Diagnostic Utility of Hippocampal Volumetric Data in a Memory Disorder Clinic Setting.

BACKGROUND: Hippocampal volumetric data are widely used in research but are rarely examined in clinical populations in regard to aiding diagnosis or correlating with objective memory test scores. OBJECTIVE: To replicate and expand on the few prior clinical examinations of the utility of hippocampal volumetric data. We evaluated MRI volumetric data to determine (a) the degree of hippocampal loss across diagnostic groups compared with a cognitively intact group, (b) if total or lateralized hippocampal volumes predict diagnostic group membership, and (c) how total and lateralized volumes correlate with memory tests. METHOD: We retrospectively examined hippocampal volumetric data and memory test scores for 294 individuals referred to a memory clinic. RESULTS: Individuals with mild cognitive impairment or Alzheimer disease had smaller hippocampal volumes compared with cognitively intact individuals. The raw and normalized total and lateralized hippocampal volumes were essentially equal for predicting diagnostic group membership, and notably low hippocampal volumes evidenced greater specificity than sensitivity. All of the volumetric data correlated with the memory test scores, with the total and left hippocampal volumes accounting for the slightly more variance in the diagnostic groups. CONCLUSION: The diagnostic groups exhibited hippocampal volume loss, which can be a potential biomarker for neurodegenerative disease in clinical practice. However, solely using hippocampal volumetric data to predict diagnostic group membership or memory test failure was not supported. While extreme hippocampal volume loss was rare in the cognitively intact group, the sensitivity of these volumetric data suggests a need for supplementation by other tools when making a diagnosis.

COVID-19 associated parotitis.

As the 2019 coronavirus pandemic has unfolded, an increasing number of atypical presentations of COVID-19 have been reported. As patients with COVID-19 often present to emergency departments for initial care, it is important that emergency clinicians are familiar with these atypical presentations in order to prevent disease transmission. We present a case of a 21-year-old woman diagnosed in our ED with COVID-19 associated parotitis and review the epidemiology and management of parotitis. We discuss the importance of considering COVID-19 in the differential of parotitis and other viral-associated syndromes and emphasize the importance of donning personal protective equipment during the initial evaluation.

Chronic Use of Aspirin and Total White Matter Lesion Volume: Results from the Women's Health Initiative Memory Study of Magnetic Resonance Imaging Study.

OBJECTIVE: To investigate the relationship between aspirin and subclinical cerebrovascular heath, we evaluated the effect of chronic aspirin use on white matter lesions (WML) volume among women. METHODS: Chronic aspirin use was assessed in 1365 women who participated in the Women's Health Initiative Memory Study of Magnetic Resonance Imaging. Differences in WML volumes between aspirin users and nonusers were assessed with linear mixed models. A number of secondary analyses were performed, including lobe-specific analyses, subgroup analyses based on participants' overall risk of cerebrovascular disease, and a dose-response relationship analysis. RESULTS: The mean age of the women at magnetic resonance imaging examination was 77.6 years. Sixty-one percent of participants were chronic aspirin users. After adjusting for demographic variables and comorbidities, chronic aspirin use was nonsignificantly associated with 4.8% (95% CI: -6.8%, 17.9%) larger WML volumes. These null findings were confirmed in secondary and sensitivity analyses, including an active comparator evaluation where aspirin users were compared to users of nonaspirin nonsteroidal anti-inflammatory drugs or acetaminophen. CONCLUSIONS: There was a nonsignificant difference in WML volumes between aspirin users and nonusers. Further, our results suggest that chronic aspirin use may not have a clinically significant effect on WML volumes in women.

Datafish Multiphase Data Mining Technique to Match Multiple Mutually Inclusive Independent Variables in Large PACS Databases.

Retrospective data mining has tremendous potential in research but is time and labor intensive. Current data mining software contains many advanced search features but is limited in its ability to identify patients who meet multiple complex independent search criteria. Simple keyword and Boolean search techniques are ineffective when more complex searches are required, or when a search for multiple mutually inclusive variables becomes important. This is particularly true when trying to identify patients with a set of specific radiologic findings or proximity in time across multiple different imaging modalities. Another challenge that arises in retrospective data mining is that much variation still exists in how image findings are described in radiology reports. We present an algorithmic approach to solve this problem and describe a specific use case scenario in which we applied our technique to a real-world data set in order to identify patients who matched several independent variables in our institution's picture archiving and communication systems (PACS) database.

Performance of the NINDS-CSN 5-minute protocol in a national population-based sample.

