Predictors of Cognitive Change in Parkinson Disease: A 2-year Follow-up Study.

BACKGROUND: Mild cognitive impairment is common in Parkinson disease (PD-MCI). However, instability in this clinical diagnosis and variability in rates of progression to dementia raises questions regarding its utility for longitudinal tracking and prediction of cognitive change in PD. We examined baseline neuropsychological test and cognitive diagnosis predictors of cognitive change in PD. METHODS: Persons with PD, without dementia PD (N=138) underwent comprehensive neuropsychological assessment at baseline and were followed up to 2 years. Level II Movement Disorder Society criteria for PD-MCI and PD dementia (PDD) were applied annually. Composite global and domain cognitive z -scores were calculated based on a 10-test neuropsychological battery. RESULTS: Baseline diagnosis of PD-MCI was not associated with a change in global cognitive z -scores. Lower baseline attention and higher executive domain z -scores were associated with greater global cognitive z -score worsening regardless of cognitive diagnosis. Worse baseline domain z -scores in the attention and language domains were associated with progression to MCI or PDD, whereas higher baseline scores in all cognitive domains except executive function were associated with clinical and psychometric reversion to "normal" cognition. CONCLUSIONS: Lower scores on cognitive tests of attention were predictive of worse global cognition over 2 years of follow-up in PD, and lower baseline attention and language scores were associated with progression to MCI or PDD. However, PD-MCI diagnosis per se was not predictive of cognitive decline over 2 years. The association between higher executive domain z -scores and greater global cognitive worsening is probably a spurious result.

Perceived social support declines after deep brain stimulation surgery in patients with Parkinson's disease.

INTRODUCTION: The Social Provisions Scale (SPS) measures a person's perceived social support. We evaluated the perceived social support in Parkinson's disease (PD) patients before and after subthalamic nucleus (STN) deep brain stimulation (DBS) and its impact on clinical outcomes following DBS. METHODS: We analyzed 55 PD patients who underwent STN DBS surgery and completed the SPS, PDQ-39, and MDS-UPDRS Parts I-IV before and 6-12 months after surgery. Some patients also completed global cognitive, mood and apathy scales. Caregivers completed the CBI at each visit. Linear regression models and linear mixed models evaluated the association between the SPS baseline score, MDS-UPDRS and PDQ-39 scores, the association between MDS-UPDRS, CBI and the SPS follow-up score, and the association between SPS, global cognition and other psychological variables. RESULTS: DBS implantation improved MDS-UPDRS I-IV and PDQ-39 scores. Perceived social support declined after DBS (baseline SPS total 82.55 ± 7.52 vs. follow-up SPS total 78.83 ± 9.02, p = 0.0001). Baseline SPS total score was not significantly associated with the MDS-UPDRS or PDQ-39 scores at follow-up. MDS-UPDRS scores and the CBI at follow-up had no significant association with SPS total score at follow-up. Measures of global cognition, mood and apathy were associated with the SPS before and after DBS, and the association was independent of STN DBS. CONCLUSION: After STN DBS, PD patients experienced a decrease in perceived social support, but baseline perceived social support did not impact clinical outcomes. It is important to further identify factors that may contribute to this perception of worsened social support.

Decline of verbal fluency with lateral superior frontal gyrus penetration in subthalamic nucleus deep brain stimulation for Parkinson disease.

OBJECTIVE: Verbal fluency (VF) decline is a well-recognized adverse cognitive outcome following subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinson disease (PD). The mechanisms underlying VF decline, whether from stimulation, lesioning, or both, remain unclear. This study aims to investigate the unique effects of DBS lead trajectory on VF beyond previously reported effects of active contact location. METHODS: The study population included 56 patients with idiopathic PD who underwent bilateral STN DBS. Phonemic and semantic VF scores were compared pre- and postoperatively. Features of the electrode trajectory were measured on postoperative imaging, including distance from the falx cerebri, distance from the superior frontal sulcus, and caudate nucleus penetration. The authors used t-tests, Pearson's correlation, and multiple linear regression analyses to examine the relationship between VF change and demographic, disease, and electrode trajectory variables. RESULTS: The laterality of entry within the left superior frontal gyrus (SFG) predicted greater phonemic VF decline (sr2 = 0.28, p < 0.001) after controlling for active contact location. VF change did not differ by the presence of caudate nucleus penetration in either hemisphere (p > 0.05). CONCLUSIONS: Lateral penetration of the SFG in the left hemisphere is associated with worsening phonemic VF and has greater explanatory power than active contact location. This may be explained by lesioning of the lateral SFG-Broca area pathway, which is implicated in language function.

Laptop-Administered NIH Toolbox and Cogstate Brief Battery in Community-Dwelling Black Adults: Unexpected Pattern of Cognitive Performance between MCI and Healthy Controls.

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.

Anterior lead location predicts verbal fluency decline following STN-DBS in Parkinson's disease.

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, ß = -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.

The impact of dispositional optimism and depression on post-operative motor functioning following deep brain stimulation surgery for Parkinson's disease.

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.

Localization of motor and verbal fluency effects in subthalamic DBS for Parkinson's disease.

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.

Parkinson disease with mild cognitive impairment: Domain-specific cognitive complaints predict dementia.

