Cortical oscillatory dysfunction in Parkinson disease during movement activation and inhibition.

Response activation and inhibition are functions fundamental to executive control that are disrupted in Parkinson disease (PD). We used magnetoencephalography to examine event related changes in oscillatory power amplitude, peak latency and frequency in cortical networks subserving these functions and identified abnormalities associated with PD. Participants (N = 18 PD, 18 control) performed a cue/target task that required initiation of an un-cued movement (activation) or inhibition of a cued movement. Reaction times were variable but similar across groups. Task related responses in gamma, alpha, and beta power were found across cortical networks including motor cortex, supplementary and pre- supplementary motor cortex, posterior parietal cortex, prefrontal cortex and anterior cingulate. PD-related changes in power and latency were noted most frequently in the beta band, however, abnormal power and delayed peak latency in the alpha band in the pre-supplementary motor area was suggestive of a compensatory mechanism. PD peak power was delayed in pre-supplementary motor area, motor cortex, and medial frontal gyrus only for activation, which is consistent with deficits in un-cued (as opposed to cued) movement initiation characteristic of PD.

The Relationship Between Maladaptive Personality and Social Role Impairment in Depressed Older Adults in Primary Care.

Objective: Personality pathology is associated with impaired social functioning in adults, though further evidence is needed to examine the individual contributions of personality traits and processes to social functioning in depressed older adults. This study is a secondary analysis examining the relationship between maladaptive personality traits and processes and social role impairment in depressed older adults in primary care. Methods: Participants (N = 56) were 77% female and ranged in age between 55-89 (M = 66.82, SD = 8.75). Personality pathology was measured by maladaptive traits (NEO-FFI) and processes (Inventory of Interpersonal Problems; IIP-PD-15). Individual variable as well as combined predictive models of social role impairment were examined. Results: Higher neuroticism (ß = 0.30, p < .05), lower agreeableness (ß = -0.35 p < .001) and higher IIP-PD-15 (ß = 0.28, p < .01) scores predicted greater impairment in social role functioning. A combined predictive model of neuroticism and IIP-PD-15 scores predicted unique variance in social role impairment (R2 = .71). Conclusion: These results link select personality traits and interpersonal processes to social role impairment, suggesting that these are indicators of personality pathology in older adults. Clinical Implications: These findings lend preliminary support for clinical screening of personality pathology in depressed older adults utilizing both personality trait and process measures.

Sex specific cognitive differences in Parkinson disease.

Parkinson disease (PD) is a progressive neurodegenerative disorder that is 1.5 times more common in males than in females. While motor progression tends to be more aggressive in males, little is known about sex difference in cognitive progression. We tested the hypothesis that there are sex differences in cognitive dysfunction in non-demented PD. We evaluated 84 participants (38 females) with PD and 59 controls (27 females) for demographic variables and cognitive function, including attention, working memory, executive function, and processing speed. Multivariate ANOVA revealed no significant differences between groups for demographic variables, including age, years of education, global cogntition, daytime sleepiness, predicted premorbid IQ, UPDRS score, PD phenotype, or disease duration. For cognitive variables, we found poorer performance in males versus females with PD for measures of executive function and processing speed, but no difference between male and female controls. Specifically, PD males showed greater deficits in Verbal Fluency (category fluency, category switching, and category switching accuracy), Color Word Interference (inhibition), and speed of processing (SDMT). There were no differences in measures of working memory or attention across sex and inconsistent findings for switching. Our data indicate that males with PD have significantly greater executive and processing speed impairments compared to females despite no differences in demographic variables or other measures of disease severity. Our findings are consistent with the steeper slope of disease progression reported in males with PD.

MRI-guided laser interstitial thermal thalamotomy for medically intractable tremor disorders.