In 2006, the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) Vascular Cognitive Impairment Harmonization Standards recommended a 5-Minute Protocol as a brief screening instrument for vascular cognitive impairment (VCI). We report demographically adjusted norms for the 5-Minute Protocol and its relation to other measures of cognitive function and cerebrovascular risk factors. We performed a cross-sectional analysis of 7199 stroke-free adults in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study on the NINDS-CSN 5-Minute Protocol score. Total scores on the 5-Minute Protocol were inversely correlated with age and positively correlated with years of education, and performance on the Six-Item Screener, Word List Learning, and Animal Fluency (all p-values <.001). Higher cerebrovascular risk on the Framingham Stroke Risk Profile (FSRP) was associated with lower total 5-Minute Protocol scores (p <.001). The 5-Minute Protocol also differentiated between participants with and without confirmed stroke and with and without stroke symptom histories (p <.001). The NINDS-CSN 5-Minute Protocol is a brief, easily administered screening measure that is sensitive to cerebrovascular risk and offers a valid method of screening for cognitive impairment in populations at risk for VCI.

Beyond the Wizard of Oz: Negative Effects of Imperfect Machine Learning to Examine the Impact of Reliability of Augmented Reality Cues on Visual Search Performance.

Despite knowing exactly what an object looks like, searching for it in a person's visual field is a time-consuming and error-prone experience. In Augmented Reality systems, new algorithms are proposed to speed up search time and reduce human errors. However, these algorithms might not always provide 100% accurate visual cues, which might affect users' perceived reliability of the algorithm and, thus, search performance. Here, we examined the detrimental effects of automation bias caused by imperfect cues presented in the Augmented Reality head-mounted display using the YOLOv5 machine learning model. 53 participants in the two groups received either 100% accurate visual cues or 88.9% accurate visual cues. Their performance was compared with the control condition, which did not include any additional cues. The results show how cueing may increase performance and shorten search times. The results also showed that performance with imperfect automation was much worse than perfect automation and that, consistent with automation bias, participants were frequently enticed by incorrect cues.

Preventing cognitive decline by reducing BP target (PCOT): A randomized, pragmatic, multi-health systems clinical trial.

BACKGROUND: Growing evidence suggests that intensive lowering of systolic blood pressure (BP) may prevent mild cognitive impairment (MCI) and dementia. However, current guidelines provide inconsistent recommendations regarding optimal BP targets, citing safety concerns of excessive BP lowering in the diverse population of older adults. We are conducting a pragmatic trial to determine if an implementation strategy to reduce systolic BP to <130 and diastolic BP to <80 mmHg will safely slow cognitive decline in older adults with hypertension when compared to patients receiving usual care. METHODS: The Preventing Cognitive Decline by Reducing BP Target Trial (PCOT) is an embedded randomized pragmatic clinical trial in 4000 patients from two diverse health-systems who are age ≥ 70 years with BP >130/80 mmHg. Participants are randomized to the intervention arm or usual care using a permuted block randomization within each health system. The intervention is a combination of team-based care with clinical decision support to lower home BP to <130/80 mmHg. The primary outcome is cognitive decline as determined by the change in the modified Telephone Interview for Cognitive Status (TICS-m) scores from baseline. As a secondary outcome, patients who decline ≥3 points on the TICS-m will complete additional cognitive assessments and this information will be reviewed by an expert panel to determine if they meet criteria for MCI or dementia. CONCLUSION: The PCOT trial will address the effectiveness and safety of hypertension treatment in two large health systems to lower BP targets to reduce risk of cognitive decline in real-world settings.

Using RBANS to characterize cognitive treatment response in autoimmune encephalopathy.

INTRODUCTION: Autoimmune encephalopathy (AE) is an increasingly recognized cause of cognitive impairment. This study investigates the use of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to characterize treatment response of AE cognitive symptoms in ambulatory clinical practice. METHODS: Retrospective evaluation of 29 consecutive patients treated for AE at the University of Cincinnati Memory Disorders Clinic. All patients underwent RBANS before treatment and 4-5 weeks after treatment. The Reliable Change index and clinically meaningful improvement method were used to determine if changes in RBANS performance were clinically significant. RESULTS: Clinically meaningful improvement was seen in 20 out of 29 (69 %) subjects on one or more RBANS domains and in 13 patients (45 %) for the global RBANS index. Measured improvement on one or more cognitive domain scores showed excellent agreement with clinical impression of change. CONCLUSION: The RBANS provided an efficient and effective means to document cognitive outcomes and treatment response in AE. The brief administration time, availability of normative data, and alternate versions make the RBANS useful in clinical practice and in clinical research related to AE.

