Toward Pre-Diagnostic Detection of Dementia in Primary Care.

BACKGROUND: Preventing dementia warrants the pragmatic engagement of primary care. OBJECTIVE: This study predicted conversion to dementia 12 months before diagnosis with indicators that primary care can utilize within the practical constraints of routine practice. METHODS: The study analyzed data from the Alzheimer's Disease Neuroimaging Initiative (Total sample = 645, converting participants = 54). It predicted the conversion from biological (plasma neurofilament light chain), cognitive (Trails Making Test- B), and functional (Functional Activities Questionnaire) measures, in addition to demographic variables (age and education). RESULTS: A Gradient Booster Trees classifier effectively predicted the conversion, based on a Synthetic Minority Oversampling Technique (n = 1,290, F1 Score = 92, AUC = 94, Recall = 87, Precision = 97, Accuracy = 92). Subsequent analysis indicated that the MCI False Positive group (i.e., non-converting participants with cognitive impairment flagged by the model for prospective conversion) scored significantly lower on multiple cognitive tests (Montreal Cognitive Assessment, p < 0.002; ADAS-13, p < 0.0004; Rey Auditory Verbal Learning Test, p < 0.002/0.003) than the MCI True Negative group (i.e., correctly classified non-converting participants with cognitive impairment). These groups also differed in CSF tau levels (p < 0.04), while consistent effect size differences emerged in the all-pairwise comparisons of hippocampal volume and CSF Aß1 - 42. CONCLUSION: The model effectively predicted 12-month conversion to dementia and further identified non-converting participants with MCI, in the False Positive group, at relatively higher neurocognitive risk. Future studies may seek to extend these results to earlier prodromal phases. Detection of dementia before diagnosis may be feasible and practical in primary care settings, pending replication of these findings in diverse clinical samples.

Subjective Versus Objective Assessment of Cognitive Functioning in Primary Care.

PURPOSE: This study examined the clinical utility of highly efficient subjective and objective screens of cognitive impairment. METHOD: Participants (N = 124, age ≥ 65, mean = 73.59, SD = 6.26) completed a 2-item questionnaire of subjective memory functioning, a brief computerized cognitive test, and the Montreal Cognitive Assessment (MoCA). Next, participants were assigned to 1 of 4 conditions, based on their subjective (low/high) and objective (impaired/unimpaired) levels of cognitive functioning. Further analysis divided the sample into age-based groups (ie, age < 75, age ≥ 75). RESULTS: The proportion of participants in the impaired subsample (ie, MoCA < 26), who reported a high level of subjective concern about their memory, was low (ie, 0.15). Among unimpaired participants, analysis detected significant group differences across subjective memory levels (P < .0003) and age (P < .005) categories on one of the three tasks of the computerized test (ie, cognitive control). In contrast, the MoCA offered no differentiation between these groups. CONCLUSION: Screening protocols in which cognitive testing is administered subsequent to patient complaint are prone to underdiagnosis. In addition, common dementia screens are insensitive to subjective deficits and healthy cognitive aging. Therefore, they may lead to dismissing valid concerns that deserve preventive attention. Primary care needs efficient screening tools that are sensitive to prodromal decline.

Machine Learning Enhances the Efficiency of Cognitive Screenings for Primary Care.

BACKGROUND: Incorporation of cognitive screening into the busy primary care will require the development of highly efficient screening tools. We report the convergence validity of a very brief, self-administered, computerized assessment protocol against one of the most extensively used, clinician-administered instruments-the Montreal Cognitive Assessment (MoCA). METHOD: Two hundred six participants (mean age = 67.44, standard deviation [SD] = 11.63) completed the MoCA and the computerized test. Three machine learning algorithms (ie, Support Vector Machine, Random Forest, and Gradient Boosting Trees) were trained to classify participants according to the clinical cutoff score of the MoCA (ie, < 26) from participant performance on 25 features of the computerized test. Analysis employed Synthetic Minority Oversampling TEchnic to correct the sample for class imbalance. RESULTS: Gradient Boosting Trees achieved the highest performance (accuracy = 0.81, specificity = 0.88, sensitivity = 0.74, F1 score = 0.79, and area under the curve = 0.81). A subsequent K-means clustering of the prediction features yielded 3 categories that corresponded to the unimpaired (mean = 26.98, SD = 2.35), mildly impaired (mean = 23.58, SD = 3.19), and moderately impaired (mean = 17.24, SD = 4.23) ranges of MoCA score ( F = 222.36, P < .00). In addition, compared to the MoCA, the computerized test correlated more strongly with age in unimpaired participants (ie, MoCA ≥26, n = 165), suggesting greater sensitivity to age-related changes in cognitive functioning. CONCLUSION: Future studies should examine ways to improve the sensitivity of the computerized test by expanding the cognitive domains it measures without compromising its efficiency.

