With Lewy Bodies.

Background and Objectives: Dementia with Lewy bodies (DLB) is a common degenerative dementia, but research on caregiver experiences in late stages is lacking. This study aimed to investigate the caregiving experience in moderate-advanced DLB to identify opportunities for improving care and support. Methods: Dyads of individuals with moderate-advanced DLB and their primary informal caregivers were recruited from specialty clinics, advocacy organizations, and research registries. The study collected demographics, disease-related measures, and measures of the caregiver experience relating to caregiver support, burden, grief, self-efficacy, depression, quality of life, and coping. Spearman correlation coefficients and Wilcoxon rank-sum tests evaluated the relationships of caregiver measures with patient and caregiver variables with adjustments for multiple testing. Results: Caregivers (n = 143) were mostly women (83.5%) and spouses (84.7%) (mean age 68 years; range 37-85). Almost 40% reported high burden and/or depression. Caregiver measures correlated with fluctuation and behavioral symptom severity, sleepiness, and autonomic symptoms of the person with DLB. Higher burden correlated with worse caregiver quality of life, higher depression, and grief. Greater self-efficacy, social support, and resilience correlated with lower caregiver burden. The most frequently reported caregiver concerns were being unable to plan for the future, having to put the needs of the person with DLB ahead of the caregiver's own needs, and worry that the person with DLB would become too dependent on the caregiver, but many additional concerns were endorsed. Caregivers were generally satisfied with medical team support. The lowest reported satisfaction related to information regarding disease progression and how well medical teams shared information with each other. Discussion: Various patient-related and caregiver-related factors influence caregiver experiences in moderate-advanced DLB. Clinicians can target caregiver needs by providing support resources and DLB education and treating bothersome patient symptoms. Future research should investigate what interventions can modify and improve caregiver experiences in advanced DLB and identify therapeutics for patient symptoms currently without adequate treatments (e.g., fluctuations, daytime sleepiness). Trial Registration Information: NCT04829656.

Evaluating the efficacy of TeleFAMILIES: a telehealth intervention for caregivers of community-dwelling people with dementia.

Examine the efficacy of a telehealth-administered intervention for caregivers of persons with dementia.Two hundred sixteen caregivers engaged in the FAMILIES intervention over six months, either virtually (n = 59) or in-person (n = 157). The telehealth protocol (TeleFAMILIES) was conducted online. Caregivers engaged in six sessions, including individual and family/group counseling, ad hoc counseling, and had access to support groups. Sessions included person-centered assessments of caregivers' physical, emotional, social needs, and current support networks. Primary outcome variables were change in total score between baseline and completion on the Zarit Burden Interview (ZBI), Center for Epidemiologic Studies Depression Scale-Revised (CESD-R), and the Revised Memory and Behavior Problems Checklist (RMBPC).TeleFAMILIES caregivers reported significant reductions in ZBI (p = .002) and CESD-R scores (p < .001). RMBPC reaction scores significantly improved (p = .02) and improved more than in-person caregivers' scores (F (3, 119) = 2.71, p = .048, partial eta2 = .06). For those classified as having a higher risk of depression at baseline, a significantly larger portion TeleFAMILIES caregivers converted to a classification of lower depression risk at completion (p = .02).Compared to the in-person group, TeleFAMILIES caregivers experienced the same, if not greater improvements in perceived burden, depressive symptomatology, and their ability to manage their reactions to behavioral symptoms of dementia. The strengths of TeleFAMILIES are the convenience of telehealth services and its mitigation of barriers to care.

Feasibility and Preliminary Efficacy of an Internet-Delivered Intervention for Insomnia in Individuals with Mild Cognitive Impairment.

