***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Mild cognitive impairment ( MCI ) is a condition characterized by memory problems that are more severe than the normal cognitive changes due to aging , but less severe than dementia . Reduced working memory ( WM ) is regarded as one of the core symptoms of an MCI condition . Recent studies have indicated that WM can be improved through computer-based training . The objective of this study is to evaluate if WM training is effective in improving cognitive function in elderly patients with MCI , and if cognitive training induces structural changes in the white and gray matter of the brain , as assessed by structural MRI . Methods / Design sThe proposed study is a blinded , r and omized , controlled trail that will include 90 elderly patients diagnosed with MCI at a hospital-based memory clinic . The participants will be r and omized to either a training program or a placebo version of the program . The intervention is computerized WM training performed for 45 minutes of 25 sessions over 5 weeks . The placebo version is identical in duration but is non-adaptive in the difficulty level of the tasks . Neuropsychological assessment and structural MRI will be performed before and 1 month after training , and at a 5-month folllow-up . Discussion If computer-based training results in positive changes to memory functions in patients with MCI this may represent a new , cost-effective treatment for MCI . Secondly , evaluation of any training-induced structural changes to gray or white matter will improve the current underst and ing of the mechanisms behind effective cognitive interventions in patients with MCI.Trial registration Clinical Trials.gov NCT01991405 . November 18 , 2013 Background and Purpose — MRI is more sensitive than CT for detection of  age-related white matter changes ( ARWMC ) .  Most rating scales estimate the degree and distribution of ARWMC either on CT or on MRI , and they differ in many aspects . This makes it difficult to compare CT and MRI studies . To be able to study the evolution and possible effect of drug treatment on ARWMC in large patient sample s , it is necessary to have a rating scale constructed for both MRI and CT . We have developed and evaluated a new scale and studied ARWMC in a large number of patients examined with both MRI and CT .  Methods — Seventy-seven patients with ARWMC on either CT or MRI were recruited and a complementary examination ( MRI or CT ) performed . The patients came from 4 centers in Europe , and the scans were rated by 4 raters on 1 occasion with the new ARWMC rating scale . The interrater reliability was evaluated by using & kgr ; statistics . The degree and distribution of ARWMC in CT and MRI scans were compared in different brain areas . Results — Interrater reliability was good for MRI ( & kgr;=0.67 ) and moderate for CT ( & kgr;=0.48 ) . MRI was superior in detection of small ARWMC , whereas larger lesions were detected equally well with both CT and MRI . In the parieto-occipital and infratentorial areas , MRI detected significantly more ARWMC than did CT . In the frontal area and basal ganglia , no differences between modalities were found . When a fluid-attenuated inversion recovery sequence was used , MRI detected significantly more lesions than CT in frontal and parieto-occipital areas . No differences were found in basal ganglia and infratentorial areas . Conclusions — We present a new ARWMC scale applicable to both CT and MRI that has almost equal sensitivity , except for certain regions . The interrater reliability was slightly better for MRI , as was the detectability of small lesions Background Older adults free of dementia but with subjective memory complaints ( SMC ) or mild cognitive impairment ( MCI ) are considered at increased risk of cognitive decline . Vascular risk factors ( VRF ) , including hypertension , heart disease , smoking , hypercholesterolemia and lack of physical activity ( PA ) have been identified as modifiable risk factors contributing to cognitive decline , and white matter hyperintensities ( WMH ) are associated with VRF , SMC and cognitive impairment . Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function , but few studies are investigating these benefits in high-risk population s. The aim of AIBL Active is to determine whether a 24-month physical activity program can delay the progression of white matter changes on magnetic resonance imaging ( MRI ) . Methods / design This single-blind r and omized controlled trial ( RCT ) is offered to 156 participants , aged 60 and older , in the Melbourne arm of the Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging ( AIBL ) . Participants must have SMC with or without MCI and at least one VRF . The PA intervention is a modification of the intervention previously trialed in older adults with SMC and MCI ( Fitness for the Ageing Brain Study ) . It comprises 24 months of moderate , home-based PA ( 150 minutes per week ) and a behavioral intervention package . The primary outcome measure will be change in WMH after 24 months on MRI . Cognition , quality of life , functional fitness , level of physical activity , plasma biomarkers for cerebrovascular disease and amyloid positron emission tomography ( PET ) imaging comprise secondary measures . Discussion Currently , there is no effective pharmacological treatment available to delay cognitive decline and dementia in older adults at risk . Should our findings show that physical activity can slow down the progression of WMH , this RCT would provide an important proof of concept . Since imbedded in AIBL this RCT will also be able to investigate the interaction between vascular and Alzheimer 's disease pathologies . Trial Registration Australia New Zeal and Clinical Trials Registry A growing body of research indicates benefits of cognitive training in older adults , but the neuronal mechanisms underlying the effect of cognitive intervention remains largely unexplored . Neuroimaging methods are sensitive to subtle changes in brain structure and show potential for enhancing our underst and ing of both aging- and training-related neuronal plasticity . Specifically , studies using diffusion tensor imaging ( DTI ) suggest substantial changes in white matter ( WM ) in aging , but it is not known whether cognitive training might modulate these structural alterations . We used tract-based spatial statistics ( TBSS ) optimized for longitudinal analysis to delineate the effects of 8 weeks intensive memory training on WM microstructure . 41 participants ( mean age 61 years ) matched for age , sex and education were r and omly assigned to an intervention or control group . All participants underwent MRI-scanning and neuropsychological assessment  s at the beginning and end of the study . Longitudinal analysis across groups revealed significant increase in frontal mean diffusivity ( MD ) , indicating that DTI is sensitive to WM structural alterations over a 10-week interval . Further , group analysis demonstrated positive effects of training on the short-term changes . Participants in the training group showed a relative increase in fractional anisotropy ( FA ) compared with controls . Further , a significant relationship between memory improvement and change in FA was found , suggesting a possible functional significance of the reported changes . The training effect on FA seemed to be driven by a relative decrease in radial diffusivity , which might indicate a role for myelin-related processes in WM plasticity Abstract Non-demented community-dwelling older adults aged 70–90 years ( n = 1,037 ) r and omly recruited from the electoral roll completed neuropsychological and medical assessment s over six years . The overall prevalence of mild cognitive impairment ( MCI ) at baseline was 36.7 % . Risk factors for MCI include APOE ϵ4 allele carrier status , high homocysteine , heart disease , poor odour identification , low visual acuity and low mental activity , but notable age and sex differences were observed . Neuropsychiatric symptoms were rare ; depression was the most common and was associated with cognitive impairment in at least one domain as well as subsequent dementia 2 years later . Poorer cognitively dem and ing functional abilities were associated with cognitive impairment . Biomarkers for cognitive impairment and decline were identified . Inflammatory markers and plasma apolipoprotein levels were associated with poorer performance in the attention/processing speed domain . Measures of white matter lesions , white matter integrity , sulcal morphology and tractography were identified as novel biomarkers of early cognitive decline . Stronger deactivation in the posteromedial cortex with increasing memory load on functional MRI predicted future decline . Compared to previous reports , our prevalence rates of MCI were higher but rates of progression to dementia and reversion to normal were similar , as were risk factors for progression to dementia 
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RESULTS Our review shows that 1 ) WM abnormality was identified between different subtypes of MCI and healthy controls on diffusion imaging ; 2 ) neither visual ratings of WML nor its volumetry differentiate different subtypes of MCI or its prognosis to dementia ; and 3 ) cognitive correlates of WML were evident in the Amnestic-type MCI in the domains of memory , language , psychomotor speed , attention and executive functions .
CONCLUSION Cognitive reserve and the plasticity of white matter may modulate the impact of WML on the manifestation of the neurodegenerative disease .