No statistically significant interactions were noted between bilingualism and MMSE on brain structure. No other brain structures showed statistically significant relationships with bilingualism or MMSE, including the hippocampus. Also, the monolingual group did not show any statistically significant higher regional brain volumes on MRI compared to the bilingual group. Also, there was no correlation between left versus right hippocampal asymmetry or temporal lobe asymmetry.
In this study, we have demonstrated that for a comparable level of cognitive impairment, bilinguals with AD demonstrated multiple increased regional brain volumes compared to monolinguals with AD.
These brain regions may function as neural correlates for increased resistance for AD pathology in bilingualism. Additionally, the results suggest that bilingualism has potential as a preventive strategy for AD given its relation to larger brain volume correlates of cognitive reserve.
Prior studies of normal individuals have suggested structural and functional changes in bilingualism in language areas and their related connections. Several studies have shown increased gray matter volume in cognitively-normal bilinguals especially left hemisphere frontal regions and their connections for language functions and language control [7, 17, 18].
Bilinguals have more gray and white matter in some areas compared to monolinguals
Compared to normal monolinguals, normal bilinguals have more gray matter in these areas, particularly left inferior frontal gyrus, and greater frontal white matter tracts [19, 20]. Normal bilinguals compared to normal monolinguals have more white matter in the corpus callosum, the inferior and superior longitudinal (L >R) fasciculi, and other white matter tracts, especially with L2 proficiency and immersion [21, 22]. Early-acquired, proficient bilinguals have increased structural and functional connectivity between inferior frontal gyrus and regions of the brain supporting language control such as the salience and frontoparietal networks, between white matter regions mediating connectivity in nonverbal executive control tasks, and between right and left inferior frontal gyri [23, 24]. Long-term structural changes in gray and white matter connectivity, may also occur when the second language is acquired relatively late in life [19, 20].
In contrast to relatively preserved language areas and their related connections, when bilinguals develop dementia or AD, they may have greater mesiotemporal neuropathology or hypometabolism at comparable levels of functional clinical impairment [24, 25]. One of these studies compared monolingual (34 MCI; 13 AD) with multilingual (34 MCI; 13 AD) patients and found higher tissue densities in medial temporal areas in the multilingual MCI group, but similar or lower in the multilingual AD group . However, in language and language control areas, both of the multilingual groups had thicker cortex than the monolingual groups [25, 26]. Our results add to these findings, indicating that key subcortical areas are also better preserved among AD patients who speak more than one language compared to those who only speak one.
The advantages of this study were a characterized bilingual and monolingual AD cohort, matched for age of presentation and general cognitive impairment, with automated volumetrics that assessed regions not typically evaluated such as the ventral diencephalon.
The ventral diencephalon has been previously implicated in neurodegeneration and cognitive reserve  and this structure includes the mammillary bodies that are part of hippocampal circuitry and has connections to the nucleus basalis of Meynert of the basal forebrain. The implication of the brainstem as increased in bilingualism is also relevant to AD pathogenesis given its inclusion of the locus coeruleus that also been implicated in early AD neuropathology . Disadvantages and thus topics for future studies include inclusion of functional imaging sequences and longitudinal data on cognitive decline.
The degree of brain atrophy in individuals ‘matched’ for cognitive decline remains controversial and an area of active research. Several studies have found that among ‘matched’ individuals, the group with greater cognitive reserve, bilingual cohorts included, have greater brain atrophy for the same degree of cognitive decline [2, 29]. These differences in the studies may be due to the fact that the protective effect of cognitive reserve rapidly declines with greater degree of brain atrophy resulting in rapid deterioration after a ‘tipping point’ . Additional topics for future directions can be to engage in amyloid and tau PET imaging as well as imaging of synaptic vesicles as different molecular imaging metrics of AD pathology and cognitive reserve. Hippocampal subfield segmentation as well as segmentation of language areas are also other approaches of possible future analyses. Overall, this study lends insight with quantitative brain MRI into novel neural correlates of higher cognitive reserve in bilinguals with AD.
In conclusion, this study adds to the literature on differences in brain structures between bilingual and monolingual patients with AD. In addition to the literature on greater mesiotemporal impairment at comparable levels of dementia, there may be relative preservation of critical subcortical structures, along with language areas and their connections, consistent with improved neural reserve with bilingualism.
Future studies of neuroimaging in these patients are needed to further clarify the neuroimaging structures that mediate neural reserve and the effects of bilingualism in delaying the onset of the clinicalsymptoms of AD.
Supported by McLoughlin Cognitive Health Gift Fund and the Pituitary Injury Foundation. Dr. Raji is supported in his research by grants from the WUSTL NIH KL2 Grant (KL2 TR000450 – ICTS Multidisciplinary Clinical Research Career Development Program), the Radiological Society of North America Research Scholar Grant and the Foundation of the American Society of Neuroradiology Boerger Research Fund for Alzheimer’s Disease and Neurocognitive Disorders. Dr. Mendez is PI on US National Institute on Aging Grant 1RF1AG050967.
Authors’ disclosures available online (https://www.j-alz.com/manuscript-disclosures/20-0200r2).
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