BACKGROUND: Approximately 50% of older adults with cognitive impairment suffer from insomnia. When untreated, pre-existing cognitive problems may be exacerbated and potentially contribute to further cognitive decline. One promising approach to maintain cognitive health is to improve sleep quantity and quality. OBJECTIVE: To determine feasibility, acceptability, and preliminary efficacy of Sleep Health Using the Internet for Older Adult Sufferers of Insomnia and Sleeplessness (SHUTi OASIS), an Internet-delivered cognitive behavioral therapy for insomnia (CBT-I) program in older adults with mild cognitive impairment (MCI). METHODS: Older adults with MCI and insomnia were recruited from hospital-based memory and sleep disorders clinics and enrolled in a single-arm pilot study. Participants completed the six cores of SHUTi OASIS, over nine weeks with two-week baseline and post-assessments using self-reported sleep diaries. Feasibility and acceptability were informed by usage statistics and qualitative interviews; preliminary efficacy was informed by patient-generated sleep data. RESULTS: Twelve participants enrolled and, on average, were 75.8 years of age. Ten participants completed the study and logged in most days. Most participants reported a positive overall experience, and interviews revealed successful and independent program management and completion. There were significant changes on all baseline to post-assessment sleep measures, including clinically meaningful improvements on the Insomnia Severity Index (13.5 to 8.3, p < 0.01), sleep efficiency, wake after sleep onset, and sleep onset latency (ps < 0.02). There was no statistically significant change in cognitive measures (p > 0.05). CONCLUSION: This study supports that older adults with cognitive impairment can independently complete CBT-I via the Internet and achieve clinical sleep improvements.

Fluid and Tissue Biomarkers of Lewy Body Dementia: Report of an LBDA Symposium.

The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health, and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer's pathology and novel biomarkers were discussed.

FAMILIES: an effective healthcare intervention for caregivers of community dwelling people living with dementia.

Objectives: Caregiving for a person with dementia (PWD) carries increased risk of poorer health and quality of life. Non-pharmacological interventions improve outcomes for caregivers of PWDs. We evaluated the efficacy of a modified New York University Caregiver Intervention (NYUCI), named FAMILIES, delivered to spousal and non-spousal caregivers of PWDs from diverse etiologies in a reduced number of sessions.Methods: Participants were 122 primary caregivers for community dwelling PWDs in Virginia. The intervention included two individual and four family/group counseling sessions that integrated dementia education, coping skills and behavioral management training, emotional support, and identification of family and community resources. Assessment of depression, caregiver well-being and burden, and caregiver reactions to the behavioral symptoms of dementia (BSD) were completed at baseline, the sixth session, and 6-month follow-up.Results: Symptoms of depression (p < .001) and caregiver burden (p = .001) and caregivers' capacity to effectively manage their reactions to BSD (p = .003), significantly improved at the sixth session. Benefits were maintained at 6-month follow-up. Being married and female predicted improvement in caregiver burden; being male and living in a rural area predicted reduced risk of depression. Caregivers reported that the intervention was helpful and had a positive impact on the PWD.Conclusions: Modifications to the NYUCI did not diminish its efficacy. Caregivers in FAMILIES experienced improvements in depressive symptoms, caregiver burden, and their ability to effectively manage their reactions to BSD. Systemic support for implementing FAMILIES could have a broad impact on caregivers, PWDs, and the healthcare system.

Lower volume, more impairment: reduced cholinergic basal forebrain grey matter density is associated with impaired cognition in Parkinson disease.

