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Previous studies have reported bilingualism to be a proxy of cognitive reserve (CR) based on evidence that bilinguals express dementia symptoms ~ 4 years later than monolinguals yet present with greater neuropathology at time of diagnosis when clinical levels are similar. The current study provides new evidence supporting bilingualism's contribution to CR using a novel brain health matching paradigm. Forty cognitively normal bilinguals with diffusion-weighted magnetic resonance images recruited from the community were matched with monolinguals drawn from a pool of 165 individuals in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. White matter integrity was determined for all participants using fractional anisotropy, axial diffusivity, and radial diffusivity scores. Propensity scores were obtained using white matter measures, sex, age, and education as predictive covariates, and then used in one-to-one matching between language groups, creating a matched sample of 32 participants per group. Matched monolinguals had poorer clinical diagnoses than that predicted by chance from a theoretical null distribution, and poorer cognitive performances than matched bilinguals as measured by scores on the MMSE. The findings provide support for the interpretation that bilingualism acts as a proxy of CR such that monolinguals have poorer clinical and cognitive outcomes than bilinguals for similar levels of white matter integrity even before clinical symptoms appear.

A history of depression is a risk factor for dementia. Despite strong epidemiologic evidence, the pathways linking depression and dementia remain unclear. We assessed structural brain alterations in white and gray matter of frontal-executive and corticolimbic circuitries in five groups of older adults putatively at-risk for developing dementia- remitted depression (MDD), non-amnestic MCI (naMCI), MDD+naMCI, amnestic MCI (aMCI), and MDD+aMCI. We also examined two other groups: non-psychiatric (“healthy”) controls (HC) and individuals with Alzheimer’s dementia (AD). Magnetic resonance imaging (MRI) data were acquired on the same 3T scanner. Following quality control in these seven groups, from diffusion-weighted imaging (n = 300), we compared white matter fractional anisotropy (FA), mean diffusivity (MD), and from T1-weighted imaging (n = 333), subcortical volumes and cortical thickness in frontal-executive and corticolimbic regions of interest (ROIs). We also used exploratory graph theory analysis to compare topological properties of structural covariance networks and hub regions. We found main effects for diagnostic group in FA, MD, subcortical volume, and cortical thickness. These differences were largely due to greater deficits in the AD group and to a lesser extent aMCI compared with other groups. Graph theory analysis revealed differences in several global measures among several groups. Older individuals with remitted MDD and naMCI did not have the same white or gray matter changes in the frontal-executive and corticolimbic circuitries as those with aMCI or AD, suggesting distinct neural mechanisms in these disorders. Structural covariance global metrics suggested a potential difference in brain reserve among groups.

Mild cognitive impairment (MCI) of the amnestic type is considered to be a transitionary stage between healthy aging and Alzheimer’s disease (AD). Previous studies have demonstrated that intrinsic functional connectivity of the default network (DN) is altered in normal aging and AD and impacts both within and between network connectivity. While changes within the DN have been reported in MCI, it remains uncertain how interactions with other large-scale brain networks are altered in this prodromal stage of AD. We investigated within and between network connectivity in healthy older adults (HOAs) and older adults with MCI across three canonical brain networks: DN, dorsal attention network, and frontoparietal control network. We also assessed how patterns of functional connectivity among the three networks predicted cognitive status and age using multivariate partial least squares. A total of 91 MCI and 71 HOA restingstate scans were analyzed from the Alzheimer’s Disease Neuroimaging Initiative. There were three key findings. First, a circumscribed pattern of greater between network and interhemispheric connectivity was associated with higher cognitive status in HOAs. Second, for individuals with MCI, cognitive status was positively associated with a more distributed, less differentiated pattern of intrinsic functional connectivity across the three networks. Finally, greater within network functional connectivity was positively associated with cognitive status for HOAs irrespective of age, however this compensation-like effect diminished with increasing age for MCI participants. While reliable differences between healthy aging and MCI in the intrinsic network architecture of the brain are apparent, these differences emerge as shifting associations between network interactivity, cognitive functioning and age.

