A Rapid, Mobile Neurocognitive Screening Test to Aid in Identifying Cognitive Impairment and Dementia (BrainCheck): Cohort Study.

BACKGROUND: The US population over the age of 65 is expected to double by the year 2050. Concordantly, the incidence of dementia is projected to increase. The subclinical stage of dementia begins years before signs and symptoms appear. Early detection of cognitive impairment and/or cognitive decline may allow for interventions to slow its progression. Furthermore, early detection may allow for implementation of care plans that may affect the quality of life of those affected and their caregivers. OBJECTIVE: We sought to determine the accuracy and validity of BrainCheck Memory as a diagnostic aid for age-related cognitive impairment, as compared against physician diagnosis and other commonly used neurocognitive screening tests, including the Saint Louis University Mental Status (SLUMS) exam, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). METHODS: We tested 583 volunteers over the age of 49 from various community centers and living facilities in Houston, Texas. The volunteers were divided into five cohorts: a normative population and four comparison groups for the SLUMS exam, the MMSE, the MoCA, and physician diagnosis. Each comparison group completed their respective assessment and BrainCheck Memory. RESULTS: A total of 398 subjects were included in the normative population. A total of 84 participants were in the SLUMS exam cohort, 51 in the MMSE cohort, 35 in the MoCA cohort, and 18 in the physician cohort. BrainCheck Memory assessments were significantly correlated to the SLUMS exam, with coefficients ranging from .5 to .7. Correlation coefficients for the MMSE and BrainCheck and the MoCA and BrainCheck were also significant. Of the 18 subjects evaluated by a physician, 9 (50%) were healthy, 6 (33%) were moderately impaired, and 3 (17%) were severely impaired. A significant difference was found between the severely and moderately impaired subjects and the healthy subjects (P=.02). We derived a BrainCheck Memory composite score that showed stronger correlations with the standard assessments as compared to the individual BrainCheck assessments. Receiver operating characteristic (ROC) curve analysis of this composite score found a sensitivity of 81% and a specificity of 94%. CONCLUSIONS: BrainCheck Memory provides a sensitive and specific metric for age-related cognitive impairment in older adults, with the advantages of a mobile, digital, and easy-to-use test. TRIAL REGISTRATION: ClinicalTrials.gov NCT03608722; https://clinicaltrials.gov/ct2/show/NCT03608722 (Archived by WebCite at http://www.webcitation.org/76JLoYUGf).

Diagnostic accuracy of tablet-based software for the detection of concussion.

Despite the high prevalence of traumatic brain injuries (TBI), there are few rapid and straightforward tests to improve its assessment. To this end, we developed a tablet-based software battery ("BrainCheck") for concussion detection that is well suited to sports, emergency department, and clinical settings. This article is a study of the diagnostic accuracy of BrainCheck. We administered BrainCheck to 30 TBI patients and 30 pain-matched controls at a hospital Emergency Department (ED), and 538 healthy individuals at 10 control test sites. We compared the results of the tablet-based assessment against physician diagnoses derived from brain scans, clinical examination, and the SCAT3 test, a traditional measure of TBI. We found consistent distributions of normative data and high test-retest reliability. Based on these assessments, we defined a composite score that distinguishes TBI from non-TBI individuals with high sensitivity (83%) and specificity (87%). We conclude that our testing application provides a rapid, portable testing method for TBI.

Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus.

BACKGROUND: Positron emission tomography (PET) studies of major depression have revealed resting-state abnormalities in the prefrontal and cingulate cortices. Recently, fMRI has been adapted to examine connectivity within a specific resting-state neural network--the default-mode network--that includes medial prefrontal and anterior cingulate cortices. The goal of this study was to examine resting-state, default-mode network functional connectivity in subjects with major depression and in healthy controls. METHODS: Twenty-eight subjects with major depression and 20 healthy controls underwent 5-min fMRI scans while resting quietly. Independent component analysis was used to isolate the default-mode network in each subject. Group maps of the default-mode network were compared. A within-group analysis was performed in the depressed group to explore effects of depression refractoriness on functional connectivity. RESULTS: Resting-state subgenual cingulate and thalamic functional connectivity with the default-mode network were significantly greater in the depressed subjects. Within the depressed group, the length of the current depressive episode correlated positively with functional connectivity in the subgenual cingulate. CONCLUSIONS: This is the first study to explore default-mode functional connectivity in major depression. The findings provide cross-modality confirmation of PET studies demonstrating increased thalamic and subgenual cingulate activity in major depression. Further, the within-subject connectivity analysis employed here brings these previously isolated regions of hypermetabolism into the context of a disordered neural network. The correlation between refractoriness and subgenual cingulate functional connectivity within the network suggests that a quantitative, resting-state fMRI measure could be used to guide therapy in individual subjects.

Cortisol circadian rhythm alterations in psychotic major depression.

