The Relationship Between First Presenting Neuropsychiatric Symptoms in Older Adults and Autopsy-Confirmed Memory Disorders.

OBJECTIVES: Although dementia is typically considered a disease of cognitive decline, almost all patients present with neuropsychiatric symptoms (NPS) at some stage of their disease. Few studies have assessed the timing of NPS onset in relation to pathological diagnoses of neurodegenerative diseases. We sought to examine the association between the first presenting clinically significant NPS in aging individuals and neuropathological diagnoses of memory disorders. DESIGN: This retrospective longitudinal cohort study utilized the National Alzheimer's Coordinating Center (NACC) dataset, which includes participant data from 37 Alzheimer's Disease Research Centers collected between 2005 and 2022. PARTICIPANTS: Participants (N = 5,416) aged 45 years or older with Clinical Dementia Rating-Global ratings of less than or equal to 1 were included in this analysis. A total of 4,033 (74.5%) participants presented with at least one NPS at any NACC visit. MEASUREMENTS: To measure first NPS, the NACCBEHF variable was used, a clinician-rated variable defined as "the predominant symptom that was first recognized as a decline in the subject's behavior." Neuropathologic variables included assessments of Alzheimer's Disease, Frontotemporal Dementia, Lewy Body Dementia, Cerebral Amyloid Angiopathy, Hippocampal Sclerosis, and Cerebrovascular Disease. RESULTS: Presentation with any clinically significant first NPS was associated with several neuropathological diagnoses including Alzheimer's Disease, Frontotemporal Lobar Dementia with TDP-43 pathology, and Lewy Body Dementia. While specific first NPS were associated with Frontotemporal Dementia neuropathology (personality change and disinhibition) and Lewy Body Dementia neuropathology (psychosis and REM behavior disturbance), Alzheimer's Disease neuropathology was associated with the majority of NPS. CONCLUSIONS: Since neuropsychiatric symptoms are frequently the first presenting symptom of dementia, their associations with well-defined neuropathological diagnoses may help clinicians predict the subtype of future dementias.

A Longitudinal Study of COVID-19 Sequelae and Immunity: Baseline Findings.

BACKGROUND: A substantial proportion of persons who develop COVID-19 report persistent symptoms after acute illness. Various pathophysiologic mechanisms have been implicated in the pathogenesis of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To characterize medical sequelae and persistent symptoms after recovery from COVID-19 in a cohort of disease survivors and controls. DESIGN: Cohort study. (ClinicalTrials.gov: NCT04411147). SETTING: National Institutes of Health Clinical Center, Bethesda, Maryland. PARTICIPANTS: Self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of PASC. A control group comprised persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, recruited regardless of their current health status. Both groups were enrolled over the same period and from the same geographic area. MEASUREMENTS: All participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset also underwent exploratory immunologic and virologic evaluations. RESULTS: 189 persons with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC. LIMITATIONS: Most participants with COVID-19 had mild to moderate acute illness that did not require hospitalization. The prevalence of reported PASC was likely overestimated in this cohort because persons with PASC may have been more motivated to enroll. The study did not capture PASC that resolved before enrollment. CONCLUSION: A high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19. PRIMARY FUNDING SOURCE: Division of Intramural Research, National Institute of Allergy and Infectious Diseases.

Toward Personalized Cognitive Training in Older Adults: A Pilot Investigation of the Effects of Baseline Performance and Age on Cognitive Training Outcomes.

BACKGROUND: Cognitive training holds potential as a non-pharmacological intervention to decrease cognitive symptoms associated with Alzheimer's disease (AD), but more research is needed to understand individual differences that may predict maximal training benefits. OBJECTIVE: We conducted a pilot study using a six-month training regimen in healthy aging adults with no cognitive decline. We investigated the effects of baseline performance and age on training and transfer improvements. METHODS: Out of 43 participants aged 65-84 years, 31 successfully completed cognitive training (BrainHQ) in one of three cognitive domains: processing speed (N = 13), inhibitory control (N = 9), or episodic memory (N = 9). We used standardized assessments to measure baseline performance and transfer effects. RESULTS: All 31 participants improved on the cognitive training regimen and age was positively associated with training improvement (p = 0.039). The processing speed group improved significantly across many near- and far-transfer tasks. In the inhibitory control group, individuals with lower baseline performance improved more on inhibitory control and cognitive flexibility tasks. In the episodic memory group, older individuals improved most on a memory task while younger individuals improved most on an executive function far-transfer task. CONCLUSIONS: Individual differences are predictive of cognitive training gains, and the impact of individual differences on training improvements is specific to the domain of training. We provide initial insight regarding how non-pharmacological interventions can be optimized to combat the onset of cognitive decline in older adults. With future research this work can inform the design of effective cognitive interventions for delaying cognitive decline in preclinical AD.

