Morphological changes of large layer V pyramidal neurons in cortical motor-related areas after spinal cord injury in macaque monkeys.

In primates, neurons giving rise to the corticospinal tract (CST) are distributed in several motor-related areas of the frontal lobe, such as the primary motor cortex (M1), the supplementary motor area (SMA), and the dorsal and ventral divisions of the premotor cortex (PMd, PMv). Recently, we have shown in macaque monkeys that the morphology of basal dendrites of CST neurons, i.e., large layer V pyramidal neurons, varies among the digit regions of the motor-related areas. Here, we investigated the alterations in basal dendrite morphology of CST neurons after spinal cord injury (SCI). In our monkey model, both the complexity and the spine density of basal dendrites were highly decreased throughout the areas. Notably, these events were less prominent for the PMd than for the M1, SMA, and PMv. In analyzing the density changes post-SCI of the filopodia-, thin-, stubby-, and mushroom-type spines, it was found that the density of filopodia-type spines was increased for all areas, whereas the other types of spines exhibited density decreases. Such spine density reductions were so limited for the PMd as compared to the other areas. The observed plastic changes of CST neurons may contribute to the recovery from impaired motor functions caused by SCI.

Effect of pulmonary training for community-dwelling frail older adults with chronic stroke: A randomized controlled pilot trial.

Background: Decreased pulmonary function and poor deglutition are a major risk factor for poststroke aspiration pneumonia. We analyzed the benefits of pulmonary training on pulmonary function, deglutition, and quality of life (QOL) in community-dwelling, frail elderly people with chronic stroke. Method: This study was designed as an open, randomized, controlled pilot trial. The participants, who were frail older adults with a history of stroke, were randomized to 2 rehabilitation groups: intervention group (n = 15) and control (n = 15). All participants (65-94 years) attended twelve 20-min sessions twice a week for 6 weeks of either standard rehabilitation (control group) or standard rehabilitation with pulmonary training including home pulmonary exercise (intervention group). The main outcome measures were pulmonary function (%MIP), deglutition (DRACE), and QOL (SF8ï½¥PCS), while secondary outcomes were muscle strength (grip and abdominal), thorax flexibility, 6-min walk distance, and activities in daily living. All outcomes were measured both prior to training and after the 12 sessions. Results: The intervention group showed significant improvement in %MIP (95% CI, 2.9-31.6; p < 0.01), DRACE (95% CI, -4.1-0.1; p < 0.01), and SF8ï½¥PCS (95% CI, 2.5-7.2; p < 0.01) compared with controls. There were no cognitive function decline and higher brain dysfunction. Conclusions: These results suggest that the addition of pulmonary training including home pulmonary exercise to a standard rehabilitation program could improve pulmonary function, deglutition, and QOL in frail elderly people with chronic stroke.

Swallowing Dynamics and Breathing-Swallowing Coordination Are Altered in Patients with Mild Cognitive Impairment.

INTRODUCTION: Postinspiratory activity, which is essential for laryngeal closure during swallowing to prevent aspiration of food into the airways, is reduced in a mouse model of tauopathy. Therefore, we hypothesized that patients at the stage of mild cognitive impairment (MCI) exhibit alterations in swallowing dynamics and coordination between swallowing and breathing. METHODS: We examined breathing-swallowing coordination in patients with MCI. Patients who scored ≥24 on the Mini-Mental State Examination and <26 on the Japanese version of the Montreal Cognitive Assessment were recruited at Sumoto Itsuki Hospital. Parameters associated with breathing-swallowing coordination were assessed using a combination of two sensors: a respiratory flow sensor and a piezoelectric sensor attached to the skin surface of the anterior neck. RESULTS: Nineteen patients met the criteria for MCI; 16 of these patients (79.5 ± 9.1 years old) scored <3 on the 10-item Eating Assessment Tool and were enrolled in the study. Their data were compared with those of an age-matched elderly cohort (79.9 ± 2.9 years old). The frequencies of swallowing during inspiration and swallowing immediately followed by inspiration in patients with MCI were 6.9% and 9.6%, respectively; these frequencies were not significantly different from those of the age-matched elderly cohort. However, the timing of swallowing in the respiratory cycle was significantly delayed in the MCI patients, and both time from the onset to the peak of laryngeal elevation and the duration between the onset of rapid laryngeal elevation and the time when the larynx returned to the resting position were significantly lengthened in this group. CONCLUSION: At the stage of MCI, breathing-swallowing coordination has already started to decline.