BACKGROUND: Increased hypothalamic-pituitary-adrenal axis activity is well described in psychotic depression with an emphasis on 24-hour, urinary free cortisol levels or dexamethasone suppression tests. There are limited data on cortisol levels during specific times of the day. METHODS: Patients with depression with (PMD) and without (NPMD) psychosis and healthy control subjects were studied using rating scales of depression and psychosis and measures of HPA activity, including overnight cortisol and adrenocorticotropin levels. We used analysis of variance to determine group differences and regression analyses to assess contributions of specific measures to cortisol levels. RESULTS: PMDs had higher cortisol during the evening hours than did NPMDs or control subjects, who did not differ from one another. Regression analyses suggest that depression and the combination of depressive and psychotic symptoms were important contributors to variance in evening cortisol. CONCLUSIONS: PMD is associated with increased cortisol levels during the quiescent hours. Enhanced cortisol activity, particularly a higher nadir, was related to depression severity and the interaction of depressive and psychotic symptoms. This increase suggests a defect in the action of the circadian timing system and HPA axis, creating a hormonal milieu similarly seen in early Cushing's syndrome and potentially an (im)balance of mineralocorticoid and glucocorticoid receptor activity.

The neuropsychological profile of psychotic major depression and its relation to cortisol.

BACKGROUND: Our study described the neuropsychological profile of psychotic major depression (PMD) compared to nonpsychotic major depression (NPMD) patients and psychiatrically healthy controls (HC). We predicted that higher cortisol levels would be associated with greater cognitive deficits. METHODS: Twenty-nine PMDs, 24 NPMDs, and 26 HCs were recruited at Stanford University Medical Center. Psychiatric ratings, cortisol levels from 1800-0900 hours, and neuropsychological test data were obtained. RESULTS: PMDs had more severe cognitive impairments compared with NPMDs and HCs with the exception of simple verbal attention. PMDs had elevated mean cortisol levels from 1800 to 0100 hours which were significantly correlated with poorer verbal memory and psychomotor speed performance. Cortisol slopes from 1800 to 0100 hours were also significantly correlated with verbal memory and working memory. CONCLUSIONS: While PMDs' ability to attend passively to information appears intact, they have more difficulty processing, manipulating, and encoding new information. Elevated cortisol levels, as seen in PMD patients, are associated with poorer cognitive performance especially related to verbal memory for lists of words and working memory.

Clinical and biological effects of mifepristone treatment for psychotic depression.

Psychotic major depression (PMD) is found to be a relatively common psychiatric condition that affects up to nearly 20% of patients with major depression. Previous studies by our group have shown rapid reversal of psychotic symptoms in some PMD patients treated with mifepristone, in addition to restoring a more normal afternoon cortisol release. The rationale for treating patients with PMD with a glucocorticosteroid receptor antagonist is further discussed. In total, 30 patients with PMD were treated with either 600 mg/day mifepristone or placebo for 8 days in a randomized double-blind manner. The Hamilton Depression Rating Scale (HDRS) and the Brief Psychiatric Rating Scale (BPRS) were administered at baseline and again after 8 days of treatment. Cortisol and ACTH were measured hourly from 1800 to 0900 at baseline and after 8 days of treatment. Significantly, more patients in the mifepristone group (seven of 15) showed a 50% or greater decline on the BPRS positive symptom subscale, an index of psychotic symptoms, as compared to the placebo group (two of 15). Patients who received mifepristone had lower HDRS and BPRS scores at study completion compared to those who received placebo, but these differences were not statistically significant. In addition, mifepristone significantly elevated cortisol and ACTH levels and steepened ascending slopes from 1800 to 0100 and from 0100 to 0900 as compared to placebo. Clinical and biological effects of mifepristone were comparable among males and females. Age was found to significantly and positively correlate with changes in cortisol and ACTH. These results suggest that short-term use of mifepristone may be effective in the treatment of PMD and may re-regulate the HPA axis. Additional blinded studies are warranted.

Detecting psychotic major depression using psychiatric rating scales.

OBJECTIVE: The aim of this study was to assess whether individual or clusters of psychiatric symptoms can differentiate patients with psychotic major depression (PMD) from those with nonpsychotic depression (NPMD). METHOD: Data were pooled from two studies investigating patients with moderate depression. A total of 129 subjects were studied. Patients in Sample 1 were unmedicated, while the majority of the patients in Sample 2 were taking psychotropic medications. Baseline rating scales were obtained for all subjects, including the Hamilton depression rating scale and the brief psychiatric rating scale (BPRS). We used discriminant function analyses, logistic regression, and ROC analyses to determine the patterns in symptoms that differentiated the groups. RESULTS: Psychotic patients were adequately differentiated by the unusual thought content (UTC) item of the BPRS. Even mild UTC endorsement was an indicator of PMD. Furthermore, results suggest that the positive symptom subscale of the BPRS was even better at differentiating PMD from NMPD patients. Sensitivity and specificity for this scale were 84% and 99%, respectively. CONCLUSION: Psychotic major depression is often undiagnosed and poorly treated. One reason for this trend is the failure of physicians to inquire in a more detailed manner about positive symptoms in patients with primary mood symptoms. Although physicians are not likely to have the time to conduct an entire BPRS during an evaluation, our results suggest that a few key symptoms, if assessed directly, may aid the psychiatrist to more effectively diagnose and subsequently treat their depressed patients.