INTRODUCTION: Medically intractable tremors are a common, difficult clinical situation. Deep brain stimulation decreases Parkinson's disease resting tremor and essential tremor, but not all patients are candidates from a diagnostic, medical, or social standpoint, prompting the need for alternative surgical strategies. METHODS: We describe 13 patients with medically intractable tremor treated with laser interstitial thermal thalamotomy performed under general anesthesia using live MRI-guidance and the Clearpoint stereotactic system. RESULTS: All patients had a dramatic decrease in tremor immediately postoperatively, which has been sustained through follow-up (3-17 months) in all but 1 patient (mean tremor score reduction of 62%; 10.33 ± 2.69 to 3.89 ± 3.1). Objective side effects were transient and included imbalance and paresthesia. CONCLUSION: Medically intractable tremor treated with laser interstitial thermal thalamotomy may be a useful addition to the treatment armamentarium for medically intractable tremor disorders. © 2018 International Parkinson and Movement Disorder Society.

Altered Cortico-Limbic Network Connectivity in Parkinsonian Depression: The Effect of Antidepressants.

BACKGROUND: Depression is a common comorbidity of Parkinson's disease (PD); however, the impact of antidepressant status on cortical function in parkinsonian depression is not fully understood. While studies of resting state functional MRI in major depression have shown that antidepressant treatment affects cortical connectivity, data on connectivity and antidepressant status in PD is sparse. OBJECTIVE: We tested the hypothesis that cortico-limbic network (CLN) resting state connectivity is abnormal in antidepressant-treated parkinsonian depression. METHODS: Thirteen antidepressant-treated depressed PD and 47 non-depressed PD participants from the Parkinson's Progression Markers Initiative (PPMI) database were included. Data was collected using 3T Siemens TIM Trio MR scanners and analyzed using SPM and CONN functional connectivity toolbox. Volumetric analysis was also performed using BrainSuite. RESULTS: We found decreased connectivity in the antidepressant-treated depressed PD group when compared to non-depressed PD between the left frontal operculum and bilateral insula, and also reduced connectivity between right orbitofrontal cortex and left temporal fusiform structures. Increased depression scores were associated with decreased insular-frontal opercular connectivity. No ROI volumetric differences were found between groups. CONCLUSION: Given the relationship between depression scores and cortico-limbic connectivity in PD, the abnormal insular-frontal opercular hypoconnectivity in this cohort may be associated with persistent depressive symptoms or antidepressant effects.

Psychotherapy Termination Practices with Older Adults: Impact of Patient and Therapist Characteristics.

OBJECTIVES: The aims of this study were to survey clinicians' opinions regarding psychotherapy practices in mutual termination with a specified population (depressed older adult outpatients) and to examine the patient and therapist characteristics that may influence such practices. METHODS: We surveyed psychologists' (N = 96) psychotherapy termination practices, using a hypothetical depressed older adult as a referent, to assess consensus on the appropriateness of various guidelines to termination and to examine whether these differ as a function of patient and therapist characteristics. RESULTS: Several practices were generally agreed to be "extremely appropriate" when terminating psychotherapy with older adults, including collaborating to determine the end date of treatment and discussing patient growth. Data also indicate that patient factors, such as personality pathology, and therapist factors, such as having an Integrative theoretical orientation were associated with differential endorsement of termination practices. Identification as a geropsychologist or working regularly with older adults were associated with a more cautious approach to termination. CONCLUSIONS: There is substantial consensus regarding many approaches to termination, but modifications might be appropriate depending on patient characteristics. CLINICAL IMPLICATIONS: Clinicians agree on a set of fundamental termination practices when working with older adults, but modify these based on orientation and diagnosis.

Longer Duration of MAO-B Inhibitor Exposure is Associated with Less Clinical Decline in Parkinson's Disease: An Analysis of NET-PD LS1.

