Amelia J. Anderson-Mooney

Cognition and Depression Following Deep Brain Stimulation of the Subthalamic Nucleus and Globus Pallidus Pars Internus in Parkinson’s Disease: A Meta-Analysis

Parkinson’s disease (PD) is a common, degenerative disorder of the central nervous system. Individuals experience predominantly extrapyramidal symptoms including resting tremor, rigidity, bradykinesia, gait abnormalities, cognitive impairment, depression, and neurobehavioral concerns. Cognitive impairments associated with PD are diverse, including difficulty with attention, processing speed, executive functioning, memory recall, visuospatial functions, word-retrieval, and naming. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is FDA approved and has been shown to be effective in reducing motor symptoms of PD. Studies have found that stimulating STN and GPi are equally effective at improving motor symptoms and dyskinesias; however, there has been discrepancy as to whether the cognitive, behavioral, and mood symptoms are affected differently between the two targets. The present study used random-effects meta-analytic models along with a novel p-curve analytic procedure to compare the potential cognitive and emotional impairments associated with STN-DBS in the current literature to those associated with GPi-DBS. Forty-one articles were reviewed with an aggregated sample size of 1622 patients. Following STN-DBS, small declines were found in psychomotor speed, memory, attention, executive functions, and overall cognition; and moderate declines were found in both semantic and phonemic fluency. However, GPi-DBS resulted in fewer neurocognitive declines than STN-DBS (small declines in attention and small-moderate declines in verbal fluency). With regards to its effect on depression symptomatology, both GPi-DBS and STN-DBS resulted in lower levels of depressive symptoms post-surgery. From a neurocognitive standpoint, both GPi-DBS and STN-DBS produce subtle cognitive declines but appears to be relatively well tolerated.

Development, Validation and Application of a New Fornix Template for Studies of Aging and Preclinical Alzheimer's Disease

We developed a merged younger-older adult template of the fornix and demonstrated its utility for studies of aging and preclinical Alzheimers disease (AD). In Experiment 1, probabilistic tractography was used to reconstruct the fornix in younger and older adults and successful streamlines were then averaged to create a merged template in standard space. The new template includes the majority of the fornix from the hippocampal formation to the subcallosal region and the thalamus/hypothalamus. In Experiment 2, the merged template was validated as an appropriate measure for studies of aging, with comparisons against manual tracing measures indicating identical spatial coverage in younger and older adult groups. In Experiment 3, the merged template was found to outperform age-specific templates in measures of sensitivity and specificity computed on diffusion tensor imaging data of an independent participant cohort. In Experiment 4, relevance to preclinical AD was demonstrated via associations between fractional anisotropy within the new fornix template and cerebrospinal fluid markers of AD pathology (Aβ42 and the t-tau/Aβ42 ratio) in a third independent cohort of cognitively normal older adults. Our new template provides an appropriate measure for use in future studies seeking to characterize microstructural alterations in the fornix associated with aging and preclinical AD.

Dispositional Forgiveness and Meaning- Making: The Relative Contributions of Forgiveness and Adult Attachment Style to Struggling or Enduring With God

The Diagnostic and Statistical Manual of Mental Disorders (fifth edition) continues to recognize the role of spirituality in mental health by including a V-Code (V62.89) for Religious or Spiritual Problem (American Psychiatric Association, 2013). As individuals may question basic religious assumptions following negative life events, this study examines attachment style, dispositional forgiveness, and spiritual response after negative life events. Analyses revealed that both forgiveness and secure attachment significantly predicted spiritual struggle and endurance. However, attachment style and forgiveness did not significantly combine to predict spiritual response. Results indicate that both attachment style and dispositional forgiveness are important in spiritual functioning.

Neurocognitive & neuropsychiatric phenotypes of PARK2-associated early-onset Parkinson's disease in two siblings.

Most Parkinson’s disease (PD) cases are idiopathic, but some atients have an established genetic correlate for their parkinonism, including alterations of LRRK2, PINK1, SCNA, PARK7, and ARK2 [1]. PARK2 (also known as PRKN and parkin RBR E3 ubiquiin protein ligase) is located on chromosome 6 between base pairs 61,768,589 and 163,148,833, with over 200 known mutations. ARK2 encodes transcription of parkin ubiquitin ligase, which is hought to operate in marking excess or damaged cerebral proeins for disposal. PARK2 mutations may disrupt these operations, ith clinical symptom manifestation resulting from the subseuent deposition of abnormal proteins. Mutations have also been onnected with increased dopaminergic MAO metabolism and nhibited glutaminergic transmission in murine models [2]. Autosomal recessive mutations of PARK2 are relatively comon in early-onset PD (EOPD) [1], often emerging before age 0 and sometimes before age 20 (juvenile onset). The associated linical phenotype is often characterized by marked anticholineric sensitivity; early, prominent dystonia; and treatment-induced yskinesias. The associated cognitive profile has not been well