Linking Problems Reported by Care Partners of Individuals With Alzheimer's Disease and Lewy Body Dementia to the International Classification of Functioning Disability and Health.

Aim: This study aims to classify, describe, and compare the problems reported by care partners of adults with Alzheimer's disease (AD) and Lewy body dementia (LBD) using the International Classification of Functioning Disability and Health (ICF). Methods: Problems that care partners experience were collected during a problem-solving training intervention. The meaningful concepts were then extracted and linked to the ICF using a standardized linking technique. Results: 402 meaningful concepts were extracted from 128 problems reported by care partners. 79.4% of the concepts were linkable to the ICF. "Body functions" was most frequently addressed followed by "Activities and participation." LBD care partners reported more problems (M = 23.6 ± 13.4) on average than AD care partners (M = 19.4 ± 12.1). LBD care partners reported greater relative proportions of problems in mental function (emotional and sleep functions) than AD care partners. Conclusion: This study suggests that the experience of LBD care partners may include significantly more challenges and may be more emotionally demanding than the care experience of AD care partners. Interventions designed to support care partners of adults with dementia may need to be tailored to meet the needs of care partners based on the care receiver's type of dementia.

Comparing the effects of bisphenol A, C, and F on bovine theca cells in vitro.

Endocrine disrupting chemicals (EDCs) target aspects of hormone activity. Tightly coordinated crosstalk between two somatic cells of the ovary, granulosa and theca cells, governs steroid hormone production and plays a critical role in reproduction. It is thus pertinent to understand the impact of EDCs on granulosa and theca cells. Bisphenol A (BPA), a well-known EDC, is widely used in the manufacturing of consumer products with humans routinely exposed. Strong evidence of the adverse effects of BPA on the female reproductive system has emerged and as a result, manufacturers have begun replacing BPA with other bisphenols, such as BPC and BPF. The safety of these analogs is currently unclear and should be investigated independently. Although much is known about the impact of BPA on granulosa cells, similar study of theca cells has been neglected. Further, there is a lack of studies on the impact of BPC and BPF on the female reproductive system. To fill these gaps, the present study compared the effect of BPA, BPC, and BPF on the viability and steroid production of theca cells from bovine, a clinically relevant model for human reproduction. We show that BPC is more detrimental to theca cell viability and progesterone production compared to BPA. Surprisingly, we also found that BPF induces an increase in progesterone production compared to a decrease with BPA and BPC. To determine safety for the reproductive system, we conclude that a major shift away from BPA to bisphenol analogs should be investigated more thoroughly.

Cognitive Decline in Older People with Multiple Sclerosis-A Narrative Review of the Literature.

Several important questions regarding cognitive aging and dementia in older people with multiple sclerosis (PwMS) are the focus of this narrative review: Do older PwMS have worse cognitive decline compared to older people without MS? Can older PwMS develop dementia or other neurodegenerative diseases such as Alzheimer's disease (AD) that may be accelerated due to MS? Are there any potential biomarkers that can help to determine the etiology of cognitive decline in older PwMS? What are the neural and cellular bases of cognitive aging and neurodegeneration in MS? Current evidence suggests that cognitive impairment in MS is distinguishable from that due to other neurodegenerative diseases, although older PwMS may present with accelerated cognitive decline. While dementia is prevalent in PwMS, there is currently no consensus on defining it. Cerebrospinal fluid and imaging biomarkers have the potential to identify disease processes linked to MS and other comorbidities-such as AD and vascular disease-in older PwMS, although more research is required. In conclusion, one should be aware that multiple underlying pathologies can coexist in older PwMS and cause cognitive decline. Future basic and clinical research will need to consider these complex factors to better understand the underlying pathophysiology, and to improve diagnostic accuracy.

Mild Traumatic Brain Injury Is Related to Elevated Cerebrospinal Fluid Tau in Alzheimer's Disease Dementia.

Few studies have examined an association between mild traumatic brain injury (mTBI) and Alzheimer's disease (AD). For this reason, we compared an AD dementia group with an mTBI history (n = 10) to a matched AD control group (n = 20) on measures of cognitive function, cerebral glucose metabolism, and markers of amyloid and tau deposition. Only a trend and medium-to-large effect size for higher phosphorylated and total tau was identified for the mTBI group. A history of mTBI may be associated with greater tau in AD, indicating a potential pathway for increasing risk for AD, though further evaluation with larger samples is needed.

CSF-Derived CD4+ T-Cell Diversity Is Reduced in Patients With Alzheimer Clinical Syndrome.