BACKGROUND: The presence of subjective cognitive complaints (SCC) as a predictor of cognitive impairment in Parkinson´s disease (PD) has shown conflicting results. Most previous studies only assessed complaints in the memory domain. We investigate the association of SCCs across cognitive domains with development of mild cognitive impairment (PD-MCI) and dementia (PDD) in PD and to assess agreement between SCCs and objective cognitive impairments in this population. METHODS: This is a retrospective analysis of a prospective cohort study. Participants were enrolled at six North-American movement disorders centers. They underwent neuropsychological and non-cognitive clinical evaluations, including the modified Neurobehavioral Inventory to elicit SCC (rated by each patient and independently by their close contact (CC)). Associations between SCCs and development of future cognitive impairment were assessed. Agreement between SCCs and objective impairment within the same domain was also calculated. RESULTS: Of 138 included PD patients, 42% fulfilled criteria for PD-MCI. None of the NBI items predicted development of cognitive impairment after one and two years in PD with normal cognition. In PD-MCI patients, SCCs related to attention predicted dementia at year one. CC ratings of SCCs related to memory and language problems predicted PDD in PD-MCI patients. According to CC reported patients' complaints, there was a significant agreement between SCCs and objective cognitive test scores on attention. CONCLUSIONS: Eliciting SCCs including cognitive domains other than memory is crucial for a complete evaluation, including both patient and CC report. Memory, language, and especially attention SCCs in PD-MCI may predict progression to dementia.

Caregiver burden worsens in the second year after subthalamic nucleus deep brain stimulation for Parkinson's disease.

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.

Responsiveness to Change of the Montreal Cognitive Assessment, Mini-Mental State Examination, and SCOPA-Cog in Non-Demented Patients with Parkinson's Disease.

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.

Postmenopausal hormone treatment alters neural pathways but does not improve verbal cognitive function.

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 < 0.001) and right prefrontal cortex (T = 3.53; P < 0.001) activation during the verbal task. Hormone-treated women performed slightly worse on the verbal discrimination task (mean accuracy 81.72 ±â€Š11.57 ever-treated, 85.30 ±â€Š5.87 never-treated, P = 0.14), took longer to respond (mean reaction time 1.10 ±â€Š0.17 s ever-treated, 1.02 ±â€Š0.11 never-treated, P = 0.03), and remembered fewer previously viewed words (mean accuracy 62.21 ±â€Š8.73 ever-treated, 65.45 ±â€Š7.49 never-treated, P = 0.18). Increased posterior cingulate activity was associated with longer response times (R = 0.323, P = 0.015) and worse delayed verbal recall (R = -0.328, P = 0.048), suggesting that increased activation was associated with less efficient cognitive processing. We did not detect between group differences in activation in the left prefrontal cortex, superior frontal cortex, thalamus, or occipital/parietal junction. CONCLUSIONS: Although current and past hormone treatment was associated with differences in neural pathways used during verbal discrimination, verbal function was not higher than never-users.

Fatigue in Younger and Older Drivers: Effectiveness of an Alertness-Maintaining Task.

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.

Forbidden word entropy of cerebral oximetric values predicts postoperative neurocognitive decline in patients undergoing aortic arch surgery under deep hypothermic circulatory arrest.

PURPOSE: Up to 53% of cardiac surgery patients experience postoperative neurocognitive decline. Cerebral oximetry is designed to detect changes in cerebral tissue saturation and therefore may be useful to predict which patients are at risk of developing neurocognitive decline. METHODS: This is a retrospective analysis of a prospective study originally designed to determine if treatment of cerebral oximetry desaturation is associated with improvement in postoperative cognitive dysfunction in patients undergoing aortic reconstruction under deep hypothermic circulatory arrest. Cognitive function was measured, preoperatively and 3 months postoperatively, with 15 neuropsychologic tests administered by a psychologist; the individual test scores were summed and normalized. Bilateral cerebral oximetry data were stored and analyzed using measures of entropy. Cognitive decline was defined as any decrease in the summed normalized score from baseline to 3 months. RESULTS: Seven of 17 (41%) patients suffered cognitive decline. There was no association between baseline cerebral oximetry and postoperative cognitive dysfunction. Nor were changes in oximetry values associated with cognitive decline. However, cognitive decline was associated with loss of forbidden word entropy (FwEn) (correlation: Rho ρ = 0.51, P = 0.037 for left cerebral oximetry FwEn and ρ = 0.54, P = 0.025 for right cerebral oximetry FwEn). CONCLUSION: Postoperative cognitive decline was associated with loss of complexity of the time series as shown by a decrease in FwEn from beginning to end of the case. This suggests that regulation of cerebral oximetry is different between those who do and those who do not develop cognitive decline.

Metabolic and hormone influences on emotion processing during menopause.

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.

A suggested minimum standard deep brain stimulation evaluation for essential tremor.

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.

Cognitive Deficits in Healthy Elderly Population With "Normal" Scores on the Mini-Mental State Examination.

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.

Diagnostic Profiles of Patients Differentially Failing Executive Functioning Measures.

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.

Patient Mood and Instrumental Activities of Daily Living in Alzheimer Disease: Relationship Between Patient and Caregiver Reports.

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.

Distinct cognitive effects of estrogen and progesterone in menopausal women.

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.

Action processing and mirror neuron function in patients with amyotrophic lateral sclerosis: an fMRI study.

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.