Kevin J. Manning

Diagnosis and treatment of depression and cognitive impairment in late life

Cognitive impairment in late‐life depression is prevalent, disabling, and heterogeneous. Although mild cognitive impairment in depression does not usually progress to dementia, accurate assessment of cognition is vital to prognosis and treatment planning. For example, executive dysfunction often accompanies late‐life depression, influences performance across cognitive domains, and is associated with poor antidepressant treatment outcomes. Here, we review how assessment can capture dysfunction across cognitive domains and discuss cognitive trajectories frequently observed in late‐life depression in the context of the neurobiology of this disorder. We also review the efficacy of a sample of interventions tailored to specific cognitive profiles.

Effect of Cognitive Status on Self-Regulatory Driving Behavior in Older Adults: An Assessment of Naturalistic Driving Using In-Car Video Recordings

Previous findings that older drivers engage in strategic self-regulatory behaviors to minimize perceived safety risks are primarily based on survey reports rather than actual behavior. This study analyzed in-car video recording of naturalistic driving of 18 patients with Alzheimer disease (AD) and 20 age-matched controls in order to (1) characterize self-regulatory behaviors engaged by older drivers and (2) assess how behaviors change with cognitive impairment. Only participants who were rated “safe” on a prior standardized road test were selected for this study. Both groups drove primarily in environments that minimized the demands on driving skill and that incurred the least risk for involvement in major crashes. Patients with AD displayed further restrictions of driving behavior beyond those of healthy elderly individuals, suggesting additional regulation on the basis of cognitive status. These data provide critical empirical support for findings from previous survey studies indicating an overall reduction in driving mobility among older drivers with cognitive impairment.

Patterns of Word-List Generation in Mild Cognitive Impairment and Alzheimer's Disease

Patients with amnestic mild cognitive impairment (aMCI) have been described as exhibiting greater impairment on tests of category fluency than letter fluency. This has been offered as evidence that this condition represents pre-clinical Alzheimers disease (AD). We hypothesized that this pattern of differential impairment is dependent on the specific semantic categories and initial letters selected, and is not specific to AD and aMCI. A total of 40 cognitively normal older adults, 74 MCI patients—25 “amnestic single domain” (aMCI), 27 “amnestic multiple domain”, and 22 non-amnestic—and 29 AD patients were tested with multiple forms of semantic-category and initial-letter fluency tasks. The pattern of deficits within and across groups was highly dependent on the specific categories and letters chosen. Overall, aMCI patients did not demonstrate greater impairment in category than letter fluency. In fact, the level and pattern of their performance resembled that of cognitively normal older adults much more than AD patients. MCI patients with deficits in multiple cognitive domains performed most like AD patients. These findings indicate that verbal fluency performance is highly influenced by the specific tasks used, and impairment on semantic fluency is not characteristic of pure amnestic MCI.

Medication Management and Neuropsychological Performance in Parkinson's Disease

Medication non-adherence is associated with chronic disease and complex medication schedules, and Parkinsons disease (PD) patients also frequently have cognitive impairments that may interfere with effective medication management. The current study quantitatively assessed the medication management skills of PD patients and probed the neurocognitive underpinnings and clinical correlates of this skill. A total of 26 men with PD completed a neuropsychological battery and a modified version of the Hopkins Medication Schedule (HMS), a standard test of a persons ability to understand and implement a routine prescription medication. Estimated adherence rates from performance on the HMS were low. Memory, executive functioning, and processing speed were strongly related to different components of the HMS. A range of neuropsychological abilities is associated with the ability to understand and implement a medication schedule and pillbox in individuals with PD.

