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Objective:Black adults are approximately twice as likely to develop Alzheimer’s disease (AD) than non-Hispanic Whites and access diagnostic services later in their illness. This dictates the need to develop assessments that are cost-effective, easily administered, and sensitive to preclinical stages of AD, such as mild cognitive impairment (MCI). Two computerized cognitive batteries, NIH Toolbox-Cognition and Cogstate Brief Battery, have been developed. However, utility of these measures for clinical characterization remains only partially determined. We sought to determine the convergent validity of these computerized measures in relation to consensus diagnosis in a sample of MCI and healthy controls (HC).Method:Participants were community-dwelling Black adults who completed the neuropsychological battery and other Uniform Data Set (UDS) forms from the AD centers program for consensus diagnosis (HC = 61; MCI = 43) and the NIH Toolbox-Cognition and Cogstate batteries. Discriminant function analysis was used to determine which cognitive tests best differentiated the groups.Results:NIH Toolbox crystallized measures, Oral Reading and Picture Vocabulary, were the most sensitive in identifying MCI apart from HC. Secondarily, deficits in memory and executive subtests were also predictive. UDS neuropsychological test analyses showed the expected pattern of memory and executive functioning tests differentiating MCI from HC.Conclusions:Contrary to expectation, NIH Toolbox crystallized abilities appeared preferentially sensitive to diagnostic group differences. This study highlights the importance of further research into the validity and clinical utility of computerized neuropsychological tests within ethnic minority populations.

Introduction The primary goal of subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) is to improve motor function. Dispositional optimism has been associated with better physical outcomes following a rehabilitation program in PD but has not been investigated in relation to STN-DBS. This study investigated the influence of dispositional optimism on motor outcomes following STN-DBS in individuals with PD. Methods A retrospective data analysis of 33 individuals with PD who underwent STN-DBS was conducted. Linear regression was used to determine whether dispositional optimism, measured by the Life Orientation Test-Revised questionnaire, predicted change in motor symptoms following DBS surgery, as assessed by the Movement Disorder Society-sponsored revision of the Unified PD Rating Scale, Part III. Self-reported levels of depressive and anxiety symptoms were included as co-variates. Results Higher pre-operative dispositional optimism combined with less self-reported depressive symptoms predicted greater post-operative improvement in motor symptoms from the baseline OFF-medication to post-operative ON-medication/ON-stimulation state, accounting for 38.8% of the variance in post-operative change. Conclusion The large percentage of variance in post-STN-DBS motor change predicted by pre-operative dispositional optimism and depressive symptoms suggests that assessment of these variables prior to surgery may provide valuable information for clinicians regarding the surgery's ultimate initial motor benefit for individuals with PD. If modifiable, these variables may provide cost-effective targets to improve motor outcomes of STN-DBS in PD.

Introduction Subthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson's disease (PD) but can worsen verbal fluency (VF). An optimal site of stimulation for overall motor improvement has been previously identified using an atlas-independent, fully individualized, field-modeling approach. This study examines if cardinal motor components (bradykinesia, tremor, and rigidity) share this identified optimal improvement site and if there is co-localization with a site that worsens VF. Methods An atlas-independent, field-modeling approach was used to identify sites of maximal STN DBS effect on overall and cardinal motor symptoms and VF in 60 patients. Anatomic coordinates were referenced to the STN midpoint. Symptom severity was assessed with the MDS-UPDRS part III and established VF scales. Results Sites for improved bradykinesia and rigidity co-localized with each other and the overall part III site (0.09 mm lateral, 0.93 mm posterior, 1.75 mm dorsal). The optimal site for tremor was posterior to this site (0.10 mm lateral, 1.40 mm posterior, 1.93 mm dorsal). Semantic and phonemic VF sites were indistinguishable and co-localized medial to the motor sites (0.32 mm medial, 1.18 mm posterior, 1.74 mm dorsal). Conclusion This study identifies statistically distinct, maximally effective stimulation sites for tremor improvement, VF worsening, and overall and other cardinal motor improvements in STN DBS. Current electrode sizes and voltage settings stimulate all of these sites simultaneously. However, future targeted lead placement and focused directional stimulation may avoid VF worsening while maintaining motor improvements in STN DBS.

Introduction Verbal fluency (VF) decline is a well-documented cognitive effect of Deep Brain Stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson's disease (PD). This decline may be associated with disruption to left-sided frontostriatal circuitry involving the anteroventral non-motor area of the STN. While recent studies have examined the impact of lead location in relation to functional STN subdivisions on VF outcomes, results have been mixed and methods have been limited by atlas-based location mapping. Methods Participants included 59 individuals with PD who underwent bilateral STN-DBS. Each participant's active contact location was determined in an atlas-independent fashion, relative to their individual MR-visualized STN midpoint. Multiple linear regression was used to examine lead location in each direction as a predictor of phonemic and semantic VF decline, controlling for demographic and disease variables. Results More anterior lead locations relative to the STN midpoint in the left hemisphere predicted greater phonemic VF decline (B = −2.34, B SE = 1.08, β = −0.29, sr2 = 0.08). Lead location was not a significant predictor of semantic VF decline. Conclusion Using an individualized atlas-independent approach, present findings suggest that more anterior stimulation of the left STN may uniquely contribute to post-DBS VF decline. This is consistent with models in which the anterior STN represents a “non-motor” functional subdivision with connections to frontal regions, e.g., the left dorsal prefrontal cortex. Future studies should investigate the effect of DBS lead trajectory on VF outcomes.