Pandemic-Related Post-traumatic Stress Symptomatology in COVID-19 Patients with and without Post-COVID Conditions.

Trauma and stressor-related symptoms have been frequently reported during the COVID-19 pandemic. Few studies compare post-traumatic stress symptoms (PTSS) between patients and non-infected controls. Using data from an ongoing natural history study of COVID-19, this study compared PTSS between patients infected with SARS-CoV-2 during the first year of the pandemic and controls. Within the COVID-19 patient cohort, we also compared PTSS between patients with and without post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 infection (PASC). This study also examined the association of PTSS with trait resilience and prior trauma exposure. PTSS were assessed using the Impact of Event Scaled-Revised (IES-R), which has a validated probable PTSD cutoff (score ≥33). The results showed that patients (n=131) reported significantly higher IES-R scores than controls (n=82) and had significantly higher odds of having scores indicative of PTSD [AOR: 4.17 p: 0.029]. IES-R scores among PASC patients (n=68) were significantly elevated compared to patients without PASC (n=63) and PASC patients did not have higher odds for probable PTSD [AOR: 2.60; p: 0.14]. Trait resilience was associated with lower PTSS. These findings help characterize the mental health impact of the COVID-19 illness experience and highlight elevated PTSS in patients with persistent post-COVID conditions.

Examining the factor structure of the DSM-5 Level 1 cross-cutting symptom measure.

OBJECTIVES: The DSM-5 Level 1 Cross-Cutting Symptom Measure (DSM-XC) was developed by the American Psychiatric Association as a transdiagnostic mental health symptom survey. Despite its promise as a screening tool, few studies have assessed its latent dimensionality or provided guidance on interpreting responses. We examined the factor structure of the DSM-XC in a convenience sample of participants with varying degrees of psychopathology. METHODS: Participants (n = 3533) were enrolled in an online study on the mental health impact of COVID-19 (NCT04339790). We used a factor analytic framework with exploratory and confirmatory analyses to evaluate candidate factor solutions. Convergent validity analysis with concurrent study measures was also performed. RESULTS: Six-factor and bifactor candidate solutions both had good fit and full measurement invariance across age, sex, and enrollment date. The six-factor solution resulted in constructs labeled as: mood, worry, activation, somatic, thought, and substance use. A general psychopathology factor and two residual factors (mood and anxiety constructs) explained the variance of the bifactor solution. CONCLUSIONS: Our analysis supports that the DSM-XC is a multidimensional instrument spanning many mental health symptoms. We provide scoring solutions for two factor structures that capture broader constructs of psychopathology. Use of a convenience sample may limit generalizability of findings.

Trends in Language Use During the COVID-19 Pandemic and Relationship Between Language Use and Mental Health: Text Analysis Based on Free Responses From a Longitudinal Study.

BACKGROUND: The COVID-19 pandemic and its associated restrictions have been a major stressor that has exacerbated mental health worldwide. Qualitative data play a unique role in documenting mental states through both language features and content. Text analysis methods can provide insights into the associations between language use and mental health and reveal relevant themes that emerge organically in open-ended responses. OBJECTIVE: The aim of this web-based longitudinal study on mental health during the early COVID-19 pandemic was to use text analysis methods to analyze free responses to the question, "Is there anything else you would like to tell us that might be important that we did not ask about?" Our goals were to determine whether individuals who responded to the item differed from nonresponders, to determine whether there were associations between language use and psychological status, and to characterize the content of responses and how responses changed over time. METHODS: A total of 3655 individuals enrolled in the study were asked to complete self-reported measures of mental health and COVID-19 pandemic-related questions every 2 weeks for 6 months. Of these 3655 participants, 2497 (68.32%) provided at least 1 free response (9741 total responses). We used various text analysis methods to measure the links between language use and mental health and to characterize response themes over the first year of the pandemic. RESULTS: Response likelihood was influenced by demographic factors and health status: those who were male, Asian, Black, or Hispanic were less likely to respond, and the odds of responding increased with age and education as well as with a history of physical health conditions. Although mental health treatment history did not influence the overall likelihood of responding, it was associated with more negative sentiment, negative word use, and higher use of first-person singular pronouns. Responses were dynamically influenced by psychological status such that distress and loneliness were positively associated with an individual's likelihood to respond at a given time point and were associated with more negativity. Finally, the responses were negative in valence overall and exhibited fluctuations linked with external events. The responses covered a variety of topics, with the most common being mental health and emotion, social or physical distancing, and policy and government. CONCLUSIONS: Our results identify trends in language use during the first year of the pandemic and suggest that both the content of responses and overall sentiments are linked to mental health.

