Dina I. Drubach

Assessing the Temporal Relationship Between Cognition and Gait: Slow Gait Predicts Cognitive Decline in the Mayo Clinic Study of Aging

BACKGROUND The association between gait speed and cognition has been reported; however, there is limited knowledge about the temporal associations between gait slowing and cognitive decline among cognitively normal individuals. METHODS The Mayo Clinic Study of Aging is a population-based study of Olmsted County, Minnesota, United States, residents aged 70-89 years. This analysis included 1,478 cognitively normal participants who were evaluated every 15 months with a nurse visit, neurologic evaluation, and neuropsychological testing. The neuropsychological battery used nine tests to compute domain-specific (memory, language, executive function, and visuospatial skills) and global cognitive z-scores. Timed gait speed (m/s) was assessed over 25 feet (7.6 meters) at a usual pace. Using mixed models, we examined baseline gait speed (continuous and in quartiles) as a predictor of cognitive decline and baseline cognition as a predictor of gait speed changes controlling for demographics and medical conditions. RESULTS Cross-sectionally, faster gait speed was associated with better performance in memory, executive function, and global cognition. Both cognitive scores and gait speed declined over time. A faster gait speed at baseline was associated with less cognitive decline across all domain-specific and global scores. These results were slightly attenuated after excluding persons with incident mild cognitive impairment or dementia. By contrast, baseline cognition was not associated with changes in gait speed. CONCLUSIONS Our study suggests that slow gait precedes cognitive decline. Gait speed may be useful as a reliable, easily attainable, and noninvasive risk factor for cognitive decline.

Enabling Task-Specific Volitional Motor Functions via Spinal Cord Neuromodulation in a Human With Paraplegia

Abstract We report a case of chronic traumatic paraplegia in which epidural electrical stimulation (EES) of the lumbosacral spinal cord enabled (1) volitional control of task‐specific muscle activity, (2) volitional control of rhythmic muscle activity to produce steplike movements while side‐lying, (3) independent standing, and (4) while in a vertical position with body weight partially supported, voluntary control of steplike movements and rhythmic muscle activity. This is the first time that the application of EES enabled all of these tasks in the same patient within the first 2 weeks (8 stimulation sessions total) of EES therapy.

Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia

Spinal sensorimotor networks that are functionally disconnected from the brain because of spinal cord injury (SCI) can be facilitated via epidural electrical stimulation (EES) to restore robust, coordinated motor activity in humans with paralysis1–3. Previously, we reported a clinical case of complete sensorimotor paralysis of the lower extremities in which EES restored the ability to stand and the ability to control step-like activity while side-lying or suspended vertically in a body-weight support system (BWS)4. Since then, dynamic task-specific training in the presence of EES, termed multimodal rehabilitation (MMR), was performed for 43 weeks and resulted in bilateral stepping on a treadmill, independent from trainer assistance or BWS. Additionally, MMR enabled independent stepping over ground while using a front-wheeled walker with trainer assistance at the hips to maintain balance. Furthermore, MMR engaged sensorimotor networks to achieve dynamic performance of standing and stepping. To our knowledge, this is the first report of independent stepping enabled by task-specific training in the presence of EES by a human with complete loss of lower extremity sensorimotor function due to SCI.In a human subject with chronic paraplegia, a combination of epidural electrical stimulation and long-term rehabilitative training have culminated in the first report of unassisted, voluntary independent stepping in a paralyzed individual.

Review of epidural spinal cord stimulation for augmenting cough after spinal cord injury

Spinal cord injury (SCI) remains a debilitating condition for which there is no cure. In addition to loss of somatic sensorimotor functions, SCI is also commonly associated with impairment of autonomic function. Importantly, cough dysfunction due to paralysis of expiratory muscles in combination with respiratory insufficiency can render affected individuals vulnerable to respiratory morbidity. Failure to clear sputum can aggravate both risk for and severity of respiratory infections, accounting for frequent hospitalizations and even mortality. Recently, epidural stimulation of the lower thoracic spinal cord has been investigated as novel means for restoring cough by evoking expiratory muscle contraction to generate large positive airway pressures and expulsive air flow. This review article discusses available preclinical and clinical evidence, current challenges and clinical potential of lower thoracic spinal cord stimulation (SCS) for restoring cough in individuals with SCI.

Electrical Neuromodulation of the Respiratory System After Spinal Cord Injury

Spinal cord injury (SCI) is a complex and devastating condition characterized by disruption of descending, ascending, and intrinsic spinal circuitry resulting in chronic neurologic deficits. In addition to limb and trunk sensorimotor deficits, SCI can impair autonomic neurocircuitry such as the motor networks that support respiration and cough. High cervical SCI can cause complete respiratory paralysis, and even lower cervical or thoracic lesions commonly result in partial respiratory impairment. Although electrophrenic respiration can restore ventilator-independent breathing in select candidates, only a small subset of affected individuals can benefit from this technology at this moment. Over the past decades, spinal cord stimulation has shown promise for augmentation and recovery of neurologic function including motor control, cough, and breathing. The present review discusses the challenges and potentials of spinal cord stimulation for restoring respiratory function by overcoming some of the limitations of conventional respiratory functional electrical stimulation systems.