Standardized neuropsychological tests are routinely used as diagnostic criteria in aging populations and are an important piece of evidence for the identification of clinical pathology and neurodegenerative conditions such as Alzheimer's disease. Tests include such measures as the Mini Mental Status Exam, Delis-Kaplan Executive Function System, Montreal Cognitive Assessment, and others. These tests cover a range of functions including working memory, verbal fluency, prospective memory, and task switching. Interpretation of test results is based on comparison of the participant's score to standard scores that have been normed on a population database. However, a growing body of research has shown that the skills underlying these tests may be significantly different in monolingual and bilingual older adults, especially for those experiencing cognitive impairment, yet the standardized test scores do not account for such differences. Therefore, results of neuropsychological tests may be different for bilingual populations than for monolinguals, and those differences may be misinterpreted. The issue is important because the consequences of these interpretative errors may be over- or under-diagnosis of cognitive impairment. The present study examined the neuropsychological test scores of monolingual and bilingual older adults who were experiencing healthy aging or cognitive impairment to establish patterns in these scores that can more accurately guide the interpretation for bilingual older adults by considering group differences in the underlying abilities.

Here, we review the neural correlates of cognitive control associated with bilingualism. We demonstrate that lifelong practice managing two languages orchestrates global changes to both the structure and function of the brain. Compared with monolinguals, bilinguals generally show greater gray matter volume, especially in perceptual/motor regions, greater white matter integrity, and greater functional connectivity between gray matter regions. These changes complement electroencephalography findings showing that bilinguals devote neural resources earlier than monolinguals. Parallel functional findings emerge from the functional magnetic resonance imaging literature: bilinguals show reduced frontal activity, suggesting that they do not need to rely on top-down mechanisms to the same extent as monolinguals. This shift for bilinguals to rely more on subcortical/posterior regions, which we term the bilingual anterior-to-posterior and subcortical shift (BAPSS), fits with results from cognitive aging studies and helps to explain why bilinguals experience cognitive decline at later stages of development than monolinguals.

Testing older adults in the morning generally improves behavioral performance relative to afternoon testing. Morning testing is also associated with brain activity similar to that of young adults. Here, we used graph theory to explore how time of day (TOD) affects the organization of brain networks in older adults across rest and task states. We used nodes from the automated anatomical labeling atlas to construct participant-specific correlation matrices of fMRI data obtained during 1-back tasks with interference and rest. We computed pairwise group differences for key graph metrics, including small-worldness and modularity. We found that older adults tested in the morning and young adults did not differ on any graph metric. Both of these groups differed from older adults tested in the afternoon during the tasks—but not rest. Specifically, the latter group had lower modularity and small-worldness (indices of more efficient network organization). Across all groups, higher modularity and small-worldness strongly correlated with reduced distractibility on an implicit priming task. Increasingly, TOD is seen as important for interpreting and reproducing neuroimaging results. Our study emphasizes how TOD affects brain network organization and executive control in older adults.

We investigated sex differences in the association between a measure of physical health, cardiorespiratory fitness (CRF), and brain function using resting-state functional connectivity fMRI. We examined these sex differences in the default, frontoparietal control, and cingulo-opercular networks, assemblies of functionally connected brain regions known to be impacted by both age and fitness level. Healthy older adults ( n = 49; 29 women) were scanned to obtain measures of intrinsic connectivity within and across these 3 networks. We calculated global efficiency (a measure of network integration) and local efficiency (a measure of network specialization) using graph theoretical methods. Across all three networks combined, local efficiency was positively associated with CRF, and this was more robust in male versus female older adults. Furthermore, global efficiency was negatively associated with CRF, but only in males. Our findings suggest that in older adults, associations between brain network integrity and physical health are sex-dependent. These results underscore the importance of considering sex differences when examining associations between fitness and brain function in older adulthood. NEW & NOTEWORTHY We examined the association between cardiorespiratory fitness and resting state functional connectivity in several brain networks known to be impacted by age and fitness level. We found significant associations between fitness and measures of network integration and network specialization, but in a sex-dependent manner, highlighting the interplay between sex differences, fitness, and aging brain health. Our findings underscore the importance of considering sex differences when examining associations between fitness and brain function in older adulthood.