Developing Cognitive Markers of Alzheimer's Disease for Primary Care: Implications for Behavioral and Global Prevention.

A comprehensive approach to the prevention of Alzheimer's disease (AD) warrants a synergy across multiple domains and procedures. Whereas the study of biological markers has mobilized major activity in the field, the development of cognitive markers is largely ignored, despite the unique advantages they may offer. Cognitive markers essentially assess the core clinical feature that biological markers intend to predict. In this respect, cognitive markers expand the foundation of preclinical diagnostics and disease staging in a manner that integrates both physiological and psychological factors. In addition, the cost-effective implementation of cognitive markers makes them remarkably conducive to community-wide screenings, and thereby a vital component of any global blueprint for prevention. Specifically, in the primary care setting, cognitive markers may provide effective gate keeping for more invasive, labor intensive, and expensive procedures. From this perspective, cognitive markers may provide the first step for identifying preclinical treatment recipients in general public. Moreover, the detection of preclinical decline via cognitive markers can increase awareness of AD risk and the motivation for making protective lifestyle changes. The behavioral approach might be expedient for prevention in light of the compelling evidence of lifestyle amelioration of AD risk. In an integrative view, incorporating cognitive markers to primary care may facilitate a synergetic development in preventive interventions that carries epidemiological significance. This paper addresses the theoretical, methodological, and pragmatic aspects of this prospect.

Stigma, social anxiety, and illness severity in bipolar disorder: Implications for treatment.

BACKGROUND: Studies indicate that comorbid anxiety disorders predict a more severe course of illness in bipolar disorder (BD). The relatively high prevalence of social anxiety in BD points to the potential role that socio-cultural factors, such as stigma, play in exacerbating the progression of this disorder. Stigma creates social anxiety in affected individuals because it essentially forces them into a vulnerable social status that is marked by public disgrace. Although the etiology of debilitating social anxiety in BD may involve multiple factors, stigma deserves particular clinical attention because research in this area indicates that it is common and its internalization is associated with poor outcome. METHODS: We conducted a literature review using search terms related to stigma, social anxiety, bipolar disorder, illness severity, and outcomes. The electronic databases searched included PsychINFO, PubMed, JSTOR, and EBSCOhost Academic Search Complete with limits set to include articles published in English. RESULTS: The literature indicates that internalized stigma often triggers the core psychological experiences of social anxiety and is highly correlated with clinical and functional outcome in BD. On a psychological level, internalized stigma and social anxiety can create distress that triggers symptoms of BD. From a biological perspective, stigma constitutes a chronic psychosocial stressor that may interact with the pathophysiology of BD in inflammatory ways. CONCLUSIONS: The connection between stigma and social anxiety, and their combined effects on people with BD, carries important implications for psychiatric care. To obtain an accurate clinical formulation, initial evaluations may seek to examine stigma-related experiences and determine their relationship to anxiety symptoms and psychosocial functioning. In addition, direct interventions for reducing the ill effects of stigma in BD deserve clinical attention, because they may carry the potential to enhance outcomes.

Illness severity, trait anxiety, cognitive impairment and heart rate variability in bipolar disorder.