BACKGROUND AND OBJECTIVES: Patients with Alzheimer dementia display evidence of amyloid-related neurodegeneration. Our focus was to determine whether such patients also display evidence of a disease-targeting adaptive immune response mediated by CD4+ T cells. To test this hypothesis, we evaluated the CSF immune profiles of patients with Alzheimer clinical syndrome (ACS), who display clinically defined dementia. METHODS: Innate and adaptive immune profiles of patients with ACS were measured using multicolor flow cytometry. CSF-derived CD4+ and CD8+ T-cell receptor repertoire genetics were measured using next-generation sequencing. Brain-specific autoantibody signatures of CSF-derived antibody pools were measured using array technology or ELISA. CSF from similar-age healthy controls (HCs) was used as a comparator cohort. RESULTS: Innate cells were expanded in the CSF of patients with ACS in comparison to HCs, and innate cell expansion increased with age in the patients with ACS, but not HCs. Despite innate cell expansion in the CSF, the frequency of total CD4+ T cells reduced with age in the patients with ACS. T-cell receptor repertoire genetics indicated that T-cell clonal expansion is enhanced, and diversity is reduced in the patients with ACS compared with similar-age HCs. DISCUSSION: Examination of CSF indicates that CD4+ T cell-mediated adaptive immune responses are altered in patients with ACS. Understanding the underlying mechanisms affecting adaptive immunity will help move us toward the goal of slowing cognitive decline.

A secreted effector protein (SNE1) from Phytophthora infestans is a broadly acting suppressor of programmed cell death.

Evasion or active suppression of host defenses are critical strategies employed by biotrophic phytopathogens and hemibiotrophs whose infection mechanism includes sequential biotrophic and necrotrophic stages. Although defense suppression by secreted effector proteins has been well studied in bacteria, equivalent systems in fungi and oomycetes are poorly understood. We report the characterization of SNE1 (suppressor of necrosis 1), a gene encoding a secreted protein from the hemibiotrophic oomycete Phytophthora infestans that is specifically expressed at the transcriptional level during biotrophic growth within the host plant tomato (Solanum lycopersicum). Using transient expression assays, we show that SNE1 suppresses the action of secreted cell death-inducing effectors from Phytophthora that are expressed during the necrotrophic growth phase, as well as programmed cell death mediated by a range of Avr-R protein interactions. We also report that SNE1 contains predicted NLS motifs and translocates to the plant nucleus in transient expression studies. A conceptual model is presented in which the sequential coordinated secretion of antagonistic effectors by P. infestans first suppresses, but then induces, host cell death, thereby providing a highly regulated means to control the transition from biotrophy to necrotrophy.

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis.

Spirituality in Primary Palliative Care and Beyond: A 20-Year Longitudinal Qualitative Study of Interacting Factors Impacting Physicians' Spiritual Care Provision Over Time.

CONTEXT: Spiritual care (SC) is central to palliative care. However, a mismatch between patients' desire for SC and physicians' SC provision remains. The shortage of specialty-trained palliative physicians, necessitates that all physicians provide primary palliative care, including SC. Although several quantitative studies explore physicians' barriers to SC, few qualitative studies and no longitudinal studies exist. OBJECTIVE: To gain in-depth understanding of factors influencing physicians' ability to provide SC over time. METHODS: A 20-year longitudinal, individual interview study. In study year-1, we interviewed all residents in a USA primary care residency (full study-group) regarding SC beliefs, experiences and skills. The longitudinal study-group (PGY1 subgroup) was interviewed again in study-years 3, 11, and 20. Interviews were audio-recorded and transcribed. Four researchers analyzed transcripts using a grounded theory approach. IRB approval was obtained. RESULTS: We analyzed 66 interviews from 34 physicians. Physicians had diverse personal spiritual beliefs. Seven themes emerged from both groups (response rate 89%): patients' needs; practice setting; beliefs regarding physician's role; personal spiritual beliefs; SC training; life experiences (professional, personal); self-care and reflection. Longitudinal interviews revealed thematic evolution and interactions over 20-years: patients' needs and physicians' belief in whole-person care remained primary motivators; cross-cultural SC communication training diminished impact of personal spiritual beliefs and worries; life experiences enhanced SC skills; work environment helped or hindered SC provision; and spiritual self-care/reflection fostered patient-centered, compassionate SC. CONCLUSION: Facilitating SC provision by nonpalliative care specialists is complex and may require both individual and systems level interventions fostering motivation, SC skill development, and supportive work environments.

Bilingual problem-solving training for caregivers of adults with dementia: A randomized, factorial-design protocol for the CaDeS trial.