Vision and Driving in Multiple Sclerosis

OBJECTIVE To examine the relationship between measures of visual dysfunction and driving performance in persons with multiple sclerosis (MS). DESIGN Between-group comparison. SETTING All data were collected in an outpatient research setting. PARTICIPANTS Persons (N=66) with MS of the relapsing remitting type (26 self-reporting visual difficulties; 40 self-reporting no visual difficulties) and 26 age- and sex-matched healthy controls. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Measures of vision included visual acuity, depth perception, and color perception. Driving was measured using documented accident/violation rate and self-reported driving behaviors. RESULTS Quantitative analysis only revealed that MS persons with self-reported visual difficulties performed significantly worse than healthy controls on color perception (Kruskal-Wallis; chi(2)(2)=8.89, P=.01). There were no group differences on driving behaviors, and correlational analysis revealed a lack of relationship between the selected visual (visual acuity, depth perception, color perception) and driving performance measures (documented accident/violation rate and self-limiting driving behaviors). CONCLUSIONS Persons with MS who self-reported difficulties with vision had acceptable visual acuity, despite demonstrating impairment in color perception. The fact that visual acuity remains the most common measure for visual fitness to drive remains problematic. There is a need to further define measures of visual dysfunction relevant to driving among this clinical population.

Clock drawing as a screen for impaired driving in aging and dementia: is it worth the time?

Clock drawing is recommended by medical and transportation authorities as a screening test for unsafe drivers. The objective of the present study was to assess the usefulness of different clock drawing systems as screening measures of driving performance in 122 healthy and cognitively impaired older drivers. Clock drawing was measured using four different scoring systems. Driving outcomes included global ratings of safety and the error rate on a standardized on-road test. Findings revealed that clock drawing was significantly correlated with the driving score on the road test for each of the scoring systems. However, receiver operator curve analyses showed limited clinical utility for clock drawing as a screening instrument for impaired on-road driving performance with the area under the curve ranging from 0.53 to 0.61. Results from this study indicate that clock drawing has limited utility as a solitary screening measure of on-road driving, even when considering a variety of scoring approaches.

Cognitive control, reward-related decision making and outcomes of late-life depression treated with an antidepressant

BACKGROUND Executive processes consist of at least two sets of functions: one concerned with cognitive control and the other with reward-related decision making. Abnormal performance in both sets occurs in late-life depression. This study tested the hypothesis that only abnormal performance in cognitive control tasks predicts poor outcomes of late-life depression treated with escitalopram. METHOD We studied older subjects with major depression (N = 53) and non-depressed subjects (N = 30). Executive functions were tested with the Iowa Gambling Test (IGT), Stroop Color-Word Test, Tower of London (ToL), and Dementia Rating Scale - Initiation/Perseveration domain (DRS-IP). After a 2-week placebo washout, depressed subjects received escitalopram (target daily dose: 20 mg) for 12 weeks. RESULTS There were no significant differences between depressed and non-depressed subjects on executive function tests. Hierarchical cluster analysis of depressed subjects identified a Cognitive Control cluster (abnormal Stroop, ToL, DRS-IP), a Reward-Related cluster (IGT), and an Executively Unimpaired cluster. Decline in depression was greater in the Executively Unimpaired (t = -2.09, df = 331, p = 0.0375) and the Reward-Related (t = -2.33, df = 331, p = 0.0202) clusters than the Cognitive Control cluster. The Executively Unimpaired cluster (t = 2.17, df = 331, p = 0.03) and the Reward-Related cluster (t = 2.03, df = 331, p = 0.0433) had a higher probability of remission than the Cognitive Control cluster. CONCLUSIONS Dysfunction of cognitive control functions, but not reward-related decision making, may influence the decline of symptoms and the probability of remission of late-life depression treated with escitalopram. If replicated, simple to administer cognitive control tests may be used to select depressed older patients at risk for poor outcomes to selective serotonin reuptake inhibitors who may require structured psychotherapy.