BACKGROUND: Monoamine oxidase type B (MAO-B) inhibitors exhibit neuroprotective effects in preclinical models of PD but clinical trials have failed to convincingly demonstrate disease modifying benefits in PD patients. OBJECTIVE: To perform a secondary analysis of NET-PD LS1 to determine if longer duration of MAO-B inhibitor exposure was associated with less clinical decline. METHODS: The primary outcome measure was the Global Outcome (GO), comprised of 5 measures: change from baseline in the Schwab and England (ADL) scale, the 39-item Parkinson's Disease Questionnaire (PDQ-39), the UPDRS Ambulatory Capacity Scale, the Symbol Digit Modalities Test, and the most recent Modified Rankin Scale. A linear mixed model was used to explore the association between the cumulative duration of MAO-B inhibitor exposure and the GO, adjusting for necessary factors and confounders. Associations between MAO-B inhibitor exposure and each of the five GO components were then studied individually. RESULTS: 1616 participants comprised the analytic sample. Mean observation was 4.1 (SD = 1.4) years, and 784 (48.5%) participants received an MAO-B inhibitor. The regression coefficient of cumulative duration of MAO-B inhibitor exposure (in years) on the GO was - 0.0064 (SE = 0.002, p = 0.001). Significant associations between duration of MAO-B inhibitor exposure and less progression were observed for ADL (p < 0.001), Ambulatory Capacity (p < 0.001), and the Rankin (p = 0.002). CONCLUSIONS: Our analysis identified a significant association between longer duration of MAO-B inhibitor exposure and less clinical decline. These findings support the possibility that MAO-B inhibitors slow clinical disease progression and suggest that a definitive prospective trial should be considered.

Cognitive and Psychiatric Disturbances in Parkinsonian Syndromes.

Parkinsonian syndromes share clinical signs including akinesia/bradykinesia and rigidity, which are consequences of pathology involving dopaminergic substantia nigra neurons. Yet cognitive and psychiatric disturbances are common, even early in the course of disease. Executive dysfunction is often measurable in newly diagnosed Parkinson's disease. Treatment with dopaminergic medications, particularly dopamine agonists, has been associated with hallucinations and impulse control disorder. Older age, presence of APOE-4 gene, and/or other factors result in amyloid plaque deposition that, in turn, accelerates cortical Lewy body plus tau pathology, linking Dementia with Lewy Bodies and Parkinson's disease with early dementia with Alzheimer's disease. Treatments available for cognitive deficits, depression, and psychotic symptoms are discussed.

Positive attitude toward life, emotional expression, self-rated health, and depressive symptoms among centenarians and near-centenarians.

OBJECTIVES: Favorable attitudes, emotions, personality characteristics, and self-rated health have been associated with successful aging in late life. However, less is known regarding these constructs and their relationships to mental health outcomes in the oldest old persons. This study examined cross-sectional relationships of these psychological factors to depressive symptoms in centenarians and near-centenarians. METHODS: A selected sample of Ashkenazi Jewish older adults aged 98-107 (n = 54, 78% female) without significant cognitive impairment participated. Cognitive function was assessed by Mini-Mental Status Examination, positive attitude toward life and emotional expression by the Personality Outlook Profile Scale (POPS), self-rated health by participants' subjective rating of their present health, and depressive symptoms by the Geriatric Depression Scale. RESULTS: Results demonstrated inverse associations of the positive attitude toward life domain of the POPS and self-rated health with participants' levels of depressive symptoms even after adjusting for the effects of history of medical illnesses, cognitive function, and demographic variables. Additionally, participants with high levels of care showed higher levels of depressive symptoms. Path analysis supported the partially mediating role of positive attitude toward life in the relationship between self-rated health and depressive symptoms. CONCLUSION: These findings emphasized the important roles of positive attitudes and emotions as well as self-rated health in mental health outcomes in the oldest old. Although, limited by its cross-sectional design, findings suggest these psychological factors may exert protective effects on mental health outcomes in advanced age.

Sex Differences in Clinical Features of Early, Treated Parkinson's Disease.

