Effects of Beta-Amyloid on Resting State Functional Connectivity Within and Between Networks Reflect Known Patterns of Regional Vulnerability.

Beta-amyloid (Aß) deposition is one of the hallmarks of Alzheimer's disease (AD). However, it is also present in some cognitively normal elderly adults and may represent a preclinical disease state. While AD patients exhibit disrupted functional connectivity (FC) both within and between resting-state networks, studies of preclinical cases have focused primarily on the default mode network (DMN). The extent to which Aß-related effects occur outside of the DMN and between networks remains unclear. In the present study, we examine how within- and between-network FC are related to both global and regional Aß deposition as measured by [(11)C]PIB-PET in 92 cognitively normal older people. We found that within-network FC changes occurred in multiple networks, including the DMN. Changes of between-network FC were also apparent, suggesting that regions maintaining connections to multiple networks may be particularly susceptible to Aß-induced alterations. Cortical regions showing altered FC clustered in parietal and temporal cortex, areas known to be susceptible to AD pathology. These results likely represent a mix of local network disruption, compensatory reorganization, and impaired control network function. They indicate the presence of Aß-related dysfunction of neural systems in cognitively normal people well before these areas become hypometabolic with the onset of cognitive decline.

Upslope treadmill exercise enhances motor axon regeneration but not functional recovery following peripheral nerve injury.

Following peripheral nerve injury, moderate daily exercise conducted on a level treadmill results in enhanced axon regeneration and modest improvements in functional recovery. If the exercise is conducted on an upwardly inclined treadmill, even more motor axons regenerate successfully and reinnervate muscle targets. Whether this increased motor axon regeneration also results in greater improvement in functional recovery from sciatic nerve injury was studied. Axon regeneration and muscle reinnervation were studied in Lewis rats over an 11 wk postinjury period using stimulus evoked electromyographic (EMG) responses in the soleus muscle of awake animals. Motor axon regeneration and muscle reinnervation were enhanced in slope-trained rats. Direct muscle (M) responses reappeared faster in slope-trained animals than in other groups and ultimately were larger than untreated animals. The amplitude of monosynaptic H reflexes recorded from slope-trained rats remained significantly smaller than all other groups of animals for the duration of the study. The restoration of the amplitude and pattern of locomotor EMG activity in soleus and tibialis anterior and of hindblimb kinematics was studied during treadmill walking on different slopes. Slope-trained rats did not recover the ability to modulate the intensity of locomotor EMG activity with slope. Patterned EMG activity in flexor and extensor muscles was not noted in slope-trained rats. Neither hindblimb length nor limb orientation during level, upslope, or downslope walking was restored in slope-trained rats. Slope training enhanced motor axon regeneration but did not improve functional recovery following sciatic nerve transection and repair.

Relationships Between Cognitive Screening Composite Scores and Pain Intensity and Pain Disability in Adults With/At Risk for Knee Osteoarthritis.

OBJECTIVES: Chronic pain, cognitive deficits, and pain-related disability are interrelated. The prevalence of chronic pain and undiagnosed cognitive difficulties in middle age and older adults is increasing. Of the cognitive systems, executive function and episodic memory are most relevant to chronic pain. We examined the hypothesis that cognitive screening composite scores for executive function and memory would negatively associate with pain intensity and pain disability in a group of middle-aged and older adults with knee pain with or at risk for osteoarthritis. METHODS: A total of 120 adults (44 men/76 women), an average age of 59 years, participated in the study. Demographic, health history, clinical pain, and cognitive measures were completed. Relationships between pain intensity, pain disability, and the Montreal Cognitive Assessment (MoCA) total and composite scores were examined with relevant covariates in the model. RESULTS: MoCA raw scores ranged from 13 to 30 with a mean score of 23.9. Pain intensity was negatively associated with overall MoCA total and executive function and memory composite scores. Pain disability over the previous 6 months was negatively associated with executive function, while pain disability over the past 48 hours was not associated with executive function. CONCLUSION: The results of the current study demonstrates associations between pain metrics and cognitive domain scores within a common cognitive screening tool.

Mild Cognitive Impairment and Decline in Resting State Functional Connectivity after Total Knee Arthroplasty with General Anesthesia.

BACKGROUND: Research shows that older adults can have a decline in three key resting state networks (default mode network, central executive network, and salience network) after total knee arthroplasty and that patients' pre-surgery brain and cognitive integrity predicts decline. OBJECTIVES: First, to assess resting state network connectivity decline from the perspective of nodal connectivity changes in a larger older adult surgery sample. Second, to compare pre-post functional connectivity changes in mild cognitive impairment (MCI) versus non-MCI. METHODS: Surgery (n = 69) and non-surgery (n = 65) peers completed a comprehensive preoperative neuropsychological evaluation and pre- and acute (within 48 hours) post-surgery/pseudo-surgery functional brain magnetic resonance imaging scan. MCI was classified within both (MCI surgery, n = 13; MCI non-surgery, n = 10). Using standard coordinates, we defined default mode network, salience network, central executive network, and the visual network (serving as a control network). The functional connectivity of these networks and brain areas (nodes) that make up these networks were examined for pre-post-surgery changes through paired samples t-test and ANOVA. RESULTS: There was a decline in RSN connectivity after surgery (p < 0.05) only in the three cognitive networks (not the visual network). The default mode and salience network showed nodal connectivity changes (p < 0.01). MCI surgery had greater functional connectivity decline in DMN and SN. Non-surgery participants showed no significant functional connectivity change. CONCLUSION: Surgery with general anesthesia selectively alters functional connectivity in major cognitive resting state networks particularly in DMN and SN. Participants with MCI appear more vulnerable to these functional changes.

Neural compensation in older people with brain amyloid-ß deposition.

Recruitment of extra neural resources may allow people to maintain normal cognition despite amyloid-ß (Aß) plaques. Previous fMRI studies have reported such hyperactivation, but it is unclear whether increases represent compensation or aberrant overexcitation. We found that older adults with Aß deposition had reduced deactivations in task-negative regions, but increased activation in task-positive regions related to more detailed memory encoding. The association between higher activity and more detailed memories suggests that Aß-related hyperactivation is compensatory.