Background Caregiver burden (CB) in Parkinson's disease (PD) does not improve in the short term after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS), despite motor improvement. This may be due to increased caregiver demands after surgery or the possibility that DBS unresponsive non-motor factors, such as executive dysfunction, contribute to CB. Objective To evaluate the trajectory of CB in year 2 following bilateral STN DBS surgery for PD, and to test whether post-operative CB changes correlate with changes in executive function in a subgroup with available neuropsychological testing. Methods This retrospective analysis included 35 patients with PD whose caregivers completed the Caregiver Burden Inventory (CBI) at baseline and between 9 and 24 months after bilateral STN DBS. 14 of these patients had neuropsychological testing both at baseline and within 6 months of their follow up CBI assessment. Results CBI scores showed worsened CB from baseline to follow-up (16.4–21.5, p = 0.006). There was no correlation between change in executive function and change in CBI in the smaller subsample. Conclusion CB worsens in the 2 years after bilateral STN DBS despite improvement in motor symptoms and is not associated with change in executive dysfunction in the setting of advancing PD. These findings have implications on pre-operative counselling for patients and caregivers considering DBS for PD.

Major depressive disorder (MDD) is a common and burdensome mental health condition that is associated with significant occupational disability. Cognitive dysfunction, especially in neurocognitive domains of attention, memory, and executive functioning, is a well-recognized core feature of MDD that contributes to impairment in work functioning. Although there are many evidence-based treatments for MDD, neurocognitive deficits can persist even when other depressive symptoms are in remission after treatment. Despite the importance of cognition in mediating functional and occupational recovery, there has been little study of treatments that specifically address depression-associated cognitive dysfunction. In this chapter, we review the importance of cognitive dysfunction as it relates to workplace impairment in MDD, summarize the specific cognitive effects of evidence-based psychological and pharmacological treatments, and provide some principles to guide optimal treatment for working patients with MDD.

OBJECTIVE Cognitive outcomes in trials of postmenopausal hormone treatment have been inconsistent. Differing outcomes may be attributed to hormone formulation, treatment duration and timing, and differential cognitive domain effects. We previously demonstrated treatment benefits on visual cognitive function. In the present study, we describe the effects of hormone treatment on verbal outcomes in the same women, seeking to understand the effects of prior versus current hormone treatment on verbal function. METHODS This is a cross-sectional evaluation of 57 women (38 hormone users [25 prior long-term users and 13 current users] and 19 never-users). Hormone users took identical formulations of estrogen or estrogen + progestin (0.625 mg/d conjugated equine estrogens with or without medroxyprogesterone acetate) for at least 10 years, beginning within 2 years of menopause. Women were evaluated with tests of verbal function and functional magnetic resonance imaging (fMRI) of a verbal discrimination task. RESULTS All women scored similarly on assessments of verbal function (Hopkins Verbal Learning Test and a verbal discrimination task performed during the fMRI scanning session); however, women ever treated with hormones had more left inferior frontal (T = 3.72; P

Background: Clinical monitoring of patients with Parkinson’s disease (PD) for cognitive decline is an important element of care. The Montreal Cognitive Assessment (MoCA) has been proposed to be a sensitive tool for assessing cognitive impairment in PD. The aim of our study was to compare the responsiveness of the MoCA to decline in cognition to the responsiveness of the Mini Mental State Examination (MMSE) and the Scales for Outcomes of Parkinson’s disease-cognition (SCOPA-Cog). Methods: PD patients without dementia were enrolled at 6 North American movement disorders centers between 2008 and 2011. Participants received annual evaluations including the MoCA, MMSE, and SCOPA-Cog followed by formal neuropsychological testing. The gold standard for change in cognition was defined as the change on the neuropsychological test scores over the annual assessments. The Reliable Change Method was used to provide an estimate of the probability that a given difference score would be obtained by chance. The sensitivity of the MoCA, MMSE, and SCOPA-Cog to change was quantified using receiver operating characteristics (ROC) curves. Results: One hundred seventeen patients were included in the analysis. Participants were followed at mean intervals of 11 ± 2 months for a median of 2 (maximum 5) visits. According to the reliable change index, 56 intervals of cognitive testing showed a decline in global cognition. ROC analysis of change in MoCA, MMSE, and SCOPA-Cog global scores compared to gold standard testing found an area under the curve (AUC) of 0.55 (95% CI 0.48–0.62), 0.56 (0.48–0.63), and 0.63 (0.55–0.70) respectively. There were no significant differences in the AUCs across the tests. The sensitivity of the MoCA, MMSE, and SCOPA-Cog to change at various thresholds for decline in scores reached a maximum of 71% for a cut-off of 1 point change on the SCOPA-Cog. Conclusion: Using neuropsychological testing as a gold standard comparator, the performance of the MoCA, MMSE, and SCOPA-Cog for detecting decline in non-demented PD patients over a 1-year interval is poor. This has implications for clinical practice; stable scores may not be taken as reassurance of the absence of cognitive decline.

This retrospective study investigated the relationship between self-reports and caregiver perceptions of patients’ depressive symptoms and the respective ability of these reports to predict instrumental activities of daily living (IADLs) beyond what is accounted for by cognitive abilities in 71 patients with mild Alzheimer disease. Patients completed the Geriatric Depression Scale-Short Form, and caregivers completed the Behavior Rating Scale for Dementia assessing their perception of patients’ depressive symptoms. Caregivers also completed IADL items from the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory. Cognitive measures included the Mini-Mental State Examination, Logical Memory from the Wechsler Memory Scale III, and Trail Making Test, Part B. The relationship between self-reported depressive symptoms and caregiver report of patients’ depressive symptoms showed a trend toward significance ( r = .22, P = .06). Measures of depressive symptoms significantly predicted 12.5% of the variance in IADLs performance, beyond that accounted for by patient demographics and cognitive functioning. Interestingly, patients’ reports, rather than caregivers’, were particularly useful in this prediction.