INTRODUCTION: To improve our understanding of sex differences in the clinical characteristics of Parkinson's Disease, we sought to examine differences in the clinical features and disease severity of men and women with early treated Parkinson's Disease (PD) enrolled in a large-scale clinical trial. METHODS: Analysis was performed of baseline data from the National Institutes of Health Exploratory Trials in Parkinson's Disease (NET-PD) Long-term Study-1, a randomized, multi-center, double-blind, placebo-controlled study of 10 grams of oral creatine/day in individuals with early, treated PD. We compared mean age at symptom onset, age at PD diagnosis, and age at randomization between men and women using t-test statistics. Sex differences in clinical features were evaluated, including: symptoms at diagnosis (motor) and symptoms at randomization (motor, non-motor, and daily functioning). RESULTS: 1,741 participants were enrolled (62.5% male). No differences were detected in mean age at PD onset, age at PD diagnosis, age at randomization, motor symptoms, or daily functioning between men and women. Differences in non-motor symptoms were observed, with women demonstrating better performance compared to men on SCOPA-COG (Z = 5.064, p<0.0001) and Symbol Digit Modality measures (Z = 5.221, p<0.0001). CONCLUSIONS: Overall, men and women did not demonstrate differences in clinical motor features early in the course of PD. However, the differences observed in non-motor cognitive symptoms suggests further assessment of the influence of sex on non-motor symptoms in later stages of PD is warranted.

Parkinson's disease severity and use of dopaminergic medications.

BACKGROUND: The effects of dopaminergic therapy in parkinson's disease (PD) can vary depending on the class of medication selected. OBJECTIVE: The aim of this post hoc study was to determine if the class of dopaminergic therapy correlated with disease severity in persons with early, treated PD. METHODS: A non-parametric global statistical test (GST) was used to assess the status of participants treated with dopamine agonist (DA) monotherapy, levodopa (LD) monotherapy or combined LD and DA therapy on multiple PD outcomes encompassing motor, cognitive, psychiatric and autonomic function, as well as disability and quality of life. RESULTS: The outcomes measured at the beginning of the study showed lower disease burden for participants on initial DA monotherapy compared to those taking combined LD and DA therapy after controlling for age, education, taking cog-meds and amantadine. CONCLUSION: This observation suggests that clinicians treating early PD patients favor combined LD and DA therapy in patients with more disabling features over DA monotherapy. As such, studies of PD progression in treated PD patients may be affected by the class of symptomatic dopaminergic therapy.

Personality, self-rated health, and cognition in centenarians: do personality and self-rated health relate to cognitive function in advanced age?

Personality and self-rated health have been linked previously to cognitive outcome in late life. However, these associations have not been shown among the oldest old. This study examined relationships between personality, self-rated health, and cognitive function in a selected sample of Ashkenazi Jewish centenarians (n=68, 59% female) aged 95 to 106 who lived independently in the community. Personality was measured using the Personality Outlook Profile Scale (POPS), a brief measure that was validated in this population. Self-rated health was assessed by participants' subjective rating of their present health, and Mini-Mental Status Examination was used to determine cognitive function. Results showed positive associations of the Positive Attitude Towards Life domain of the POPS and self-rated health with participants' current cognitive function. These associations remained significant even after adjusting for the effects of participants'age, gender, marital status, education, and history of medical illnesses. Further exploratory analysis using structural equations modeling showed significant associations among the three variables, but demonstrated a borderline significant level of mediating effect of personality on the relationship between self-rated health and cognition. These results reemphasized the independent roles of personality and self-rated health on centenarians' cognitive outcomes. Future studies will further elucidate the impact of personality and self-rated health on cognitive outcomes in the oldest old.

Positive attitude towards life and emotional expression as personality phenotypes for centenarians.

Centenarians have been reported to share particular personality traits including low neuroticism and high extraversion and conscientiousness. Since these traits have moderate to high heritability and are associated with various health outcomes, personality appears linked to bio-genetic mechanisms which may contribute to exceptional longevity. Therefore, the present study sought to detect genetically-based personality phenotypes in a genetically homogeneous sample of centenarians through developing and examining psychometric properties of a brief measure of the personality of centenarians, the Personality Outlook Profile Scale (POPS). The results generated two personality characteristics/domains, Positive Attitude Towards Life (PATL: optimism, easygoing, laughter, and introversion/outgoing) and Emotional Expression (EE: expressing emotions openly and not bottling up emotions). These domains demonstrated acceptable concurrent validity with two established personality measures, the NEO-Five Factor Inventory and Life Orientation Test-Revised. Additionally, centenarians in both groups had lower neuroticism and higher conscientiousness than the US adult population. Findings suggest that the POPS is a psychometrically sound measure of personality in centenarians and capture personality aspects of extraversion, neuroticism, and conscientiousness, as well as dispositional optimism which may contribute to successful aging.