Numerous studies have documented a significant association between symptom severity and cognitive functioning in bipolar disorder (BD). These findings advanced speculations about a potential link between the physiological stress associated with illness severity and cognitive dysfunction. To explore this hypothesis, the current study employed heart rate variability (HRV) as a physiological measure that is sensitive to the effects of chronic stress, and a scale of trait anxiety for assessing a psychological condition that is correlated with hyper sympathetic arousal. Analyses indicated that BD patients with High Illness Severity reported more symptoms of trait-anxiety (i.e., State Trait Anxiety Inventory), performed more poorly on a computerized neuropsychological battery (i.e., CNS Vital Signs), and exhibited a more constricted HRV profile (i.e., lower SDNN with elevated LF/HF ratio) than patients with Low Illness Severity. Illness severity was determined by a history of psychosis, illness duration, and number of mood episodes. A third group of healthy controls (n=22) performed better on the neuropsychological battery and exhibited a healthier HRV profile than the BD groups. This study provides preliminary evidence that illness severity and cognitive impairment in BD may be associated with state anxiety and neuro-cardiac alterations that are sensitive to physiological stress.

Neuropsychological screening as a standard of care during discharge from psychiatric hospitalization: the preliminary psychometrics of the CNS Screen.

Cost-prohibitive factors currently prevent a warranted integration of neuropsychological screenings into routine psychiatric evaluations, as a standard of care. To overcome this challenge, the current study examined the psychometric properties of a new computerized measure-the CNS Screen. One hundred and twenty six psychiatric inpatients completed the CNS Screen, the Montreal Cognitive Assessment (MoCA), and the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR16) on the day of hospital discharge. Statistical analysis established convergent validity with a moderate correlation between the self-administered CNS Screen and the clinician-administered MoCA (r=0.64). Discriminant validity was implicated by a non-significant correlation with the QIDS-SR16. Concurrent validity was supported by a moderate, negative correlation with patients' age (r=-0.62). In addition, consistent with previous findings, patients with psychotic disorders exhibited significantly poorer performance on the CNS Screen than patients with a mood disorder. Similarly, patients with a formal disability status scored significantly lower than other patients. The CNS Screen was well tolerated by all patients. With further development, this type of measure may provide a cost-effective approach to expanding neuropsychological screenings on inpatient psychiatric units.

Cognitive and psychosocial functioning in bipolar disorder with and without psychosis during early remission from an acute mood episode: a comparative longitudinal study.

BACKGROUND: The current investigation aimed to extend previous findings, which linked psychosis in bipolar disorder (BD) to cognitive impairment during hospital discharge and readmission, by examining the recovery of patients with psychosis who were not re-hospitalized. The study compared mood, cognitive and functional outcomes in patients who had, versus had not, experienced psychosis during a recent psychiatric hospitalization. The hypothesis was that patients admitted to the hospital with psychosis would exhibit more residual symptoms, greater cognitive deficits, and lower psychosocial functioning than patients who presented to care without psychosis. Group differences were expected to emerge both at the time of hospital discharge and at a 3-month follow up. METHOD: Fifty-five participants (ages 18-59, 25 women, 20 with psychosis) with BD I disorder completed both assessments, which included a clinical and diagnostic interview, functional evaluation, and the administration of mood measures and a neuropsychological battery. RESULTS: The groups were comparable with respect to illness history (e.g., number of previous hospitalizations, age of onset, employment). At discharge and follow-up, the group with psychosis exhibited more mood symptoms, obtained lower GAF scores, and performed more poorly on measures of memory and executive functioning. At follow-up, participants with psychosis exhibited poorer psychosocial adaptation. LIMITATIONS: It is possible that some of the observed group differences in cognitive functioning emerged due to differences in medication efficacy or side effects. CONCLUSION: The results of this study support the hypothesis that psychosis in BD predicts limited recovery during early remission from mood disturbance, regardless of illness history.

Autonomic nervous system arousal and cognitive functioning in bipolar disorder.