Objective: The aim of this study was to examine the effects of an alertness-maintaining task (AMT) in older, fatigued drivers. Background: Fatigue during driving increases crash risk, and previous research suggests that alertness and driving in younger adults may be improved using a secondary AMT during boring, fatigue-eliciting drives. However, the potential impact of an AMT on driving has not been investigated in older drivers whose ability to complete dual tasks has been shown to decline and therefore may be negatively affected with an AMT in driving. Method: Younger ( n = 29) and older drivers ( n = 39) participated in a 50-minute simulated drive designed to induce fatigue, followed by four 10-minute sessions alternating between driving with and without an AMT. Results: Younger drivers were significantly more affected by fatigue on driving performance than were older drivers but benefitted significantly from the AMT. Older drivers did not demonstrate increased driver errors with fatigue, and driving did not deteriorate significantly during participation in the AMT condition, although their speed was significantly more variable with the AMT. Conclusion: Consistent with earlier research, an AMT applied during fatiguing driving is effective in improving alertness and reducing driving errors in younger drivers. Importantly, older drivers were relatively unaffected by fatigue, and use of an AMT did not detrimentally affect their driving performance. Application: These results support the potential use of an AMT as a new automotive technology to improve fatigue and promote driver safety, though the benefits of such technology may differ between different age groups.

Positive outcomes from intensive therapy for individuals with aphasia have been reported in the literature. Little is known about the characteristics of individuals who attend intensive comprehensive aphasia programs (ICAPs) and what factors may predict who makes clinically significant changes when attending such programs. Demographic data on participants from 6 ICAPs showed that individuals who attend these programs spanned the entire age range (from adolescence to late adulthood), but they generally tended to be middle-aged and predominantly male. Analysis of outcome data from 2 of these ICAPs found that age and gender were not significant predictors of improved outcome on measures of language ability or functional communication. However, time post onset was related to clinical improvement in functional communication as measured by the Communication Activities of Daily Living, second edition (CADL-2). In addition, for one sample, initial severity of aphasia was related to outcome on the Western Aphasia Battery-Revised, such that individuals with more severe aphasia tended to show greater recovery compared to those with mild aphasia. Initial severity of aphasia also was highly correlated with changes in CADL-2 scores. These results suggest that adults of all ages with aphasia in either the acute or chronic phase of recovery can continue to show positive improvements in language ability and functional communication with intensive treatment.

Just like their patients, physicians are susceptible to a variety of medical, neurological, and psychiatric conditions that have the potential to impair cognitive functioning which can lead to declines in patient care. Given the nature of the work environment, physicians are also at greater risk of problems related to stress and sleep deprivation, factors that can also impact cognition. Early recognition of potential problems on the part of the individual physician and the clinical institution is key. Having a model in place that triggers mechanisms for a comprehensive assessment of the problem, development of remediation or accommodation plans, and guidance throughout will maximize successful outcomes while protecting patient safety.

We examined the frequency of Parkinson disease with mild cognitive impairment (PD-MCI) and its subtypes and the accuracy of 3 cognitive scales for detecting PD-MCI using the new criteria for PD-MCI proposed by the Movement Disorders Society. Nondemented patients with Parkinson's disease completed a clinical visit with the 3 screening tests followed 1 to 3 weeks later by neuropsychological testing. Of 139 patients, 46 met Level 2 Task Force criteria for PD-MCI when impaired performance was based on comparisons with normative scores. Forty-two patients (93%) had multi-domain MCI. At the lowest cutoff levels that provided at least 80% sensitivity, specificity was 44% for the Montreal Cognitive Assessment and 33% for the Scales for Outcomes in Parkinson's Disease-Cognition. The Mini-Mental State Examination could not achieve 80% sensitivity at any cutoff score. At the highest cutoff levels that provided specificity of at least 80%, sensitivities were low (≤44%) for all tests. When decline from estimated premorbid levels was considered evidence of cognitive impairment, 110 of 139 patients were classified with PD-MCI, and 103 (94%) had multi-domain MCI. We observed dramatic differences in the proportion of patients who had PD-MCI using the new Level 2 criteria, depending on whether or not decline from premorbid level of intellectual function was considered. Recommendations for methods of operationalizing decline from premorbid levels constitute an unmet need. Among the 3 screening tests examined, none of the instruments provided good combined sensitivity and specificity for PD-MCI. Other tests recommended by the Task Force Level 1 criteria may represent better choices, and these should be the subject of future research.

Background/Aims: To assess the impact of mild cognitive impairment (MCI) or cognitive decline on health-related quality of life (HR-QOL) in Parkinson's disease (PD). Methods: HR-QOL measured by the Parkinson Disease Quality of Life Questionnaire (PDQ-39), MCI according to Movement Disorder Society Task Force criteria and cognitive decline from premorbid baseline were assessed in non-demented PD patients at 6 movement disorder clinics. Results: Among 137 patients, after adjusting for education, gender, disease duration, and Movement Disorder Society Unified Parkinson's Disease Rating Scale total score, MCI was associated with worse scores within the PDQ-39 dimension of communication (p = 0.008). Subjects were divided into tertiles of cognitive decline from premorbid level. Scores in the dimension of stigma were worst in the second tertile of cognitive decline (p = 0.03). MCI was associated with worse social support scores in the second tertile of cognitive decline (p = 0.008). Conclusion: MCI and cognitive decline from premorbid baseline are associated with reduced HR-QOL in communication, stigma, and social support domains. The cognitive decline from premorbid baseline modifies the association between MCI and HR-QOL in PD and knowing both will allow a better appreciation of difficulties patients face in daily life.