Health and social adjustment of homeless older adults with a mental illness.

OBJECTIVE: To better inform treatment strategies, this study compared mental health, substance use, physical health, and social support among young, middle-aged, and older homeless adults before and after participation in intensive case management services. METHODS: Data were obtained from the Access to Community Care and Effective Services and Supports (ACCESS) public database. Young (age 18 to 34; N=2,469), middle-aged (age 35 to 54; N=4,358), and older (age 55 or older; N=408) homeless adults with a mental illness were compared on the basis of demographic characteristics and measures of substance use, mental and general medical health, and social support at baseline by using Kruskal-Wallis and chi square tests and at three-month and 12-month follow-ups by using mixed-model analysis. RESULTS: Older adults had fewer severe mental health and substance abuse problems than the two groups of younger adults at baseline. At 12-month follow-up, all age groups had improvements in housing, substance use, and psychiatric symptoms, but rates of psychiatric symptoms had improved the most among young adults, and their scores for psychiatric symptoms were the lowest on average of any group. Compared with older adults, adults in the younger groups showed greater decreases in substance use. CONCLUSIONS: Older homeless adults appeared to follow a different treatment trajectory than their younger counterparts, possibly because of lower severity of mental illness at baseline, and may need specific interventions to address their unique pathways to homelessness.

Learning From The Past and Planning For The Future: The Challenges Of And Solutions For Integrating Aging Into Doctoral Psychology Training.

The long forecast "elder boom" has begun. Beginning in 2011, ten thousand members of the "baby boom" generation began turning 65 each day. This demographic shift in our society mandates that pre-doctoral programs in clinical psychology incorporate aging as an integral component of their core and elective training. While fully supporting the concept of broad and general training for predoctoral professional psychology programs, we maintain that the infusion of aging into doctoral psychology training curricula has been inadequate. In this manuscript we provide an overview of geropsychology training models and discuss the challenges involved in incorporating aging to the curriculum of pre-doctoral training in clinical psychology. Potential solutions and examples for accelerating infusion of aging knowledge base are discussed in the context of different geropsychology training models. We conclude that providing services to this rapidly growing segment of our population presents both an employment opportunity to broaden the reach of our profession as well as an ethical responsibility to train future professionals who will practice within their area of knowledge and expertise.

Medical and psychology students' knowledge and attitudes regarding aging and sexuality.

The current study surveys medical and doctoral psychology students (N = 100) from an urban northeastern university regarding knowledge and attitudes toward elderly sexuality and aging using the Facts on Aging Quiz, the Aging Sexuality Knowledge and Attitudes Scale, and measures of interest in gerontology, academic/clinical exposure to aging and sexuality, and contact with elders. The current study found that psychology students demonstrated greater aging knowledge than medical students; however, both groups showed gaps in knowledge about sexuality. Married students had greater academic/clinical exposure and greater knowledge about aging but less permissive attitudes toward elderly sexuality. Generally, knowledge about aging was the strongest correlate of knowledge about sexuality. Level of knowledge about sexuality was not associated with attitudes. Attitudes toward sexuality and aging may be more strongly tied to demographic variables reflective of religious beliefs or adherence to sociocultural norms.

Carcinomatous meningitis secondary to transitional cell bladder cancer.

We report a patient with carcinomatous meningitis secondary to known transitional cell carcinoma of the bladder. The patient presented with multiple focal neurological signs and symptoms. Diagnosis was suggested by magnetic resonance imaging and confirmed by analysis of the cerebrospinal fluid. He received whole brain radiotherapy despite a poor prognosis. To our knowledge, this is only the fifth reported case of neoplastic meningitis due to bladder cancer with confirmatory imaging and cytology and only the fourth reported case that presented with cranial nerve involvement.