An enhanced therapeutic effect of repetitive transcranial magnetic stimulation combined with antibody treatment in a primate model of spinal cord injury.

Repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (MI) is expected to provide a therapeutic impact on spinal cord injury (SCI). On the other hand, treatment with antibody against repulsive guidance molecule-a (RGMa) has been shown to ameliorate motor deficits after SCI in rodents and primates. Facilitating activity of the corticospinal tract (CST) by rTMS following rewiring of CST fibers by anti-RGMa antibody treatment may exert an enhanced effect on motor recovery in a primate model of SCI. To address this issue, we examined whether such a combined therapeutic strategy could contribute to accelerating functional restoration from SCI. In our SCI model, unilateral lesions were made between the C6 and the C7 level. Two macaque monkeys were used for each of the combined therapy and antibody treatment alone, while one monkey was for rTMS alone. The antibody treatment was continuously carried out for four weeks immediately after SCI, and rTMS trials applying a thermoplastic mask and a laser distance meter lasted ten weeks. Behavioral assessment was performed over 14 weeks after SCI to investigate the extent to which motor functions were restored with the antibody treatment and/or rTMS. While rTMS without the preceding antibody treatment produced no discernible sign for functional recovery, a combination of the antibody and rTMS exhibited a greater effect, especially at an early stage of rTMS trials, on restoration of dexterous hand movements. The present results indicate that rTMS combined with anti-RGMa antibody treatment may exert a synergistic effect on motor recovery from SCI.

Morphological features of large layer V pyramidal neurons in cortical motor-related areas of macaque monkeys: analysis of basal dendrites.

In primates, large layer V pyramidal neurons located in the frontal motor-related areas send a variety of motor commands to the spinal cord, giving rise to the corticospinal tract, for execution of skilled motor behavior. However, little is known about the morphological diversity of such pyramidal neurons among the areas. Here we show that the structure of basal dendrites of the large layer V pyramidal neurons in the dorsal premotor cortex (PMd) is different from those in the other areas, including the primary motor cortex, the supplementary motor area, and the ventral premotor cortex. In the PMd, not only the complexity (arborization) of basal dendrites, i.e., total dendritic length and branching number, was poorly developed, but also the density of dendritic spines was so low, as compared to the other motor-related areas. Regarding the distribution of the three dendritic spine types identified, we found that thin-type (more immature) spines were prominent in the PMd in comparison with stubby- and mushroom-type (more mature) spines, while both thin- and stubby-type spines were in the other areas. The differential morphological features of basal dendrites might reflect distinct patterns of motor information processing within the large layer V pyramidal neurons in individual motor-related areas.

Factors related to physical and mental components of quality of life in the community-dwelling frail older persons.

[Purpose] The aim of this study was to investigate factors associated with changes in both the physical and mental components of quality of life (QOL) in of community-dwelling frail older persons in long-term care and to clarify which aspects are important to maintaining physical and mental components of QOL. [Participants and Methods] In this 1 year follow-up cohort study, participants were older persons from a single day care rehabilitation center in Japan. The Medical Outcome Study 8-Item Short-Form Health Survey (MOS-SF8), which gives both physical component summary (PCS) and mental component summary (MCS) scores, was used as the main QOL assessment. Participants were divided according to their level of QOL maintenance according to changes in PCS and MCS scores over the study period, and the variables were compared between the groups. [Results] PCS domain was significantly associated with forced vital capacity and the MCS domain was significantly associated with the Geriatric Depression Scale and Dysphagia Risk Assessment for the Community-Dwelling Elderly Test. [Conclusion] Depression, reduced pulmonary function, and reduced deglutition ability were independently related to low QOL. Assessment of these factors could be beneficial for maintaining the physical and mental components of QOL in community-dwelling frail older persons in long-term care.

Effect of respiratory rehabilitation for frail older patients with musculoskeletal disorders: a randomized controlled trial.