The Emotional and Personal Experiences of the COVID-19 Illness During the Early Pandemic: A Qualitative Study.

BACKGROUND: Several studies report the incidence of psychiatric symptoms and disorders among patients who recovered from coronavirus disease 2019 (COVID-19); however, little is known about the emotional impact of acute COVID-19 illness and recovery on these survivors. Qualitative methods are ideal for understanding the psychological impact of a novel illness. OBJECTIVE: To describe the emotional experience of the acute COVID-19 illness and recovery in patients who contracted the virus during the early months of the pandemic. METHODS: Semi-structured interviews conducted by consultation-liaison (C-L) psychiatrists were used to elicit participant responses about the emotional impact of the acute and recovery phases of the COVID-19 illness. Participants recruited from the Maryland, District of Columbia, and Virginia area were interviewed which was audio recorded between June 2020 and December 2020. The research team extracted qualitative themes from the recordings using the principles of thematic analysis. RESULTS: One hundred and one COVID-19 survivors (54 women; mean [SD] age, 50 [14.7] years) were interviewed at a mean of 5.16 months after their acute illness, and their responses were audio-recorded. Most participants were White (77%), non-Hispanic/Latino (86.1%), and not hospitalized for COVID-19 (87.1%). Coders identified 26 themes from participant responses. The most frequently coded themes included anxiety/worry (49), uncertainty (37), supportfrom others (35), alone/isolation (32), and positive reframe/positive emotions (32). CONCLUSIONS: Survivors who contracted severe acute respiratory syndrome coronavirus 2 during the early months of the pandemic described both negative and positive valence emotions. They experienced emotional distress and psychosocial stressors associated with the acute illness and recovery but also drew upon personal resiliency to cope. This report highlights the utility of qualitative research methods in identifying emotional responses to a novel illness that may otherwise go unnoted. Consultation-liaison psychiatrists may be uniquely positioned to work in collaboration with medical colleagues in developing a multidimensional approach to evaluating an emerging illness.

The NIMH intramural healthy volunteer dataset: A comprehensive MEG, MRI, and behavioral resource.

The NIMH Healthy Research Volunteer Dataset is a collection of phenotypic data characterizing healthy research volunteers using clinical assessments such as assays of blood and urine, mental health assessments, diagnostic and dimensional measures of mental health, cognitive and neuropsychological functioning, structural and functional magnetic resonance imaging (MRI), along with diffusion tensor imaging (DTI), and a comprehensive magnetoencephalography battery (MEG). In addition, blood samples of healthy volunteers are banked for future analyses. All data collected in this protocol are broadly shared in the OpenNeuro repository, in the Brain Imaging Data Structure (BIDS) format. In addition, task paradigms and basic pre-processing scripts are shared on GitHub. There are currently few open access MEG datasets, and multimodal neuroimaging datasets are even more rare. Due to its depth of characterization of a healthy population in terms of brain health, this dataset may contribute to a wide array of secondary investigations of non-clinical and clinical research questions.

Examining the Factor Structure of the DSM-5 Level 1 Cross-Cutting Symptom Measure.

OBJECTIVES: The DSM-5 Level 1 Cross-Cutting Symptom Measure (DSM-XC) is a transdiagnostic mental health symptom measure that has shown promise in informing clinical diagnostic evaluations and as a screening tool for research. However, few studies have assessed the latent dimensionality of the DSM-XC. We examined the factor structure of the DSM-XC in a large convenience sample of participants with varying degrees of psychological health. METHODS: Participants (n=3533) enrolled in a protocol conducted at the National Institute of Mental Health (NCT04339790). We used a factor analytic framework to evaluate an existing two-factor solution (Lace & Merz, 2020) and two additional candidate solutions. RESULTS: The Lace and Merz solution had acceptable fit. Exploratory factor analysis yielded two candidate solutions: a six-factor (characterized as mood, worry, activation, somatic, thoughts, and substance use) and a bifactor (general factor of non-specific psychopathology, residual factors characterized as internalizing and thought disorder), which both had good fit and full measurement invariance across age, sex, and enrollment date. CONCLUSIONS: Our findings confirm that the DSM-XC may be conceptualized as a multidimensional instrument and provide a scoring solution for researchers who wish to measure distinct constructs. Future research on the psychometric profile of the DSM-XC is needed, focused on the validity of these candidate solutions and their performance across research populations and settings.