Gait dyspraxia as a clinical marker of cognitive decline in Down syndrome: A review of theory and proposed mechanisms

Down syndrome (DS) is the most common genetic cause of intellectual disability in children. With aging, DS is associated with an increased risk for Alzheimers disease (AD). The development of AD neuropathology in individuals with DS can result in further disturbances in cognition and behavior and may significantly exacerbate caregiver burden. Early detection may allow for appropriate preparation by caregivers. Recent literature suggests that declines in gait may serve as an early marker of AD-related cognitive disorders; however, this relationship has not been examined in individuals with DS. The theory regarding gait dyspraxia and cognitive decline in the general population is reviewed, and potential applications to the population with individuals with DS are highlighted. Challenges and benefits in the line of inquiry are discussed. In particular, it appears that gait declines in aging individuals with DS may be associated with known declines in frontoparietal gray matter, development of AD-related pathology, and white matter losses in tracts critical to motor control. These changes are also potentially related to the cognitive and functional changes often observed during the same chronological period as gait declines in adults with DS. Gait declines may be an early marker of cognitive change, related to the development of underlying AD-related pathology, in individuals with DS. Future investigations in this area may provide insight into the clinical changes associated with development of AD pathology in both the population with DS and the general population, enhancing efforts for optimal patient and caregiver support and propelling investigations regarding safety/quality of life interventions and disease-modifying interventions.

The Nervous System and Addictions: Essentials for Clinicians

Understanding neurobiology forms a strong foundation for investigating addictive behavior. Brain structure is briefly discussed, including major cortical and subcortical structures, white matter pathways, other vital systems, and cellular components. The mesocorticolimbic system and dopamine are discussed in light of psychoactive substances. Mesocorticolimbic changes have been documented in the transition from recreational substance use to chronic dependence, reflecting a change from the basic positive reinforcement of initial use to the development of a negative reinforcement paradigm due to the avoidance of negative withdrawal consequences. Anticipation and craving reflect persistent changes in the mesolimbic system attributable to substance dependence. Not only do mesolimbic systemic operations alter in the presence of substances, but responses to substances within the structures themselves also appear to change. These principles are applied to the practical understanding of pathological compulsive behaviors, including gambling and hoarding, and the chapter then closes with a brief discussion of the societal value of insight into the neurological effects of substances.Abstract Understanding neurobiology forms a strong foundation for investigating addictive behavior. Brain structure is briefly discussed, including major cortical and subcortical structures, white matter pathways, other vital systems, and cellular components. The mesocorticolimbic system and dopamine are discussed in light of psychoactive substances. Mesocorticolimbic changes have been documented in the transition from recreational substance use to chronic dependence, reflecting a change from the basic positive reinforcement of initial use to the development of a negative reinforcement paradigm due to the avoidance of negative withdrawal consequences. Anticipation and craving reflect persistent changes in the mesolimbic system attributable to substance dependence. Not only do mesolimbic systemic operations alter in the presence of substances, but responses to substances within the structures themselves also appear to change. These principles are applied to the practical understanding of pathological compulsive behaviors, including gambling and hoarding, and the chapter then closes with a brief discussion of the societal value of insight into the neurological effects of substances.

Peripheral nerve grafts implanted into the substantia nigra in patients with Parkinson’s disease during deep brain stimulation surgery: 1-year follow-up study of safety, feasibility, and clinical outcome

OBJECTIVECurrently, there is no treatment that slows or halts the progression of Parkinsons disease. Delivery of various neurotrophic factors to restore dopaminergic function has become a focus of study in an effort to fill this unmet need for patients with Parkinsons disease. Schwann cells provide a readily available source of such factors. This study presents a 12-month evaluation of safety and feasibility, as well as the clinical response, of implanting autologous peripheral nerve grafts into the substantia nigra of patients with Parkinsons disease at the time of deep brain stimulation (DBS) surgery.METHODSStandard DBS surgery targeting the subthalamic nucleus was performed in 8 study participants. After DBS lead implantation, a section of the sural nerve containing Schwann cells was harvested and unilaterally grafted to the substantia nigra. Adverse events were continually monitored. Baseline clinical data were obtained during standard preoperative evaluations. Clinical outcome data were obtained with postoperative clinical evaluations, neuropsychological testing, and MRI at 1 year after surgery.RESULTSAll 8 participants were implanted with DBS systems and grafts. Adverse event profiles were comparable to those of standard DBS surgery with the exception of 1 superficial infection at the sural nerve harvest site. Three participants also reported numbness in the distribution of the sural nerve distal to the harvest site. Motor scores on Unified Parkinsons Disease Rating Scale (UPDRS) part III while the participant was off therapy at 12 months improved from baseline (mean ± SD 25.1 ± 15.9 points at 12 months vs 32.5 ± 9.7 points at baseline). An analysis of the lateralized UPDRS scores also showed a greater overall reduction in scores on the side contralateral to the graft.CONCLUSIONSPeripheral nerve graft delivery to the substantia nigra at the time of DBS surgery is feasible and safe based on the results of this initial pilot study. Clinical outcome data from this phase I trial suggests that grafting may have some clinical benefit and certainly warrants further study to determine if this is an efficacious and neurorestorative therapy.Clinical trial registration no.: NCT01833364 (clinicaltrials.gov).