OBJECTIVE: A major contributor to dementia in Parkinson disease (PD) is degeneration of the cholinergic basal forebrain. This study determined whether cholinergic nucleus 4 (Ch4) density is associated with cognition in early and more advanced PD. METHODS: We analysed brain MRIs and neuropsychological test scores for 228 newly diagnosed PD participants from the Parkinson's Progression Markers Initiative (PPMI), 101 healthy controls from the PPMI and 125 more advanced PD patients from a local retrospective cohort. Cholinergic basal forebrain nuclei densities were determined by applying probabilistic maps to MPRAGE T1 sequences processed using voxel-based morphometry methods. Relationships between grey matter densities and cognitive scores were analysed using correlations and linear regression models. RESULTS: In more advanced PD, greater Ch4 density was associated with Montreal Cognitive Assessment (MoCA) score (ß=14.2; 95% CI=1.5 to 27.0; p=0.03), attention domain z-score (ß=3.2; 95% CI=0.8 to 5.5; p=0.008) and visuospatial domain z-score (ß=7.9; 95% CI=2.0 to 13.8; p=0.009). In the PPMI PD cohort, higher Ch4 was associated with higher scores on MoCA (ß=9.2; 95% CI=1.9 to 16.5; p=0.01), Judgement of Line Orientation (ß=20.4; 95% CI=13.8 to 27.0; p<0.001), Letter Number Sequencing (ß=16.5; 95% CI=9.5 to 23.4; p<0.001) and Symbol Digit Modalities Test (ß=41.8; 95% CI=18.7 to 65.0; p<0.001). These same relationships were observed in 97 PPMI PD participants at 4 years. There were no significant associations between Ch4 density and cognitive outcomes in healthy controls. CONCLUSION: In de novo and more advanced PD, lower Ch4 density is associated with impaired global cognition, attention and visuospatial function.

Selection of Normative Group Affects Rates of Mild Cognitive Impairment in Parkinson's Disease.

OBJECTIVE: The objective of this study was to examine the impact of different methods of standardizing cognitive data in the Parkinson's Progression Marker Initiative. METHODS: Cognitive data from 423 participants with Parkinson's disease were included (age = 61.7 [9.7], education = 15.6 [3.0]). Internal norms were calculated using the group mean and standard deviation of the healthy control group. Published norms were compared to the overall group mean of and to age-stratified norms from healthy controls for each neuropsychological test over 4 visits. Rates of mild cognitive impairment were calculated using established criteria. RESULTS: The use of internal norms resulted in lower standardized scores than published norms on all tests with the exception of memory and processing speed (P ≤ .001). Individuals were 1.5 to 2.1 times more likely to be diagnosed with mild cognitive impairment using internal norms than published norms. CONCLUSIONS: Standardization approaches with cognitive data are not interchangeable. Selection of a normative comparison group impacts research and clinical interpretations of cognitive data. © 2018 International Parkinson and Movement Disorder Society.

Subjective Memory Change, Mood, and Cerebrovascular Risk Factors in Older African Americans.

OBJECTIVE: Subjective memory change (SMC) in older individuals may represent a harbinger of cognitive decline. This study examined the factors associated with SMC in older African Americans (AA), who have greater risk of developing dementia. We predicted that symptoms of depression and anxiety, as well as the total number of cerebrovascular risk factors (tCVRFs), but not performances on objective memory measures, would be positively associated with SMC. METHODS: Ninety-six AA completed brief cognitive testing and answered questions about mood and memory at their primary care appointment. Vascular data were obtained from medical records. RESULTS: Symptoms of depression and anxiety, but not performances on objective memory measures, were positively associated with SMC, t(χ2(1) = 16.55 and 12.94, respectively, both P < .001). In nondepressed participants, the tCVRF was important in distinguishing between those with and without SMC. CONCLUSIONS: In older AA, symptoms of depression or anxiety were associated with SMC. In nondepressed AA, the tCVRFs were important in distinguishing between those with and without SMC.

Diagnostic Accuracy and Confidence in the Clinical Detection of Cognitive Impairment in Early-Stage Parkinson Disease.

BACKGROUND/AIMS: Mild cognitive impairment (MCI) is present in up to 34% of patients with early-stage Parkinson disease (PD); however, it is difficult to detect subtle impairment without objective cognitive testing. METHODS: Data were obtained from the Parkinson Progression Marker Initiative. All 341 participants were administered the Montreal Cognitive Assessment (MoCA) and a brief neuropsychological battery. Participants were classified as PD-MCI if MoCA was <26 or if they scored ≥1 standard deviation below the normative mean in 2 or more domains, based upon established criteria. The sensitivity/specificity for the clinical detection of PD-MCI was determined. RESULTS: Overall accuracy for clinical detection of PD-MCI was 67.4%. Although clinical determination was highly specific (96.3%; 95% confidence interval [CI]: 0.92-0.98), sensitivity was poor (32.0%; 95% CI: 0.25-0.40). CONCLUSION: Identifying MCI in early-stage PD based on clinical interview alone appears to be insufficient. The inclusion of objective cognitive tests allowing for normative sample comparisons is needed to increase the detection of cognitive impairment in this population.