Disturbances of emotion regulation and depressive symptoms are common during the menopause transition. Reproductive hormone levels are not directly correlated with depressive symptoms, and other factors may influence mood symptoms during menopause. In this study, we sought to determine the role of metabolic function in mood symptoms during menopause, hypothesizing an association with menopause status and long-term glucose load. We studied 54 women across three menopause transition stages (15 premenopause, 11 perimenopause, and 28 postmenopause), examining effects of age, hormones, and metabolism on mood and neural activation during emotional discrimination. We assessed participants using behavioral and functional MRI measures of negative emotion and emotion discrimination, and glycated hemoglobin A1c, to assess long-term glucose load. We found that emotionally unpleasant images activated emotion regulation (amygdala) and cognitive association brain regions (prefrontal cortex, posterior cingulate, temporal-parietal-occipital (TPO) junction, hippocampus). Cognitive association region activity increased with menopause stage. Perimenopausal women had left TPO junction activation, and postmenopausal women had prefrontal cortex, posterior cingulate, and TPO junction activation. Negative affect was associated with decreased amygdala activation, while depression symptoms and negative mood were associated with increased TPO junction activation. Hemoglobin A1c was associated with negative interpretation bias of neutral images and cognitive region recruitment during emotion discrimination. FSH levels, indicating menopause stage, were associated with negative mood. Age was not associated with any behavioral measures or activation patterns during the emotion task. Our results suggest that an interaction between metabolic and hormonal factors may influence emotion regulation, leading to increased risk for depression during menopause.

Cognitive decline is prevalent in aging populations, and cognitive complaints are common during menopause. However, the extent of hormonal influence is unclear, particularly when considered independent of the aging process.We sought to determine differences in cognitive function attributable to menopause, hypothesizing that differences would be associated with reproductive rather than chronological age.In this cross-sectional study at a university hospital, we combined neuropsychological measures with functional magnetic resonance imaging to comprehensively assess cognitive function.Sixty-seven menopausal women, aged 42-61 yr, recruited from a population-based menopause study, grouped into menopause stages based on hormonal and cycle criteria (premenopause, perimenopause, and postmenopause), participated in the study.Neuropsychological and functional magnetic resonance imaging measures of verbal, visual, and executive cognitive function.We found age-independent menopause effects on verbal function. Menopause groups differed in phonemic verbal fluency (F = 3.58, P0.019) and regional brain activation (inferior frontal cortex: corrected P0.000 right, P0.036 left; left prefrontal cortex: P0.012); left temporal pole: P0.001). Verbal measures correlated with estradiol and FSH (phonemic fluency: R = 0.249, P0.047 estradiol, R = -0.275, P0.029 FSH; semantic fluency: R = 0.318, P0.011 estradiol, R = -0.321, P0.010 FSH; right inferior frontal cortex: R = 0.364, P0.008 FSH; left inferior frontal cortex: R = -0.431, P0.001 estradiol, left prefrontal cortex: R = 0.279, P0.045 FSH; left temporal pole: R = -0.310, P0.024 estradiol, R = 0.451, P0.001 FSH; left parahippocampal gyrus: R = -0.278, P0.044 estradiol; left parietal cortex: R = -0.326, P0.017 estradiol).Results suggest that verbal fluency mechanisms are vulnerable during the menopausal transition. Targeted intervention may preserve function of this critical cognitive domain.

We assessed the Pill Questionnaire as a screen for mild cognitive impairment in nondemented Parkinson's disease patients. The relationship between ability to remember medications for Parkinson's disease in the Pill Questionnaire, mild cognitive impairment, and deficits on neuropsychological tests performed 2-3 weeks later blind to Pill Questionnaire results was assessed in movement disorders clinic patients. In 109 subjects, inaccurate medication reporting on the Pill Questionnaire was associated with lower scores on the Montreal Cognitive Assessment, Scales for Outcomes in Parkinson's Disease-Cognition and with deficits in memory, attention, executive function-inhibitory control, processing speed, visuospatial function, and language. Inaccurate medication reporting was also associated with an adjusted odds ratio of 2.4 (95% CI, 0.91-5.88; P = .06) for mild cognitive impairment, with a specificity of 80% and sensitivity of 41%. The Pill Questionnaire is neither sensitive nor specific enough to be used as the sole screening or diagnostic tool for mild cognitive impairment. However, inaccurate medication reporting is associated with deficits spanning many cognitive domains and should alert a clinician to a higher likelihood of cognitive impairment.

Background: Caregivers of patients with mild cognitive impairment (MCI) need similar levels of support services as Alzheimer’s disease (AD) caregivers, but it is unclear if this translates to increased caregiver burden. Methods: 135 participants and their caregivers (40 MCI, 55 AD and 40 normal controls, NC) completed questionnaires, and the patients were administered neuropsychological tests. Results: The MCI caregivers reported significantly more overall caregiving burden than the NC, but less than the AD. They showed similar levels of emotional, physical and social burden as the AD caregivers. Among the MCI caregivers, the neuropsychiatric symptoms and executive functioning of the patients were related to a greater burden, and the caregivers with a greater burden reported lower life satisfaction and social support, and a greater need for support services. Conclusion: These results indicate that MCI caregivers are at increased risk for caregiver stress, and they require enhanced assistance and/or education in caring for their loved ones.