Limb immobilization and corticobasal syndrome

BACKGROUND Recently, we evaluated two patients with corticobasal syndrome (CBS) who reported symptom onset after limb immobilization. Our objective was to investigate the association between trauma, immobilization and CBS. METHODS The charts of forty-four consecutive CBS patients seen in the Mayo Clinic Alzheimer Disease Research Center were reviewed with attention to trauma and limb immobilization. RESULTS 10 CBS patients (23%) had immobilization or trauma on the most affected limb preceding the onset or acceleration of symptoms. The median age at onset was 61. Six patients manifested their first symptoms after immobilization from surgery or fracture with one after leg trauma. Four patients had pre-existing symptoms of limb dysfunction but significantly worsened after immobilization or surgery. CONCLUSIONS 23 percent of patients had immobilization or trauma of the affected limb. This might have implications for management of CBS, for avoiding injury, limiting immobilization and increasing movement in the affected limb.

Publisher Correction: Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia

In the version of this article originally published, Dimitry G. Sayenko’s affiliations were not correct. The following affiliation for this author was missing: Department of Neurosurgery, Center for Neuroregeneration, Houston Methodist Research Institute, Houston, TX, USA. This affiliation has been added for the author, and the rest of the affiliations have been renumbered accordingly. The error has been corrected in the HTML and PDF versions of this article.

SEMANTIC VERSUS PHONEMIC FLUENCY IN PATIENTS WITH POSTERIOR CORTICAL ATROPHY

Background: It was shown in our previous research that individuals with PCA have challenges with internal visual imagery. (AAIC 2015 & 2016) It has also been demonstrated that mental imagery facilitates the ability to categorize objects (Wu, Duan, Tian, Wang, & Zhang, 2012). Because categorization requires mental imagery, and individuals with PCA have decreased visual imagery, we propose that individuals with PCAwill show decreased scores on a category based semantic fluency test as compared to their scores on a verbal fluency test which does not require this inner visualization. We also propose that individuals with Alzheimer’s disease will not show this discrepancy between semantic and verbal fluency scores as their internal visual imagery is not targeted by their disease allowing them to carry out semantic and verbal fluency tasks equally. Methods: Researchers will access the records of individuals who have been diagnosed with PCA and those with Alzheimer’s disease from IRB 15-000502 and compare their verbal fluency score to their semantic fluency scores. The differences in the fluency scores will then be compared to see if those with PCA show a greater decrease in their semantic fluency scores than their verbal fluency scores when compared to those with Alzheimer’s disease. Results: A pilot study was completed with 10 participants with PCA, their average semantic fluency scaled score for was 5.9, average verbal fluency scaled score 9.5. A scaled score of 9.5 places the verbal fluency scores within the average range and a scaled score of 5.9 places the semantic fluency scores in the borderline range. This discrepancy in scores shows promise in supporting our hypothesis. This data reflects only our pilot study of 10 participants, the bulk of our data is in the process of being analyzed and final semantic and verbal fluency results will be released at the conference. Conclusions:Differences in performance on semantic fluency versus verbal fluency tasks in patients with PCA may be a further indication that intrinsic visualization may be impaired. This could have some impact on a patient’s functional status and may be important in planning rehabilitation strategies in this population.

Posterior cortical atrophy (PCA) and mental imagery: A pilot study

Background:Posterior cortical atrophy (PCA) is a syndrome characterized by progressive visual perceptual difficulties often associated with other neurological manifestations including apraxia, aphasia and cognitive symptoms. Because the underlying neuropathology is frequently that of Alzheimer’s Disease, it has become known as the “visual presentation” of this disorder. While patients with PCA have difficulties with extrinsic perception, we do not know whether “intrinsic perception”, including the ability to visualize imagery, is affected. This is an important question taking into account the cognitive value of visual imagery which forms the basis of imagination, which enables a number of cognitive tasks including behavior rehearsal, anxiety reduction, recreation, motor skill enhancement and others. Since visual imagery is a subjective experiential phenomenon, it is difficult to quantify or characterize in a person. The Vividness of Visual Imagery Questionnaire (VVIQ: Marks 1973) is a valid psychometric instrument used for measuring visual imagery differences in individuals (see Richardson, 1994; McKelvie, 1995 for reviews). The questionnaire consists of sixteen items that are each completed twice; once to determine the vividness of several images recalled by the participant when their eyes are open, and then once again for the same images obtained when their eyes are closed. The test uses a self-reported 5 point Likert scale to objectively measure the vividness of each mental image. Methods: The VVIQ was administered to 7 patients with PCA and 8 age matched controls. Results: Although the vividness of mental imagery values for an image obtained with participant’s eyes open did not differ significantly from the values obtained from the typical control group [F(13,14)1⁄42.1257, p1⁄4 0.1686] it was shown that when the individuals with PCA ranked the vividness of amental image obtained with their eyes closed the vividness ranking was statistically lower than those obtained by the control participants [F(13, 14)1⁄4 4.7045, p1⁄40.0492]. Conclusions:The results of this pilot study indicate that participants with PCA maintain their ability to vividly visualize images with eyes open, however they may demonstrate a decrease in their ability to vividly visualize images with eyes closed when compared to their typical peers.

Slow gait predicts cognitive decline: A population-based cohort study

ing was an early marker of decline, with abnormalities even at the pre-MCI stage. Lower volumes of the hippocampus and the basal forebrain area were associated with an increased likelihood of MCI. Different MCI subtypes showed distinct grey matter atrophy patterns. A suite of novel plasma proteins was a good biomarker. Genome-wide association studies of cognitive performance and decline, white matter lesions and hippocampal volume have shown suggestive results which warrant replication. Conclusions: MCI is a heterogeneous condition, and its risk and protective factor studies should take age, sex and subtype into consideration. Many biomarkers, with modest predictive value, are being developed, using neuroimaging and proteomics, and novel gene discovery and replication studies are being undertaken.