Differential susceptibility to motor impulsivity among functional subtypes of Parkinson's disease.

BACKGROUND AND OBJECTIVES: Parkinson's disease patients with predominant postural instability and gait difficulties (PIGD) may experience unique cognitive difficulties compared to patients with tremor predominant (TD) symptoms. PIGD patients are also at high risk for falling, and some of the worst fallers seem to react impulsively to their environment. We tested the hypothesis that PIGD patients show poorer control over motor impulses compared to TD patients. METHODS: 34 PD participants were divided into predominant PIGD (n=17) or TD (n=17) functional subtypes based on their presenting symptoms in their optimally treated motor state. All participants performed a speeded reaction task that quantified motor impulsivity and the proficiency of inhibiting prepotent motor impulses. RESULTS: The groups showed similar reaction times, but compared to TD patients, PIGD patients made significantly more impulsive motor errors. Notably, when the initial impulsive erroneous response was avoided, PIGD and TD groups were similar in their ability to suppress the incorrect motor impulse from further interfering with the selection of a correct action. CONCLUSIONS: PD patients with PIGD predominant symptoms show greater susceptibility to acting on prepotent motor impulses compared to TD patients. This finding may have direct implications for fall risk and also points to dissociable neurocognitive pathologies in TD and PIGD subtypes. Clinically, the use of specific cognitive instruments to assess the expression and inhibition of motor impulses may help identify PD patients who have difficulty 'thinking before they leap' and are at high risk of falling.

Increased glucose concentration in the hippocampus in early Alzheimer's disease following oral glucose ingestion.

Glucose is the primary source of energy for brain cells. Because energy storage in the brain is limited, an uninterrupted supply of glucose and its rapid metabolism are essential for normal cognitive function. This study utilized an oral glucose load to examine hippocampal glucose metabolism in early Alzheimer's disease (AD) - a disease characterized by progressive deterioration of cognitive function and glucose hypometabolism. Short echo time 1H MR spectra (20 ms) from the right hippocampus of 8 patients with probable AD, 14 healthy elderly and 14 healthy young adults were compared pre- and post-glucose loading. In contrast to the healthy adults, the AD patients exhibited significantly elevated hippocampal glucose concentrations post-glucose ingestion relative to baseline (P < .01). These results suggest that cerebral glucose hypometabolism in AD leads to an increased steady-state concentration of cerebral glucose. This research demonstrates the feasibility of studying cerebral glucose metabolism in AD with 1H MR spectroscopy.

Shortening of hippocampal spin-spin relaxation time in probable Alzheimer's disease: a 1H magnetic resonance spectroscopy study.

We quantified the differential effects of the spin-spin relaxation times (T2) of tissue water and cerebral spinal fluid in order to examine hippocampal T2 changes as a non-invasive bio-marker of Alzheimer's disease (AD). We measured T2 in the right hippocampus of ten patients fulfilling the NINCDS-ADRDA criteria for AD and 40 healthy adult volunteers using localized proton magnetic resonance spectroscopy. The T2 values of AD patients (73 +/- 8 ms) were significantly shorter (P < 0.01) than those of healthy age-matched controls (81 +/- 5 ms), and there was a reduction in T2 for healthy older vs. healthy younger adults (87 +/- 5 ms, P < 0.05). The reduced T2 values with aging are consistent with age-related decreases in tissue water content. Our results suggest that there may be a severe reduction in tissue water content in AD.

The use of flight progress strips while working live traffic: frequencies, importance, and perceived benefits.

