Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise.

Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.±6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (Pcorrected <0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.

The relationship between knee adduction moment and cartilage and meniscus morphology in women with osteoarthritis.

OBJECTIVE: The aim of this cross-sectional study is to investigate the relationship between knee adduction moment and knee adduction angular impulse and meniscus, cartilage and bone morphology in women with knee osteoarthritis (OA). METHOD: Forty-five women aged >40 years with OA in at least one knee, according to American College of Rheumatology clinical criteria were studied. The knee joint loading was assessed by three-dimensional motion analysis system during gait. Three Tesla magnetic resonance imaging (MRI) with a coronal T2-weighted spin echo sequence was used for evaluating meniscus pathology, and a coronal T1-weighted gradient echo sequence for quantifying cartilage morphology and bone surface size. Cartilage thickness, denuded area and subchondral area in the femorotibial joint was measured using custom software. RESULTS: A higher peak knee adduction moment was observed in participants with medial compared to those with lateral tears (2.92+/-1.06 vs -0.46+/-1.7, P<0.001). Participants with a higher knee adduction moment displayed a larger medial meniscus extrusion (r=0.532, P<0.001) and a lower medial meniscus height (r=-0.395, P=0.010). The inverse relationship was observed for the lateral meniscus. A higher knee adduction moment was also associated with a higher ratio of the medial to lateral tibial subchondral bone area (r=0.270, P=0.035). By contrast, cartilage thickness and denuded areas in the femur and tibia were not related to the knee adduction moment. Similar results were found for the relationship between knee adduction angular impulse and meniscus, cartilage and bone morphology. CONCLUSIONS: Dynamic knee joint loading is significantly related to meniscus pathology and bone size, but not to cartilage thickness in women with OA.

Midlife managerial experience is linked to late life hippocampal morphology and function.

An active cognitive lifestyle has been suggested to have a protective role in the long-term maintenance of cognition. Amongst healthy older adults, more managerial or supervisory experiences in midlife are linked to a slower hippocampal atrophy rate in late life. Yet whether similar links exist in individuals with Mild Cognitive Impairment (MCI) is not known, nor whether these differences have any functional implications. 68 volunteers from the Sydney SMART Trial, diagnosed with non-amnestic MCI, were divided into high and low managerial experience (HME/LME) during their working life. All participants underwent neuropsychological testing, structural and resting-state functional MRI. Group comparisons were performed on hippocampal volume, morphology, hippocampal seed-based functional connectivity, memory and executive function and self-ratings of memory proficiency. HME was linked to better memory function (p = 0.024), mediated by larger hippocampal volume (p = 0.025). More specifically, deformation analysis found HME had relatively more volume in the CA1 sub-region of the hippocampus (p < 0.05). Paradoxically, this group rated their memory proficiency worse (p = 0.004), a result correlated with diminished functional connectivity between the right hippocampus and right prefrontal cortex (p < 0.001). Finally, hierarchical regression modelling substantiated this double dissociation.

Normative volume difference between the dominant and nondominant upper limbs in healthy older women.

BACKGROUND: Upper limb lymphedema is a possible consequence of the treatment for breast cancer. Accurate detection of swelling is important in implementing appropriate treatment. Currently used diagnostic cut-offs for excess volume have been chosen for ease of use and are not based on normative differences. The aim of this study, therefore, was to determine the normal inter-limb variance for healthy older women and identify statistically-based diagnostic cut-offs for both circumference and volume. METHODS AND RESULTS: Two hundred and four healthy women, over the age of 40 years, with no history of treatment for breast cancer or lymphedema, underwent measurement of their upper limbs with a perometer. Using the associated software, the circumference of the limb was determined at a number of set points along the limb and the volume of the intervening segments recorded. Segment volumes were also calculated from the circumferential measurements using the formulae for a truncated cone and cylinder. The mean inter-limb difference found was small but a large range was seen for all of the circumference and volume measurements. Dominance was found to have a significant effect on the limb size. Regression analysis showed that an individual's age was negatively related to their inter-limb difference. Diagnostic cut-offs, set at three standard deviations above the mean, were determined. CONCLUSIONS: New circumference and volume criteria based on normative data, taking arm dominance into consideration, will allow for more accurate diagnosis of changes in limb volume, allowing treatment to be started and monitored appropriately.

Degenerative meniscus tears and mobility impairment in women with knee osteoarthritis.

OBJECTIVE: Meniscus tears are often presumed to be associated with a traumatic event, but they can also occur as a result of the cartilage degeneration process in osteoarthritis (OA). The aim of this paper is to describe the prevalence and clinical correlates of degenerative meniscus tears in women with knee OA. METHOD: The subjects were women screened for a double-blind, sham-exercise controlled clinical trial for women over 40 years of age with OA in at least one knee, according to American College of Rheumatology (ACR) clinical criteria. The presence of meniscus tears was assessed via a 3T Intera (Philips Medical Systems) magnetic resonance image (MRI). Clinical examination included a history of arthritis onset and physical examination of the lower extremities. Physical assessments included body composition, muscle strength, walking endurance, gait velocity, and balance. In addition, pain and disability secondary to OA, physical self-efficacy, depressive symptoms, habitual physical activity level and quality of life were assessed via questionnaires. RESULTS: Almost three-quarters (73%) of the 41 subjects had a medial, lateral, or bilateral meniscus tear by MRI. Walking endurance and balance performance were significantly impaired in subjects with a degenerative meniscus tear, compared to subjects without tears, despite similar OA duration, symptoms, and disability, body composition, and other clinical characteristics. CONCLUSION: Meniscus tears, diagnosed by MRI, are very common in older women with knee OA, particularly in the medial compartment. These incidentally discovered tears are associated with clinically relevant impairments of balance and walking endurance relative to subjects without meniscus tears. The explanation for this association requires further study.

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The effects of lateral wedge insole with and without sub-talar strap on pain, arthritic symptoms, functional performance, sports and recreational activities, and knee related quality of life in patients with medial compartment knee osteoarthritis were compared. Community-dwelling men and women aged over 40 years with medial compartment knee osteoarthritis, grades I or II based on Kellgrene and Lawrence grading system were participated in this study. They were randomly allocated in two different groups; lateral wedge insole with and without sub-talar strap. Both groups were required to wear the insoles at home for the duration of four weeks, approximately 5 to 10 hours per day. Participants were asked to complete the Farsi version of Knee injury and Osteoarthritis Outcome Score [KOOS] questionnaire at baseline and at follow-up. The reliability of KOOS for measuring short term and long term symptoms and function in Iranian patients with knee injuries and osteoarthritis has been reported previously. The changes in KOOS subscales were significantly different in both groups over time. Contrary to our hypothesis, the interaction effect was significant between the two groups following our intervention in terms of symptoms, daily living functions, sports and recreational activities, and knee related quality of life, unless pain score. The result of this study suggests that both of the insoles improved pain, symptoms, function in daily living, sports and recreation activities and knee related quality of life in patients with mild medial compartment knee osteoarthritis. However, use of sub-talar strap with lateral wedge insole would be the better prescription for insoles in these patients.