Challenges in the Detection of Working Memory and Attention Decrements among Overweight Adolescent Girls

Background: The present study is unique in employing unusually difficult attention and working memory tasks to reveal subtle cognitive decrements among overweight/obese adolescents. It evaluated novel measures of background electroencephalographic (EEG) activity during one of the tasks and tested correlations of these and other measures with psychological and psychiatric predictors of obesity maintenance or progression. Methods: Working memory and sustained attention tasks were presented to 158 female adolescents who were rated on dichotomous (body mass index percentile <85 vs. ≥85) and continuous (triceps skinfold thickness) measures of adiposity. Results: The results revealed a significant association between excess adiposity and performance errors during the working memory task. During the sustained attention task, overweight/obese adolescents exhibited more EEG frontal beta power as well as greater intraindividual variability in reaction time and beta power across task periods than their normal-weight peers. Secondary analyses showed that frontal beta power during the sustained attention task was positively correlated with anxiety, panic, borderline personality features, drug abuse, and loss of control over food intake. Conclusions: The findings suggest that working memory and sustained attention decrements do exist among overweight/obese adolescent girls. The reliable detection of the decrements may depend on the difficulty of the tasks as well as the manner in which performance and brain activity are measured. Future studies should examine the relevance of these decrements to dietary education efforts and treatment response.

Neuroticism Traits Selectively Impact Long Term Illness Course and Cognitive Decline in Late-Life Depression

OBJECTIVES Neuroticism is a broad construct that conveys a predisposition to experience psychological distress and negative mood states. Vulnerability to stress (VS) is one neuroticism trait that has been linked to worse mood and cognitive outcomes in older adults. We hypothesized that elevated VS would be associated with worse illness course and cognitive decline in older adults with late-life major depression (LLD). DESIGN Participants were enrolled in the Neurocognitive Outcomes of Depression in the Elderly (NCODE), a longitudinal investigation of the predictors of poor illness course and cognitive decline in LLD. Participants were followed upwards of 10 years. SETTING NCODE operates in a naturalistic treatment milieu. PARTICIPANTS 112 participants aged 60 and older with a current diagnosis of major depressive disorder. MEASUREMENTS Treatment response was assessed at least every 3 months and more often if clinically needed. Participants also completed the NEO Personality Inventory-Revised (NEO PI-R) and an annual cognitive examination. Neuroticism traits from the NEO PI-R included anxiety, depression, anger-hostility, self-consciousness, impulsivity, and VS. RESULTS Higher neuroticism traits of VS, impulsivity, anger-hostility, and anxiety were associated with worse treatment response over time. High VS was the only neuroticism trait significantly associated with cognitive functioning. High VS negatively influenced the rate of global cognitive decline over time. CONCLUSIONS Individual personality traits within the neuroticism dimension are associated with treatment resistance and cognitive impairment in LLD. It remains to be seen whether these individual traits are associated with different neurobiological substrates and clinical characteristics of LLD.

Negative Affectivity, Aging, and Depression: Results From the Neurobiology of Late-Life Depression (NBOLD) Study

OBJECTIVE Neuroticism is a common yet understudied condition in older adults. We hypothesized that presence of high negativity affectivity (NA), a key feature of neuroticism, would be associated with different prefrontal cortex (PFC) activity and connectivity patterns in depressed and never-depressed older adults. METHODS This is a baseline cross-sectional analysis of a cohort study of 52 depressed and 36 never-depressed older adults. Assessments included NA scores from the Type D Scale-14 and Montgomery-Åsberg Depression Rating Scale scores. All subjects had a 3T brain functional magnetic resonance imaging resting scan, neuronal activity determined by amplitude of low-frequency fluctuations (ALFFs) were obtained, and resting state functional connectivity (FC) analyses were performed. Analyses of covariance were conducted on ALFFs and FC to examine significant differences between groups. RESULTS In the ALFF analyses there were clearly different patterns between depressed and comparison groups in the correlation of ALFFs and NA. The correlation differences between the two groups were significant in the dorsomedial PFC, insula, amygdala, and posterior cingulate cortex (PCC). FC analyses revealed different between-group connectivity patterns. Significantly higher ventromedial PFC-amygdala FC with NA correlation was found in the depressed group than that in the never-depressed group. CONCLUSION This study confirms differential activity of the dorsal and ventral regions of the medial PFC in individuals with high neuroticism. Our findings suggest increased rostral medial PFC activity may be a marker of resilience to depression in the elderly and decreased anterior ventromedial PFC, PCC, and amygdala activity may be a result of successful emotion regulation in never-depressed higher NA individuals.