The Federal Aviation Administration's effort to automate air traffic control (ATC) requires that the functionality provided today be captured in future systems. We report the first quantitative naturalistic observation of paper flight progress strip interactions during operational use. Strip use was similar in a variety of situations, but some uses varied as a function of altitude, staffing, or the cooperative style used by controller teams. Design of automation should proceed by prioritizing changes based on frequency of use and importance and should ensure that an effective method of interacting with flight information is incorporated. In addition to applied relevance to the ATC domain, the results touch on several theoretical concerns relevant to dynamic environments. Actual and potential applications of this research include the establishment of a database of strip activity and an arsenal of information valuable to system designers.

Molality as a unit of measure for expressing 1H MRS brain metabolite concentrations in vivo.

Absolute concentrations of cerebral metabolite in in vivo 1H magnetic resonance spectroscopy studies (1H-MRS) are widely reported in molar units as moles per liter of tissue, or in molal units as moles per kilogram of tissue. Such measurements require external referencing or assumptions as to local water content. To reduce the scan time, avoid assumptions that may be invalid under specific pathologies, and provide a universally accessible referencing procedure, we suggest that metabolite concentrations from 1H-MRS measurements in vivo be reported in molal units as moles per kilogram of tissue water. Using internal water referencing, a two-compartment water model, a simulated brain spectrum for peak identification, and a spectroscopic bi-exponential spin-spin relaxation segmentation technique, we measured the absolute concentrations for the four common 1H brain metabolites: choline (Cho), myo-inositol (mIno), phosphocreatine + creatine (Cr), and N-acetyl-aspartate (NAA), in the hippocampal region (n = 26) and along the Sylvian fissure (n = 61) of 35 healthy adults. A stimulated echo localization method (20 ms echo time, 10 ms mixing time, 4 s repetition time) yielded metabolite concentrations, uncorrected for metabolite relaxation or contributions from macromolecule resonances, that were expectantly higher than with molar literature values. Along the Sylvian fissure the average concentrations (coefficient of variation (CV)) in mmoles/kg of tissue water were 17.6 (12%) for NAA, 14.2 (9%) for Cr, 3.6 (13%) for Cho, and 13.2 (15%) for mIno. Respective values for the hippocampal region were 15.7 (20%), 14.7 (16%), 4.6 (19%), and 17.7 (26%). The concentrations of the two regions were significantly different (p

Constrained modeling for spectroscopic measurement of bi-exponential spin-lattice relaxation of water in vivo.

The (1)H NMR water signal from spectroscopic voxels localized in gray matter contains contributions from tissue and cerebral spinal fluid (CSF). A typically weak CSF signal at short echo times makes separating the tissue and CSF spin-lattice relaxation times (T(1)) difficult, often yielding poor precision in a bi-exponential relaxation model. Simulations show that reducing the variables in the T(1) model by using known signal intensity values significantly improves the precision of the T(1) measurement. The method was validated on studies on eight healthy subjects (four males and four females, mean age 21 +/- 2 years) through a total of twenty-four spectroscopic relaxation studies. Each study included both T(1) and spin-spin relaxation (T(2)) experiments. All volumes were localized along the Sylvian fissure using a stimulated echo localization technique with a mixing time of 10 ms. The T(2) experiment consisted of 16 stimulated echo acquisitions ranging from a minimum echo time (TE) of 20 ms to a maximum of 1000 ms, with a repetition time of 12 s. All T(1) experiments consisted of 16 stimulated echo acquisition, using a homospoil saturation recovery technique with a minimum recovery time of 50 ms and a maximum 12 s. The results of the T(2) measurements provided the signal intensity values used in the bi-exponential T(1) model. The mean T(1) values when the signal intensities were constrained by the T(2) results were 1055.4 ms +/- 7.4% for tissue and 5393.5 ms +/- 59% for CSF. When the signal intensities remained free variables in the model, the mean T(1) values were 1085 ms +/- 19.4% and 5038.8 ms +/- 113.0% for tissue and CSF, respectively. The resulting improvement in precision allows the water tissue T(1) value to be included in the spectroscopic characterization of brain tissue.