Transcriptome analysis of a tau overexpression model in rats implicates an early pro-inflammatory response.

Neurofibrillary tangles comprised of the microtubule-associated protein tau are pathological features of Alzheimer's disease and several other neurodegenerative diseases, such as progressive supranuclear palsy. We previously overexpressed tau in the substantia nigra of rats and mimicked some of the neurodegenerative sequelae that occur in humans such as tangle formation, loss of dopamine neurons, and microgliosis. To study molecular changes involved in the tau-induced disease state, we used DNA microarrays at an early stage of the disease process. A range of adeno-associated virus (AAV9) vector doses for tau were injected in groups of rats with a survival interval of 2 weeks. Specific decreases in messages for dopamine-related genes validated the technique with respect to the dopaminergic cell loss observed. Of the mRNAs upregulated, there was a dose-dependent effect on multiple genes involved in immune response such as chemokines, interferon-inducible genes and leukocyte markers, only in the tau vector groups and not in dose-matched controls of either transgene-less empty vector or control green fluorescent protein vector. Histological staining for dopamine neurons and microglia matched the loss of dopaminergic markers and upregulation of immune response mRNAs in the microarray data, respectively. RT-PCR for selected markers confirmed the microarray results, with similar changes found by either technique. The mRNA data correlate well with previous findings, and underscore microgliosis and immune response in the degenerative process following tau overexpression.

Novel suppressors of alpha-synuclein toxicity identified using yeast.

The mechanism by which the Parkinson's disease-related protein alpha-synuclein (alpha-syn) causes neurodegeneration has not been elucidated. To determine the genes that protect cells from alpha-syn, we used a genetic screen to identify suppressors of the super sensitivity of the yeast Saccharomyces cerevisiae expressing alpha-syn to killing by hydrogen peroxide. Forty genes in ubiquitin-dependent protein catabolism, protein biosynthesis, vesicle trafficking and the response to stress were identified. Five of the forty genes--ENT3, IDP3, JEM1, ARG2 and HSP82--ranked highest in their ability to block alpha-syn-induced reactive oxygen species accumulation, and these five genes were characterized in more detail. The deletion of any of these five genes enhanced the toxicity of alpha-syn as judged by growth defects compared with wild-type cells expressing alpha-syn, which indicates that these genes protect cells from alpha-syn. Strikingly, four of the five genes are specific for alpha-syn in that they fail to protect cells from the toxicity of the two inherited mutants A30P or A53T. This finding suggests that alpha-syn causes toxicity to cells through a different pathway than these two inherited mutants. Lastly, overexpression of Ent3p, which is a clathrin adapter protein involved in protein transport between the Golgi and the vacuole, causes alpha-syn to redistribute from the plasma membrane into cytoplasmic vesicular structures. Our interpretation is that Ent3p mediates the transport of alpha-syn to the vacuole for proteolytic degradation. A similar clathrin adaptor protein, epsinR, exists in humans.

The relation between cognitive functioning and self-reported sleep complaints in nondemented older adults: results from the Bronx aging study.

Self-reported sleep complaints and current cognitive functioning were assessed in 375 nondemented participants ages 75 to 85 years (134 men and 241 women) as part of enrollment in the Bronx aging study, an ongoing longitudinal community-based study of cognitive aging. This study only reports on the baseline data collected from 1980 to 1983. Sleep complaints were common, occurring in about 25% of the sample. Furthermore, after controlling for depression, use of hypnotic medication, physical morbidity, age, and education, participants who reported longer sleep onset latencies performed significantly worse on measures of verbal knowledge, long-term memory and fund of information, and visuospatial reasoning. Participants who reported longer sleep durations did significantly worse on a measure of verbal short-term memory. These results suggest that perceived sleep is related to select objective cognitive abilities even when accounting for commonly recognized mediating variables, such as depression, medical comorbidity, age, or use of hypnotic medication. Given the restricted range of this nondemented sample, these results may underestimate the relation between cognitive abilities and sleep.