OBJECTIVE: Previous theories about the etiology of cognitive dysfunction in bipolar disorder (BD) emphasized trait factors such as neurological impairment. State factors, other than mood symptoms, that may exacerbate functional deficits have not yet been considered. The purpose of this study was to examine autonomic nervous system (ANS) arousal following cognitive challenge. The study compared patients with BD and healthy controls (HC) in physiological measures and neuropsychological test scores. METHODS: Thirty euthymic patients with BD and 22 HC completed the study. Participants completed mood [Beck Depression Inventory-II (BDI-II) and Young Mania Rating Scale (YMRS)], anxiety (State-Trait Anxiety Inventory), and substance abuse (Drug Abuse Screening Test-20 item and Alcohol Use Disorders Identification Test) measures. They were connected to an electrogram, a sensitive thermometer for measuring finger temperature, and electrodes that measure galvanic skin response. After a five-min baseline measurement in a restful state, participants completed a computerized neuropsychological battery (CNS Vital Signs). RESULTS: The group with BD reported significantly more mood symptoms (BDI-II, t = 3.71, p < 0.001; YMRS, t = 6.73, p < 0.001) and scored higher on a measure of trait-anxiety (State-Trait Anxiety Inventory, t = 2.91, p < 0.001) than HC. A multivariate analysis of variance revealed higher arousal on all physiological measures in the BD group relative to HC at baseline [F(3,48) = 13.1, p < 0.001] and during cognitive testing [F(3,48) = 11.3, p < 0.001]. The increase in physiological arousal from a restful state to the time of testing was higher for the BD group [F(3,37) = 8.06, p < 0.001]. With respect to cognitive data, HC scored higher than patients with BD across the measures of memory (F = 8.5, p < 0.001), sustained (F = 9.5, p < 0.001) and complex (F = 2.7, p < 0.04) attention, processing speed (F = 10.0, p < 0.001), reaction time (F = 7.8, p < 0.001), cognitive flexibility (F = 19.7, p < 0.001), working memory (F = 10.8, p < 0.001), and social acuity (F = 5.7, p < 0.01), with partial eta-squared from 0.18 to 0.62. Correlational analysis revealed significant associations between various cognitive test scores and changes in physiological arousal from baseline to testing (-0.59 ≤ r ≤ 0.22). CONCLUSIONS: Relative to HC, patients with BD experience larger changes in ANS arousal between a restful baseline and cognitive testing, and achieve lower cognitive test scores. Further research is needed to determine whether acute physiological symptoms of anxiety directly compromise cognitive functioning in BD.

Recovery of cognitive functioning in patients with co-occurring bipolar disorder and alcohol dependence during early remission from an acute mood episode.

OBJECTIVE: This study aimed to examine cognitive recovery in patients with co-occurring bipolar disorder (BD) and alcohol dependence (AD) during remission from an acute mood disturbance. METHOD: Fifty-five adult inpatients with bipolar I disorder (BD I) completed a neuropsychological battery, mood measures, and substance abuse measures upon discharge from the hospital and at a 3-month follow-up. Analyses provided group comparisons on these measures between patients who presented with co-occurring AD (n = 21) in the year prior to hospital admission and patients without a substance use disorder (SUD; n = 34). RESULTS: Multivariate analyses of variance detected group differences on measures of visual memory, verbal memory, and executive functioning, using previous number of psychiatric admissions and age of onset of BD as covariates. These differences occurred both at discharge and follow-up. Between discharge and follow-up, the group without SUD exhibited more substantial gains than the group of dually diagnosed patients on free recall of verbal and visual materials and on a measure of cognitive flexibility. CONCLUSIONS: Patients with co-occurring BD and AD may suffer from more severe cognitive dysfunction and less favorable recovery of cognitive deficits than patients without SUD over the course of remission from a mood episode.

Functional outcome in bipolar disorder: the big picture.

Previous research on functional outcome in bipolar disorder (BD) has uncovered various factors that exacerbate psychosocial disability over the course of illness, including genetics, illness severity, stress, anxiety, and cognitive impairment. This paper presents an integrated view of these findings that accounts for the precipitous decline in psychosocial functioning after illness onset. The proposed model highlights a number of reciprocal pathways among previously studied factors that trap people in a powerful cycle of ailing forces. The paper discusses implications to patient care as well as the larger social changes required for shifting the functional trajectory of people with BD from psychosocial decline to growth.

The characteristics of a discrete mood episode, neuro-cognitive impairment and re-hospitalization in bipolar disorder.