This pilot study describes a relationship between insulin resistance and μ-opioid neurotransmission in limbic appetite and mood-regulating regions in women with polycystic ovary syndrome (PCOS), suggesting that insulin-opioid interactions may contribute to behavioral and reproductive pathologies of PCOS. We found that [1] patients with PCOS who are insulin-resistant (n = 7) had greater limbic μ-opioid receptor availability (nondisplaceable binding potential) than controls (n = 5); [2] receptor availability was correlated with severity of insulin resistance; and [3] receptor availability normalized after insulin-regulating treatment.

Objective: The aim of this study was to evaluate the short-term stability and reliability of a brief computerized cognitive battery in established dementia types. Method: Patients were administered the computerized battery twice with administrations approximately 2 hours apart, with intervening conventional neuropsychological tests. Patients were classified clinically, via consensus conference, as healthy controls (n = 23), mild cognitive impairment (n = 20), Alzheimer’s disease (n = 52), dementia with Lewy Bodies ([DLB], n = 10), or frontotemporal dementia (n = 9). Results: Minimal practice effects were evident across Cog-State test administrations. Small magnitude improvements were seen across all groups on a working memory task, and healthy controls showed a mild practice effect on the accuracy of associative learning. Conclusions: In established dementia, administration of the CogState tasks appears sensitive to cognitive impairment in dementia. Repeat administration also provided acceptable stability and test-retest reliability with minimal practice effects at short test-retest intervals despite intervening cognitive challenges.

Objective To study the effects of combination hormone therapy (HT) on emotional processing in postmenopausal women with use of functional neuroimaging. Design A randomized, double-blind, placebo-controlled crossover study was performed. Setting A tertiary care university medical center. Participant(s) Ten healthy postmenopausal women (mean age 56.9 years, SD=1.4 years) were recruited. Intervention(s) Women were assigned randomly to the order they received combined HT, 5 μg ethinyl E 2 and 1 mg norethindrone acetate, and placebo. Volunteers received HT or placebo for 4 weeks, followed by a 1-month washout period, and then received the other treatment for 4 weeks. Subjects participated in a functional magnetic resonance imaging emotional processing task, where they were asked to rate emotional pictures as positive, negative, or neutral. Main Outcome Measure(s) Brain activation patterns were compared between HT and placebo conditions within subjects. Result(s) During negative emotional presentations, after subtracting the effect of neutral images, areas of significant differences between HT and placebo conditions were identified in the orbital, frontal, cingulate, and occipital cortices. During positive emotional image presentation there were significant differences between placebo and HT conditions within the medial frontal cortex. Conclusions Short-term menopausal treatment with combination HT affects regional brain activity within areas implicated in emotional processing.

Little is known about the service needs for persons caring for individuals with mild cognitive impairment (MCI). In this study, the level of support service need for caregivers of individuals diagnosed with Alzheimer disease (AD; N=55) and MCI (N=25) was compared with normal controls (N=44). Study partners (ie, caregivers) completed questionnaires about their service needs and participants' neurobehavioral symptoms, functional abilities, and frailty. Total, social, and mental health service needs were significantly different among the 3 groups (P

Objective: Limited research exists to explain differential executive functioning impairment in clinical populations, particularly between the Wisconsin Card Sorting Task (WCST) and the Trail Making Test (TMT). Methods: The distribution of clinical diagnoses was examined in patients failing none, one, or both tasks, and executive task performance was compared among dementia-related diagnoses. Two hundred and sixty-six participants received evaluations through an Alzheimer’s Disease Research Center, which included executive tasks. Dementia-related diagnoses were established through consensus. Results: Chi-square analyses indicated that TMT failure, with or without WCST failure, possessed higher associations with dementia diagnoses. Repeated measures analysis of variance similarly indicated that participants with dementia, especially mild and moderate severity, performed worse on TMT. Conclusions: Executive dysfunction was observed in dementia-related diagnoses, and TMT failure was implicated in dementia in higher proportions than WCST impairment. Trail Making Test appears more sensitive than WCST for assessing executive impairment across diagnoses, especially when time and resources are limited in screening and clinical settings.

Background A comprehensive, multidisciplinary screening process for deep brain stimulation (DBS) candidates is recommended, but is often time-consuming. Objective To determine the number of essential tremor (ET) referrals excluded from surgery and why, in order to develop recommendations for a minimum standard DBS evaluation process. Methods We reviewed the referrals of 100 consecutive potential DBS candidates with presumed ET at our center, identified reasons for excluding patients from DBS, and the point at which they dropped out of our evaluation process. Results Of the 100 tremor patients referred for DBS, 36 patients were approved for surgery. Patients were mainly excluded because of the movement disorders neurologist and neuropsychologist evaluations. Reasons included an inadequate medication trial (n = 20), incorrect diagnosis (n = 3), dementia (n = 3), and antagonistic interactions with the team (n = 1). 37 patients did not present, were uninterested or lost to follow-up. Neither neurosurgical evaluation nor brain imaging excluded candidates in this study, but are needed to proceed with DBS. Conclusions Our suggested minimum standard DBS screening process begins with a movement disorders neurologist and neuropsychologist evaluation in order to determine eligibility. Neurosurgical evaluation and brain imaging can then be performed if candidates are deemed eligible.

