Imaging and neuropsychological correlates of white matter lesions in different subtypes of Mild Cognitive Impairment: A systematic review

BACKGROUND:White matter lesions (WML) are prevalent in older adults. The association between WML and cognition in different subtypes of Mild Cognitive Impairment (MCI) is inconsistent in the literature.OBJECTVES:We aim to provide a systematic review on the impact of WML in different subtypes of MCI, and discuss the recent findings on white matter plasticity.METHODS:We reviewed peer-reviewed articles from January 2011 to August 2016 and identified 12 studies investigating the association between WML and subtypes of MCI with both neuroimaging and cognitive measures.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. Further research is needed to study the plasticity of white matter in the MCI population to evaluate its potential clinical application

Hemispheric differences between left and right supramarginal gyrus for pitch and rhythm memory

Functional brain imaging studies and non-invasive brain stimulation methods have shown the importance of the left supramarginal gyrus (SMG) for pitch memory. The extent to which this brain region plays a crucial role in memory for other auditory material remains unclear. Here, we sought to investigate the role of the left and right SMG in pitch and rhythm memory in non-musicians. Anodal or sham transcranial direct current stimulation (tDCS) was applied over the left SMG (Experiment 1) and right SMG (Experiment 2) in two different sessions. In each session participants completed a pitch and rhythm recognition memory task immediately after tDCS. A significant facilitation of pitch memory was revealed when anodal stimulation was applied over the left SMG. No significant effects on pitch memory were found for anodal tDCS over the right SMG or sham condition. For rhythm memory the opposite pattern was found; anodal tDCS over the right SMG led to an improvement in performance, but anodal tDCS over the left SMG had no significant effect. These results highlight a different hemispheric involvement of the SMG in auditory memory processing depending on auditory material that is encoded

Mobility in aging : clinical and neuroimaging studies

Introduction: The world’s population is aging at an unprecedented rate. By 2050, the number of adults older than 60 years will double from 10% to 20%. This trend has immense implications, due to the prevalence of impaired physical and cognitive functions among older adults. Therefore, it is important to understand the underlying mechanisms for these impairments and identify effective prevention strategies. White matter hyperintensities (WMHs) are common findings on MRI scans of older adults, and are associated with both physical and cognitive decline. Key risk factors for WMHs are related to metabolic and cardiovascular health. Thus, due to the established and significant benefit of targeted exercise training on metabolic and cardiovascular health in older adults, we hypothesized that one mechanism by which exercise, and specifically resistance training (RT), promotes physical and cognitive functions is by reducing WMH progression among older adults. Methods: We explored the associations between WMHs and physical and cognitive functions in Chapters 2 to 4. In Chapter 5, we presented a randomized controlled trial of 52-week RT. Participants were randomized to either once-weekly RT, twice-weekly RT, or twice-weekly balance and tone. We investigated the effect of RT on WMH progression. Results: Results from Chapters 2 and 3 suggest that reduced WMH progression may translate to maintained, or improved, physical and cognitive functions. Chapter 4 demonstrated that physical function is important for cognitive health. Chapter 5 provided proof-of-concept evidence that RT has beneficial effects on WMH progression, which may translate to improved physical and cognitive function. Specifically, we found that reduced WMH progression was significantly iii associated with improved gait speed. Moreover, our results suggest this effect may be dose-dependent, as the significant reduction in WMH progression was only observed among those in the twice-weekly RT group, and not in the once-weekly RT group. Conclusion: We provided converging evidence from four separate studies leading to the conclusion that RT has beneficial effects on WMH progression. Since WMHs are demonstrated to have significant associations with physical and cognitive dysfunctions, we believe that exercise-induced reductions of WMHs progression might translate to improvements in physical and cognitive functions in older adults.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat

The association between cognitive function and white matter lesion location in older adults: a systematic review

Background: Maintaining cognitive function is essential for healthy aging and to function autonomously within society. White matter lesions (WMLs) are associated with reduced cognitive function in older adults. However, whether their anatomical location moderates these associations is not well-established. This review systematically evaluates peer-reviewed evidence on the role of anatomical location in the association between WMLs and cognitive function. Methods: In accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement, databases of EMBASE, PUBMED, MEDLINE, and CINAHL, and reference lists of selected papers were searched. We limited our search results to adults aged 60 years and older, and studies published in the English language from 2000 to 2011. Studies that investigated the association between cognitive function and WML location were included. Two independent reviewers extracted: 1) study characteristics including sample size, sample characteristic, and study design; 2) WML outcomes including WML location, WML quantification method (scoring or volume measurement), strength of the MRI magnet in Tesla, and MRI sequence used for WML detection; and 3) cognitive function outcomes including cognitive tests for two cognitive domains of memory and executive function/processing speed. Results: Of the 14 studies included, seven compared the association of subcortical versus periventricular WMLs with cognitive function. Seven other studies investigated the association between WMLs in specific brain regions (e.g., frontal, parietal lobes) and cognitive function. Overall, the results show that a greater number of studies have found an association between periventricular WMLs and executive function/processing speed, than subcortical WMLs. However, whether WMLs in different brain regions have a differential effect on cognitive function remains unclear. Conclusions: Evidence suggests that periventricular WMLs may have a significant negative impact on cognitive abilities of older adults. This finding may be influenced by study heterogeneity in: 1) MRI sequences, WML quantification methods, and neuropsychological batteries; 2) modifying effect of cardiovascular risk factors; and 3) quality of studies and lack of sample size calculation.Arts, Faculty ofPhysical Therapy, Department ofPsychology, Department ofRadiology, Department ofMedicine, Faculty ofReviewedFacult