DETECTION OF COGNITIVE IMPAIRMENT AFTER ACUTE ISCHEMIC STROKE: VALIDATION OF BRIEF AND MORE COMPREHENSIVE COGNITIVE SCREENING INSTRUMENTS AND IMPLICATIONS FOR BEST PRACTICE

Background: Prior to cognitive decline identifiable via objective testing, older adults often become aware of subtle changes in memory and thinking that impact daily life. This preclinical period, termed subjective cognitive impairment (SCI), may be a key to early detection of dementia-related decline. However, current measurement of SCI is inconsistent across studies and does not consider the multiple ways older adults interpret and answer such questions. Methods:Cognitive interviewing, a structured approach to analyzing sources of response error when individuals respond to questions, was used to systematically appraise older adults’ interpretation of and response to twenty self-report SCI assessment items commonly used in research. The sample (n1⁄455) included independently-living adults age 60 or over with SCI and without dementia; purposive sampling was used to obtain a range of SCI severity. A cognitive interview guide utilized verbal probing techniques to evaluate comprehension, interpretation, difficulty, and potential alternate wording of each item. Interviews were audio-recorded and transcribed, then coded for problem identification using the Question Appraisal System (QAS-99). Results: The most common problem area identified across SCI items was clarity: problems related to communicating the intent or meaning of the question. Specific problems in this area included vague wording that led to multiple ways of interpreting the question (e.g., lack of specificity in identifying important vs. unimportant instances of forgetting) as well as unspecified reference periods (e.g., differences in interpretation of the time frame “happened recently”). Additionally, some questions were inherently affect-laden even when affective language was not included (e.g., comparing one’s memory to peers) and led to respondent resistance when answering. Conclusions:Identifying problems with current assessment items and individual differences in reporting biases across older adult respondents will help to inform future SCI assessment methods. These findings could also aid in the interpretation of current evidence regarding the associations among SCI and a variety of negative outcomes in older adults.

Pick’s Disease: The Evolution of Theory and Knowledge in Neurodegenerative Tauopathies

“Pick’s disease” was originally conceptualized as a single pathological entity, but histopathological investigations failed to verify that construct. Instead, a wide variety of pathologies and phenotypical expressions were implicated. Cases with prototypical Pick’s inclusions, seemingly uncommon, are now called frontotemporal lobar degeneration (FTLD)-tau with Pick bodies. Other pathologies originally subsumed by “Pick’s disease” are now considered either part of the “Pick complex” or included under the large FTLD umbrella, including several tauopathies and FTLD positive for TDP-43, ubiquitin, and fused-in sarcoma. In spite of these efforts to classify FTLD-tau with Pick bodies more accurately in the grand scheme of neurodegeneration, clinical identification remains challenging due to overlapping, varied clinical phenotypes. Barriers to accurate in vivo diagnosis result in increased risk for clinical misdiagnosis. Clinicians and researchers alike are encouraged to consider the increasingly recognized roles of cooccurring pathologies in diagnosis and treatment innovations.“Pick’s disease” was originally conceptualized as a single pathological entity, but histopathological investigations failed to verify that construct. Instead, a wide variety of pathologies and phenotypical expressions were implicated. Cases with prototypical Pick’s inclusions, seemingly uncommon, are now called frontotemporal lobar degeneration (FTLD)-tau with Pick bodies. Other pathologies originally subsumed by “Pick’s disease” are now considered either part of the “Pick complex” or included under the large FTLD umbrella, including several tauopathies and FTLD positive for TDP-43, ubiquitin, and fused-in sarcoma. In spite of these efforts to classify FTLD-tau with Pick bodies more accurately in the grand scheme of neurodegeneration, clinical identification remains challenging due to overlapping, varied clinical phenotypes. Barriers to accurate in vivo diagnosis result in increased risk for clinical misdiagnosis. Clinicians and researchers alike are encouraged to consider the increasingly recognized roles of cooccurring pathologies in diagnosis and treatment innovations.