The effects of postmenopausal hormone treatment on cognitive outcomes are inconsistent in the literature. Emerging evidence suggests that cognitive effects are influenced by specific hormone formulations, and that progesterone is more likely to be associated with positive outcomes than synthetic progestin. There are very few studies of unopposed progesterone in postmenopausal women, and none that use functional neuroimaging, a sensitive measure of neurobiological function. In this study of 29 recently postmenopausal women, we used functional MRI and neuropsychological measures to separately assess the effects of estrogen or progesterone treatment on visual and verbal cognitive function. Women were randomized to receive 90 days of either estradiol or progesterone counterbalanced with placebo. After each treatment arm, women were given a battery of verbal and visual cognitive function and working memory tests, and underwent functional MRI including verbal processing and visual working memory tasks. We found that both estradiol and progesterone were associated with changes in activation patterns during verbal processing. Compared to placebo, women receiving estradiol treatment had greater activation in the left prefrontal cortex, a region associated with verbal processing and encoding. Progesterone was associated with changes in regional brain activation patterns during a visual memory task, with greater activation in the left prefrontal cortex and right hippocampus compared to placebo. Both treatments were associated with a statistically non-significant increase in number of words remembered following the verbal task performed during the fMRI scanning session, while only progesterone was associated with improved neuropsychological measures of verbal working memory compared to placebo. These results point to potential cognitive benefits of both estrogen and progesterone.

This study investigated whether healthy older adults with Mini-Mental State Examination (MMSE) scores above 23 exhibit cognitive impairment on neuropsychological tests. Participants completed the MMSE and a neuropsychological battery including tests of 10 domains. Results were compared to published normative data. On neuropsychological testing, participants performed well on measures of naming and recall but showed mild to moderate impairment in working memory and processing speed and marked impairment in inhibition, sustained attention, and executive functioning. Almost everyone (91%) scored at least 1 standard deviation (SD) below the mean in at least 1 domain. The median number of domains in which individuals scored below 1 SD was 3.0 of 10.0, whereas over 21% scored below 1 SD in 5 domains or more. With the strictest of definitions for impairment, 20% of this population scored below 2.0 SDs below the norm in at least 2 domains, a necessary condition for a diagnosis of dementia. The finding that cognitive impairment, particularly in attention and executive functioning, is found in healthy older persons who perform well on the MMSE has clinical and research implications in terms of emphasizing normal variability in performance and early identification of possible impairment.

We compared the relative utility of neuropsychological testing and positron emission tomography (PET) with [18F]fluorodeoxyglucose ([18F]FDG) in differentiating Alzheimer's disease (AD) from dementia with Lewy bodies (DLB). We studied 25 patients with AD, 20 with DLB, and 19 normal elderly controls. There was no difference between patient groups for MMSE, confrontational naming, or verbal learning. The DLB group was significantly more impaired than the AD group for verbal fluency, and the AD group was significantly more impaired than the DLB group for verbal delayed recall. The DLB group had greater difficulty than the AD group on a visual discrimination task that does not require motor functioning, but the difference did not reach significance. Family ratings of motor functioning suggested significantly greater impairment in DLB patients than in AD patients. PET studies revealed significantly lower local cerebral metabolic rates for glucose (lCMRglc) for visual cortex (Brodmann areas 17, 18, and 19) in the DLB than the AD group, but no differences for other regions commonly affected in AD, including posterior cingulate, superior parietal lobe, lateral temporal lobe, and the prefrontal region. Motor ratings were significantly correlated with lCMRglc in all areas of cerebral cortex, including Brodmann areas 17, 18, and 19. The results demonstrate a similar profile of cerebral hypometabolism in the two patient groups except in the visual cortex, where the DLB group shows markedly lower lCMRglc than the AD group. Neuropsychological testing also differentiates the groups, and family ratings of motor functioning are as robust as PET in these later stages of the disorders.

Amyotrophic lateral sclerosis (ALS) is a highly debilitating and rapidly fatal neurodegenerative disease. It has been suggested that social cognition may be affected, such as impairment in theory of mind (ToM) ability. Despite these findings, research in this area is scarce and the investigation of neural mechanisms behind such impairment is absent. Nineteen patients with ALS and eighteen healthy controls participated in this study. Because the mirror neuron system (MNS) is thought to be involved in theory of mind, we first implemented a straightforward action-execution and observation task to assess basic MNS function. Second, we examined the social-cognitive ability to understand actions of others, which is a component of ToM. We used fMRI to assess BOLD activity differences between groups during both experiments. Theory of mind was also measured behaviorally using the Reading the Mind in the Eyes test (RME). ALS patients displayed greater BOLD activity during the action-execution and observation task, especially throughout right anterior cortical regions. These areas included the right inferior operculum, premotor and primary motor regions, and left inferior parietal lobe. A conjunction analysis showed significantly more co-activated voxels during both the observation and action-execution conditions in the patient group throughout MNS regions. These results support a compensatory response in the MNS during action processing. In the action understanding experiment, healthy controls performed better behaviorally and subsequently recruited greater regions of activity throughout the prefrontal cortex and middle temporal gyrus. Lastly, action understanding performance was able to cluster patients with ALS into high and lower performing groups, which then differentiated RME performance. Collectively, these data suggest that social cognition, particularly theory of mind, may be affected in a subset of patients with ALS. This impairment may be related to functioning of the MNS and other regions related to action processing and understanding. Implications for future research are discussed.

This study examined the relationship between age and inhibitory functioning within a sample of older adults ranging in age from 60 to 85 years old. On the basis of earlier research, and confirmed by factor analysis, measures typically referred to as frontal lobe tasks were used as measures of inhibitory functioning. Findings demonstrated that inhibitory processes continued to decline with advancing age within the older sample. In addition, the role of inhibition in age-related performance deficits on a verbal list learning measure and an attention measure was examined. Hierarchical regression analyses showed that inhibition accounted for a significant proportion of the age-related variance on the two cognitive measures, whereas measures of reading speed accounted for a smaller proportion of the variance. In addition, when inhibition was first covaried out, reading speed no longer accounted for a significant proportion of the age-related variance. It is argued that inhibition is an important contributor to age-related performance decrements in cognition.