This longitudinal study examined characteristics of a discrete mood episode that predict re-hospitalization for bipolar disorder, highlighting associated cognitive dysfunction as a potential mechanism linking episode severity and relapse. Eighty-two inpatients meeting DSM-IV-TR diagnostic criteria for bipolar I disorder completed the study. Twenty-two of the patients were readmitted to the hospital within 3 months of discharge. The study compared these patients to the remaining 60 patients who were not readmitted to the hospital during this period. Patients were compared on several factors related to the severity of the mood episode and the course of illness more generally. Analysis also compared the groups on measures of mood and neuro-cognitive functioning, assessed 24-48 h before initial hospitalization discharge. Re-hospitalized patients had longer initial hospital stays (t = -3.10, p < 0.01), higher rates of psychosis while in the hospital (Chi square = 5.1, p < 0.02), and lower GAF scores on discharge (t = 2.37, p < 0.05). The groups did not differ in age of illness onset or number of previous psychiatric hospitalizations. With respect to neuro-cognitive functioning, analysis indicated poorer performance for re-hospitalized patients on measures of executive functioning (Wilks' Lambda, F (7, 71) = 9.0, p < 0.001), IQ (Wilks' Lambda, F (2, 76) = 5.06, p < 0.01), and memory (Wilks' Lambda, F (6,72) = 4.19, p < 0.001). Trends in the expected direction emerged for attention/working memory tests (Wilks' Lambda, F (7, 71) = 1.79, p < 0.10). Results highlight features of a discrete mood episode associated with increased rates of re-hospitalization. This study observed connections among episode severity, cognitive dysfunction at hospital discharge and re-hospitalization.

Ecologically valid support for the link between cognitive and psychosocial functioning in bipolar disorder.

Prior research into the link between cognitive and psychosocial functioning in bipolar disorder has examined primarily asymptomatic patients, has measured these domains concurrently, and has failed to establish convergent validity in the assessment of psychosocial dysfunction. The present study examines the relation between cognitive and psychosocial functioning at the time of discharge from hospitalization for acute mood disturbance. We obtained measures of psychosocial functioning that were both close and distant to the time of neuropsychological testing; the former from the discharging psychiatrists, and the latter from reports of formally recognized disability status, determined by persons wholly unrelated to the present research. Sixty-three patients with bipolar I disorder, hospitalized for acute mood disturbance, completed a neuropsychological test battery 24 to 48 h prior to discharge. We compared patients with versus without formal disability status on the Global Assessment of Functioning (GAF) scale and on scores of neuropsychological tests. We also tested associations between GAF scores and cognitive test scores. Results supported the convergent validity in the measurement of psychosocial disability, underscored the robust connection between cognitive and psychosocial impairment, and highlighted the presence of this connection during an important clinical state - time of discharge from psychiatric hospitalization.

Cognitive impairment in bipolar disorder: an overview.

Research on cognitive impairment in bipolar disorder (BD) has prompted significant insights about the illness. New studies challenge previous notions about the episodic nature of BD, and account for psychosocial disability unrelated to mood disturbance. This article provides a conceptual overview of the growing body of research on cognitive dysfunction in BD. We discuss the evidence in light of the complexity inherent in the connection between cognitive deficits and neurological abnormalities in BD. This article also addresses issues related to etiology, advancing an integration of neurological, clinical, cognitive, and psychosocial factors into a model that elucidates how these factors interact to negatively impact persons with BD with a more severe course of illness. Lastly, this article discusses implications for patient care and future considerations.

Neurocognitive impairment and psychosis in bipolar I disorder during early remission from an acute episode of mood disturbance.

OBJECTIVE: Recent studies have reported greater neurocognitive impairment in euthymic bipolar disorder patients with a history of psychosis relative to patients without such a history. To further explore the relation between psychosis and cognitive dysfunction in bipolar disorder, the current study examined the cognitive functioning of patients during early remission from a discrete episode of mood disturbance. The study aimed to determine whether the presence of psychosis during inpatient hospitalization was associated with greater cognitive impairment at the time of hospital discharge. METHOD: Fifty-nine inpatients who met DSM-IV criteria for bipolar disorder (24 admitted with psychosis, 35 admitted without psychosis), ages 18-59 years, completed a neuropsychological battery and mood measures 24-48 hours before discharge. The cognitive battery included standardized tests of IQ, attention and working memory, visual memory, verbal memory, and executive functioning. RESULTS: A multivariate analysis of variance detected group differences on measures of verbal memory (P < .001) and executive functioning (P < .003), using mood measures and previous number of psychiatric admissions as covariates. Post hoc analysis of between-subjects effects revealed significantly poorer performance on the California Verbal Learning Test-Second Edition, logical memory subtest from Wechsler Memory Scale-Revised, Stroop Word/Color Interference test, and the Wisconsin Card Sorting Test for patients who were admitted to the hospital with psychosis. These results remained significant after matching the groups for past psychosis, with the exception of the logical memory subtest. CONCLUSIONS: The results of this study indicate that patients with bipolar disorder who were admitted to the hospital due to psychosis exhibited significantly more severe cognitive impairment at the time of discharge than patients admitted for an acute mood disturbance without psychosis. These findings may be important for improving discharge planning and the development of more effective outpatient services.