OBJECTIVE: Caregivers of individuals with Alzheimer's disease and related dementias (ADRD) often experience debilitating caregiver burden and emotional distress. To address these negative emotional consequences of caregiving, we will test and refine a strategy training intervention - Problem-Solving Training (PST) - that promotes self-efficacy and reduces caregiver burden and depressive symptoms. Previous research supports efficacy of PST; however, we do not know exactly how many PST sessions are needed or if post-training "boosters" are required to maintain PST benefits. Additionally, we translated and culturally-adapted PST into "Descubriendo Soluciones Juntos" (DSJ), our novel intervention for Spanish-speaking caregivers. METHOD: In this 2 × 2 factorial design randomized controlled trial, we will test remotely-delivered PST/DSJ sessions for both English- and Spanish-speaking caregivers of persons with ADRD to determine the optimal number of PST/DSJ sessions and ongoing "booster" sessions needed to best help caregivers navigate their current and future needs. AIMS: 1) Compare the efficacy of three vs. six PST/DSJ sessions each with and without booster sessions for decreasing caregiver burden and depression and enhancing caregiver problem-solving; 2) Identify key factors associated with efficacy of PST/DSJ, including age, gender, primary language, relationship to care recipient, and uptake of the PST/DSJ strategy. RESULTS: These results will establish guidelines needed for an evidence-based, culturally-adapted, and implementable problem-solving intervention to reduce caregiver stress and burden and improve caregiver health and well-being. CONCLUSION: This work promotes inclusion of diverse and underserved populations and advances therapeutic behavioral interventions that improve the lives of caregivers of individuals with chronic conditions.

Sonographic Diagnosis of Velamentous and Marginal Placental Cord Insertion.

Routine second trimester ultrasound (US) examinations include an assessment of the umbilical cord given its vital role as a vascular conduit between the maternal placenta and fetus during fetal development. Placental cord insertion abnormalities can be identified during prenatal US screening and are increasingly recognized as independent risk factors for various complications during pregnancy and delivery. The purpose of this pictorial review is to illustrate examples of velamentous and marginal placental cord insertion with an emphasis on how to differentiate their morphology using color Doppler US.

Cognitive and noncognitive neurological features of young-onset dementia.

BACKGROUND: The rarity of young-onset dementia (YOD), the broad differential diagnosis and unusual clinical presentations present unique challenges to correctly recognize the condition and establish an accurate diagnosis. Limited data exist regarding clinical features associated with dementia prior to the age of 45. METHODS: We retrospectively assessed cognitive and noncognitive neurological characteristics of 235 patients who presented for evaluation of YOD to investigate the clinical characteristics of YOD compared to later-onset dementias and to identify clinical features associated with specific etiologies that may aid in the evaluation of YOD. RESULTS: Multiple cognitive domains were affected in most patients, and no significant differences in affected domains existed between groups. Early psychiatric and behavioral features occurred at very high frequencies. Nearly 80% of this YOD cohort had additional noncognitive symptoms or signs as a feature of their disease. Chorea was strongly associated with Huntington disease. Parkinsonism was not seen in patients having an autoimmune/inflammatory etiology. CONCLUSIONS: The rarity of YOD and the high frequency of early psychiatric features led to frequent misdiagnosis early in the clinical course. The high frequency of noncognitive symptoms and signs may aid clinicians in distinguishing patients requiring a more extensive evaluation for YOD.

Rapidly progressive young-onset dementia.

OBJECTIVE: To characterize a cohort of individuals who have experienced rapidly progressive dementia with onset before age 45. BACKGROUND: Very little data regarding the clinical features or clinical spectrum of rapidly progressive young-onset dementia (RP-YOD) is available, primarily consisting of case reports or small series. METHODS: A search of the Mayo Clinic medical record was employed to identify patients who had onset before age 45 of rapidly progressive dementia. All available medical records, laboratory data, neuroimaging studies, and pathologic data were reviewed. RESULTS: Twenty-two patients met the predefined inclusion and exclusion criteria. Behavioral and affective disorders, cerebellar dysfunction, and visual and/or oculomotor dysfunction were common early clinical features within the cohort, as were clinical features often associated with Creutzfeldt-Jakob disease. Diagnostic testing identified an etiology in most patients. CONCLUSIONS: Presentations of RP-YOD result from a variety of etiologies and significant overlap in clinical features is observed. Clinical features often associated with Creutzfeldt-Jakob disease seem to be common within the entire cohort of RP-YOD patients. Diagnostic studies aided in establishing a diagnosis in most patients, however 5 had uncertain diagnoses despite exhaustive evaluation.