The mechanisms responsible for disordered reproductive, metabolic, appetite, and mood function in women with polycystic ovary syndrome (PCOS) are unclear. Increasing evidence suggests that changes in central opioid sensitivity in patients with PCOS contribute to the pathogenesis of the disease through mediation of insulin's neuromodulatory effects. This pilot study tested the hypothesis that interactions between central opioid activity and insulin resistance (IR) in limbic appetite and mood-regulating regions of women with PCOS may be associated with the behavioral and reproductive pathology of the disease. Central opioid activity was assessed by determining the availability of the μ-opioid receptor (μOR) for the opioid agonist β-endorphin. Positron emission tomography with a radioactive μOR-receptor selective radiotracer was used to compare receptor availability in women with IR-PCOS (n = 7) and with non-IR controls (n = 5), and also assessed the ability of the hypoglycemic agent, metformin, to restore μOR concentrations to normal levels. Before and after metformin treatment, the binding potential of the μOR was determined in IR-PCOS patients and controls. The data showed greater μOR availability in the limbic regions of IR-PCOS patients than non-IR controls. After 4 months of metformin treatment, receptor availability returned to levels found in the controls. The restoration of μOR binding capacity to control levels by metformin indicated that improved insulin sensitivity restored dysregulated opioid neurotransmission. The findings of this small pilot study suggest that insulin modulation of central opioid activity in PCOS may contribute to behavioral and reproductive pathologies of the disease.

Background: Little is known about caregiver burden in Parkinson disease (PD) patients undergoing brain stimulation (DBS) surgery. Objective: The aim of this exploratory analysis was to evaluate whether caregiver burden improves after bilateral subthalamic nucleus (STN) DBS for PD patients and identify baseline factors associated with caregiver burden. Methods: We analyzed the motor, cognitive and behavioral data of 12 PD patients (9 men/3 women) who underwent bilateral STN DBS and whose caregivers completed the Caregiver Burden Inventory (CBI) both before and approximately 6 months after bilateral STN DBS. Results: Total CBI score did not change from baseline (17.8 ± 10.7) to the 6 month evaluation (18.7 ± 13.1), despite a 29% improvement in the MDS-UPDRS motor score (baseline 40.3 ± 12.1 compared to 28.7 ± 8.4 at 6 months, p = 0.01). Change in total CBI score did not correlate with change in MDS-UPDRS Parts I–IV or MoCA from baseline to 6 months. In post-hoc analyses looking at baseline characteristics that may correlate with caregiver burden, only the disinhibition subscore on the Frontal Systems Behavioral Scale correlated positively with the baseline total CBI score (ρ = 0.763, p = 0.004). Conclusion: Caregiver burden for PD patients (as measured by the CBI) does not change 6 months after bilateral STN DBS, despite significant improvement in motor function. Only baseline behavioral problems, specifically disinhibition, correlated with higher baseline caregiver burden. Clinicians may need to better counsel patients on expectations for caregiver burden after DBS.

Aspects of performance on verbal list learning tasks, such as recall, recognition, and response bias, may vary with severity in Alzheimer's disease (AD). We administered a 10-item, single-category word list learning test using selective reminding procedures to 188 patients with probable AD and 36 healthy normal controls with equivalent age and education. We analyzed the total number of words recalled as well as discrimination and response bias indexes derived from signal detection theory. Recall and discrimination were impaired in patients with probable AD compared to controls, and recall scores were more sensitive to dementia severity than discrimination. While many AD patients showed a liberal response bias, their response bias varied considerably within patient groups and did not correlate with disease severity.

We examined the frequency of Parkinson disease with mild cognitive impairment (PD-MCI) and its subtypes and the accuracy of 3 cognitive scales for detecting PD-MCI using the new criteria for PD-MCI proposed by the Movement Disorders Society. Nondemented patients with Parkinson’s disease completed a clinical visit with the 3 screening tests followed 1 to 3 weeks later by neuropsychological testing. Of 139 patients, 46 met Level 2 Task Force criteria for PD-MCI when impaired performance was based on comparisons with normative scores. Forty-two patients (93%) had multi-domain MCI. At the lowest cutoff levels that provided at least 80% sensitivity, specificity was 44% for the Montreal Cognitive Assessment and 33% for the Scales for Outcomes in Parkinson’s Disease-Cognition. The Mini-Mental State Examination could not achieve 80% sensitivity at any cutoff score. At the highest cutoff levels that provided specificity of at least 80%, sensitivities were low (≤44%) for all tests. When decline from estimated premorbid levels was considered evidence of cognitive impairment, 110 of 139 patients were classified with PD-MCI, and 103 (94%) had multi-domain MCI. We observed dramatic differences in the proportion of patients who had PD-MCI using the new Level 2 criteria, depending on whether or not decline from premorbid level of intellectual function was considered. Recommendations for methods of operationalizing decline from premorbid levels constitute an unmet need. Among the 3 screening tests examined, none of the instruments provided good combined sensitivity and specificity for PD-MCI. Other tests recommended by the Task Force Level 1 criteria may represent better choices, and these should be the subject of future research.