The duration of inpatient admission predicts cognitive functioning at discharge in patients with bipolar disorder.

Previous studies of cognitive functioning in bipolar disorder generally indicate that a more severe course of illness is associated with greater cognitive impairment. In particular, a history of greater number and longer duration of mood episodes predicts enduring cognitive deficits in euthymic patients. Shifting the focus of this investigation to the cognitive effects of a discrete mood episode, the current study aimed to explore whether patients who require a longer hospitalization to stabilize from an acute episode of mood disturbance present with more compromised cognitive functioning during the phase of early recovery. For this purpose, the study examined the link between the duration of inpatient admission and neuropsychological test scores at the time of discharge in 41 patients with bipolar disorder. Participants were assigned to long (n = 20) and short (n = 21) stay groups using a median split (M = 12). Results indicated that longer admissions were associated with more severe deficits in executive functioning at discharge after controlling for residual mood symptoms and previous number of psychiatric admissions. Findings from the current study may inform discharge planning for patients with bipolar disorder after an extended hospital stay.

Neurocognitive impairment in patients with co-occurring bipolar disorder and alcohol dependence upon discharge from inpatient care.

The current study explored the neurocognitive functioning of patients with co-occurring bipolar disorder and alcohol dependence upon discharge from inpatient care. The study compared scores of neuropsychological tests among three groups of bipolar I inpatients without a history of neurological injury or illness: 1) patients meeting DSM-IV diagnostic criteria for alcohol dependence in the past 6 months (n=13), 2) patients diagnosed with alcohol dependence in full remission (n=9), and 3) patients without a history of a substance use disorder (SUD; n=41). Analyses indicated that patients with co-occurring alcohol dependence exhibited more severe impairment on tests of executive functioning (i.e. Stroop Color-Word Interference Test, Wisconsin Card Sorting Test) than patients without SUD. In addition, the group meeting diagnostic criteria for alcohol dependence in the past 6 months exhibited greater decrements in verbal (California Verbal Learning Test--II) and visual (Rey Complex Figure Test) memory. Analysis further indicated that patients in full SUD remission scored lower on measures of fluid intelligence (Wechsler Abbreviated Scale of Intelligence--Performance IQ). Consistent with previous reports, in the current sample, co-occurring alcohol dependence predicted higher rates of disability status. It is possible that cognitive deficits of greater severity in dually diagnosed patients contribute to this unfavorable outcome. Recognizing the extent of cognitive impairment in dually diagnosed patients may facilitate the effort to ameliorate their condition.

Gender differences in the motivational processing of facial beauty.

Gender may be involved in the motivational processing of facial beauty. This study applied a behavioral probe, known to activate brain motivational regions, to healthy heterosexual subjects. Matched samples of men and women were administered two tasks: (a) key pressing to change the viewing time of average or beautiful female or male facial images, and (b) rating the attractiveness of these images. Men expended more effort (via the key-press task) to extend the viewing time of the beautiful female faces. Women displayed similarly increased effort for beautiful male and female images, but the magnitude of this effort was substantially lower than that of men for beautiful females. Heterosexual facial attractiveness ratings were comparable in both groups. These findings demonstrate heterosexual specificity of facial motivational targets for men, but not for women. Moreover, heightened drive for the pursuit of heterosexual beauty in the face of regular valuational assessments, displayed by men, suggests a gender-specific incentive sensitization phenomenon.