OBJECTIVE: To investigate the effects of respiratory rehabilitation on respiratory function, swallowing in community-dwelling frail older patients with musculoskeletal disorders. DESIGN: Randomized open-label controlled trial. SETTING: Day-care facility in a rehabilitation hospital in Japan. SUBJECTS: A total of 63 participants with musculoskeletal disorders (intervention group: n = 31; control group: n = 32) completed the randomized controlled trial. INTERVENTIONS: All participants received 12 20-min sessions twice a week for 6 weeks of either typical rehabilitation (control) or typical rehabilitation with respiratory rehabilitation (intervention). MAIN MEASURES: Outcome measures were assessed prior to rehabilitation and after 12 sessions. The measures included: respiratory function, swallowing function, exercise tolerance, 6-min walk distance, thorax flexibility, muscle strength (grip and abdominal), activities of daily living, and quality of life. RESULTS: Participants in the intervention group showed significantly greater improvement in respiratory function (95% confidence interval (CI), 3.8-6.6; p = 0.01), swallowing function (95% CI -1.8-0.6; p = 0.01), and quality of life (SF8 Physical Summary Score) (95% CI 2.4-7.1; p = 0.01) compared with those in the control group. CONCLUSION: Addition of respiratory rehabilitation to a typical rehabilitation programme could improve not only respiratory and swallowing function, but also quality of life, in frail older patients.

Cilostazol add-on therapy in patients with mild dementia receiving donepezil: a retrospective study.

GOAL: Combinatorial therapy directed at both vascular and neurodegenerative aspects of dementia may offer a promising strategy for treatment of dementia, which often has a multifactorial basis in the elderly. We investigated whether the phosphodiesterase III inhibitor cilostazol, which is often used in the prevention of stroke and peripheral artery disease, may delay cognitive decline in the elderly receiving donepezil. METHODS: Medical records were retrospectively surveyed to identify patients who had received donepezil for more than one year and had undergone Mini-Mental State Examination (MMSE) at least at two time points. Those with an initial MMSE score of less than 27 points were subjected to analysis (n = 156), with a cut-point of 21/22 applied to assign them to mild (n = 70) and moderate/severe (n = 86) dementia. The change of total MMSE score per year was compared between patients who had received donepezil and those given both donepezil and cilostazol. FINDINGS: In patients with mild dementia who had received donepezil and cilostazol (n = 34; 77.2±6.8 years old), the annual change in MMSE score was -0.5±1.6 during an observational period of 28.6±11.7 months, with those receiving donepezil only (n = 36; 78.4±6.5 years old) scoring less (-2.2±4.1) during 30.4±12.8 months with a statistical intergroup difference (p = 0.022). Multivariate analysis showed that absence of cilostazol treatment was the only significant predictor of MMSE decline. A positive effect of cilostazol was found in three subscale scores of MMSE, orientation for time or place and delayed recall. By clear contrast, in patients with moderate/severe dementia, there were no intergroup differences in decrease of total or subscale MMSE scores between the two groups. CONCLUSIONS: These results suggest potential for cilostazol treatment in the suppression of cognitive decline in patients receiving donepezil with mild dementia but not in those with moderate/severe dementia.

Cilostazol improves cognitive function in patients with mild cognitive impairment: a retrospective analysis.

BACKGROUND AND PURPOSE: Cerebral ischemia and accumulation of amyloid ß (Aß) are major risk factors for the development of dementia, including vascular dementia and Alzheimer's disease. Cilostazol, an antiplatelet drug, has been shown to improve cerebral circulation and reduce accumulation of Aß. In this study, the long-term effect of cilostazol on cognitive function was investigated retrospectively. METHODS: Medical records at Sumotoitsuki Hospital were surveyed to find all patients treated with cilostazol and evaluated by the Mini-Mental State Examination (MMSE) during at least two visits separated by an interval of more than 6 months. Patients receiving anti-dementia drugs were excluded. Temporal changes in MMSE scores were compared between patients treated with cilostazol (n = 70) and those who ceased administration of this drug (n = 22). The mean follow-up period was 691 days. RESULTS: Decrease in MMSE score was significantly ameliorated by administration of cilostazol. Subgroup analysis revealed that cilostazol significantly improved MMSE score in patients with mild cognitive impairment, though no significant effect was observed in patients with normal cognitive function or dementia. CONCLUSIONS: Although there are limitations to such a retrospective study, these results significantly encourage undertaking a prospective cohort study to determine the effect of cilostazol on mild cognitive impairment where no treatments currently exist.