While preliminary evidence supports the criterion validity of the CogState computerized brief battery in mild cognitive impairment (MCI) and Alzheimer disease (AD), definitive validation studies examining a wider range of dementia-related disorders relative to conventional neuropsychological techniques are necessary.Participants satisfying clinical consensus criteria for dementia (AD, n = 37; frontotemporal dementia, n = 7; and dementia with Lewy bodies, n = 5), MCI (n = 16), and the healthy controls (n = 22) were administered a battery of brief neuropsychological and select computerized (CogState) cognitive tests. The battery, administered through the University of Michigan Alzheimer's Disease Research Center, included measures of processing speed, attention, working memory, and learning.CogState and standard neuropsychological task scores were significantly lower for dementia participants than that of the nondementia groups (P.05), with a single CogState test distinguishing control from MCI participants, but minimal differentiation existing between dementias using the CogState. Correlations were modest between conventional and computerized test scores, covering matching domains and mostly reflecting the multidimensional nature of cognitive paradigms.Results support the clinical validity of this brief computerized screening battery when used in established dementias, but not to differentiate between various dementias, and suggest that the select CogState battery's effectiveness in identifying MCI from controls was not as strong as identifying specific dementias.

We assessed the Pill Questionnaire as a screen for mild cognitive impairment in nondemented Parkinson's disease patients. The relationship between ability to remember medications for Parkinson's disease in the Pill Questionnaire, mild cognitive impairment, and deficits on neuropsychological tests performed 2-3 weeks later blind to Pill Questionnaire results was assessed in movement disorders clinic patients. In 109 subjects, inaccurate medication reporting on the Pill Questionnaire was associated with lower scores on the Montreal Cognitive Assessment, Scales for Outcomes in Parkinson's Disease-Cognition and with deficits in memory, attention, executive function-inhibitory control, processing speed, visuospatial function, and language. Inaccurate medication reporting was also associated with an adjusted odds ratio of 2.4 (95% CI, 0.91-5.88; P = .06) for mild cognitive impairment, with a specificity of 80% and sensitivity of 41%. The Pill Questionnaire is neither sensitive nor specific enough to be used as the sole screening or diagnostic tool for mild cognitive impairment. However, inaccurate medication reporting is associated with deficits spanning many cognitive domains and should alert a clinician to a higher likelihood of cognitive impairment.

Background/Aims: The role of cognitive reserve in Parkinson’s disease (PD)-mild cognitive impairment (MCI) is incompletely understood. Methods: The relationships between PD-MCI, years of education, and estimated premorbid IQ were examined in 119 consecutive non-demented PD patients using logistic regression models. Results: Higher education and IQ were associated with reduced odds of PD-MCI in univariate analysis. In multivariable analysis, a higher IQ was associated with a significantly decreased odds of PD-MCI, but education was not. Conclusion: The association of higher IQ and decreased odds of PD-MCI supports a role for cognitive reserve in PD, but further studies are needed to clarify the interaction of IQ and education and the impact of other contributors such as employment and hobbies.

Background: Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) improves motor function in patients with medically intractable Parkinson’s disease (PD), but the effects of STN DBS on fatigue are unknown. The purpose of this study was to examine the effects of STN DBS on fatigue scores in patients with PD. Methods: Twenty PD patients underwent bilateral STN DBS surgery at our institution from 2007 to 2009. Onlydatafromthe17patientswhocompletedtheParkinsonFatigueScale(PFS)andUnifiedPDRatingScale (UPDRS) before and approximately 6 months after surgery were analyzed. Other evaluations included the Geriatric Depression Scale (GDS), Apathy Evaluation Scale (AES), and Epworth Sleepiness Scale (ESS). Results: When the cohort was analyzed as a whole, there was no significant change in the mean or binary PFS score from baseline to the 6 month evaluation. However, the fatigue response of individual subjects was variable. Six of 12 subjects with fatigue before surgery were not fatigued post-operatively, while 3/5 subjects without fatigue before surgery became fatigued after DBS surgery. Fatigue in 8 subjects remained unchanged. Change in fatigue scores correlated significantly with change in the motor UPDRS, GDS and AES. Improvement in PFS also correlated with a higher PFS baseline score and higher baseline UPDRS motor off score. Conclusions: Changes in fatigue severity were not observed in our cohort as a whole, but there were changes in fatigue on an individual level. These changes appear to be related to the effects of STN DBS on motor improvement and mood.

The role of ovarian hormones in maintaining neuronal integrity and cognitive function is still debated. This study was undertaken to clarify the potential relationship between postmenopausal hormone use and the cholinergic system.We hypothesized that early initiated hormone therapy (HT) preserves the cholinergic system and that estrogen therapy (ET) would be associated with higher levels of acetylcholinesterase activity in the posterior cingulate cortex and hippocampus compared to estrogen plus progestin therapy (EPT) or no HT.We conducted a cross-sectional study at a university teaching hospital.Fifty postmenopausal women (age, 65.2 ± 0.7 yr) with early long-term HT (n = 34; 13 ET and 21 EPT) or no HT (n = 16) participated in the study.There were no interventions.We measured cholinergic activity (acetylcholinesterase) in the hippocampus and posterior cingulate brain regions as measured by N-[(11)C]methylpiperidin-4-yl propionate and positron emission tomography as a marker of cholinergic function.Significant effects of treatment on cholinergic activity measures were obtained in the left hippocampus (F = 3.56; P = 0.04), right hippocampus (F = 3.42; P = 0.04), and posterior cingulate (F = 3.76; P = 0.03). No significant effects were observed in a cortical control region. Post hoc testing identified greater cholinergic activity in the EPT group compared to the no-HT group in the left hippocampus (P = 0.048) and posterior cingulate (P = 0.045), with a nonstatistically significant trend in the right hippocampus (P = 0.073).A differential effect of postmenopausal ET and EPT on cholinergic neuronal integrity was identified in postmenopausal women. The findings are consistent with a preservation of cholinergic neuronal integrity in the EPT group.