Maxime Montembeault

The impact of aging on gray matter structural covariance networks

Previous anatomical volumetric studies have shown that healthy aging is associated with gray matter tissue loss in specific cerebral regions. However, these studies may have potentially missed critical elements of age-related brain changes, which largely exist within interrelationships among brain regions. This magnetic resonance imaging research aims to assess the effects of aging on the organization of gray matter structural covariance networks. Here, we used voxel-based morphometry on high-definition brain scans to compare the patterns of gray matter structural covariance networks that sustain different sensorimotor and high-order cognitive functions among young (n=88, mean age=23.5±3.1 years, female/male=55/33) and older (n=88, mean age=67.3±5.9 years, female/male=55/33) participants. This approach relies on the assumption that functionally correlated brain regions show correlations in gray matter volume as a result of mutually trophic influences or common experience-related plasticity. We found reduced structural association in older adults compared with younger adults, specifically in high-order cognitive networks. Major differences were observed in the structural covariance networks that subserve the following: a) the language-related semantic network, b) the executive control network, and c) the default-mode network. Moreover, these cognitive functions are typically altered in the older population. Our results indicate that healthy aging alters the structural organization of cognitive networks, shifting from a more distributed (in young adulthood) to a more localized topological organization in older individuals.

Altered Gray Matter Structural Covariance Networks in Early Stages of Alzheimer's Disease

Clinical symptoms observed in Alzheimers disease (AD) patients may reflect variations within specific large-scale brain networks, modeling AD as a disconnection syndrome. The present magnetic resonance imaging study aims to compare the organization of gray matter structural covariance networks between 109 cognitively unimpaired controls (CTRL) and 109 AD patients positive to beta-amyloid at the early stages of the disease, using voxel-based morphometry. The default-mode network (DMN; medial temporal lobe subsystem) was less extended in AD patients in comparison with CTRL, with a significant decrease in the structural association between the entorhinal cortex and the medial prefrontal and the dorsolateral prefrontal cortices. The DMN (midline core subsystem) was also less extended in AD patients. Trends toward increased structural association were observed in the salience and executive control networks. The observed changes suggest that early disruptions in structural association between heteromodal association cortices and the entorhinal cortex could contribute to an isolation of the hippocampal formation, potentially giving rise to the clinical hallmark of AD, progressive memory impairment. It also provides critical support to the hypothesis that the reduced connectivity within the DMN in early AD is accompanied by an enhancement of connectivity in the salience and executive control networks.

Atrophy in Alzheimer’s Disease and Semantic Dementia: An ALE Meta-Analysis of Voxel-Based Morphometry Studies

BACKGROUND/OBJECTIVES Alzheimers disease (AD) and semantic dementia (SD) have distinct episodic memory profiles despite the hippocampal atrophy that characterizes both diseases. The aim of this study was to delineate the pattern of gray matter (GM) atrophy associated with AD and SD as well as any differences in these patterns by pooling together the results of previous voxel-based morphometry (VBM) studies.Methods/Overview: We conducted a meta-analysis of VBM studies that investigated GM atrophy in AD patients versus controls (CTRLs) and in SD patients versus CTRLs using the activation likelihood estimation (ALE) approach. Our systematic review allowed us to identify 63 VBM studies. RESULTS The results confirmed that in addition to the classical cortical pattern of atrophy involving posterior medial and lateral regions in AD and the anterior lateral temporal lobes in SD, both AD and SD patients are characterized by bilateral atrophy of the hippocampus. Furthermore, in SD, the hippocampal atrophy was limited to the anterior portion of the hippocampus, while in AD, both the anterior and posterior parts of the hippocampus exhibited atrophy. When we compared the foci identified in the studies that compared AD patients versus CTRLs with those identified in the studies that compared SD patients versus CTRLs, we observed that the atrophy in the posterior hippocampus and precuneus was more severe in AD. CONCLUSION These results support theories that propose that the deficits observed in AD result from damage to the episodic memory network, which involves the posterior hippocampus and posterior medial brain regions. However, sparing of the posterior hippocampus in SD could explain the absence of episodic memory deficits in this population.

Naming unique entities in the semantic variant of primary progressive aphasia and Alzheimer's disease: Towards a better understanding of the semantic impairment

ABSTRACT While the semantic variant of primary progressive aphasia (svPPA) is characterized by a predominant semantic memory impairment, episodic memory impairments are the clinical hallmark of Alzheimers disease (AD). However, AD patients also present with semantic deficits, which are more severe for semantically unique entities (e.g. a famous person) than for common concepts (e.g. a beaver). Previous studies in these patient populations have largely focused on famous‐person naming. Therefore, we aimed to evaluate if these impairments also extend to other semantically unique entities such as famous places and famous logos. In this study, 13 AD patients, 9 svPPA patients, and 12 cognitively unimpaired elderly subjects (CTRL) were tested with a picture‐naming test of non‐unique entities (Boston Naming Test) and three experimental tests of semantically unique entities assessing naming of famous persons, places, and logos. Both clinical groups were overall more impaired at naming semantically unique entities than non‐unique entities. Naming impairments in AD and svPPA extended to the other types of semantically unique entities, since a CTRL>AD>svPPA pattern was found on the performance of all naming tests. Naming famous places and famous persons appeared to be most impaired in svPPA, and both specific and general semantic knowledge for these entities were affected in these patients. Although AD patients were most significantly impaired on famous‐person naming, only their specific semantic knowledge was impaired, while general knowledge was preserved. Post‐hoc neuroimaging analyses also showed that famous‐person naming impairments in AD correlated with atrophy in the temporo‐parietal junction, a region functionally associated with lexical access. In line with previous studies, svPPA patients’ impairment in both naming and semantic knowledge suggest a more profound semantic impairment, while naming impairments in AD may arise to a greater extent from impaired lexical access, even though semantic impairment for specific knowledge is also present. These results highlight the critical importance of developing and using a variety of semantically‐unique‐entity naming tests in neuropsychological assessments of patients with neurodegenerative diseases, which may unveil different patterns of lexical‐semantic deficits. HIGHLIGHTSFamous‐person naming was specifically impaired in AD patients.Both famous‐person and ‐place naming were specifically impaired in svPPA patients.General and specific semantic knowledge was impaired in svPPA, but general knowledge was preserved in AD.svPPA patients’ impairment in naming and knowledge suggest a profound semantic impairment.Naming impairments in AD may arise to a greater extent from impaired lexical access.

Loss of person-specific knowledge in Alzheimer’s disease: Evidence from priming

Semantic deficits in Alzheimer’s disease (AD) are often more severe for items that are characterized by a unique semantic and lexical association, such as famous people. Whether these deficits are due to the degradation of semantic information or a deficit in the ability to intentionally access semantic knowledge remains controversial. To assess the integrity of the semantic system without explicitly accessing it, a priming paradigm was used. Semantic and repetition priming effects in individuals with AD (n = 7) and age-matched controls (n = 13) were measured in a familiarity judgment task using visually-presented names of famous people. A defective priming effect in AD subjects was observed in the semantic priming but not in the repetition priming condition. Therefore, the semantic impairments observed in AD may indicate a degraded representation of the semantic information concerning famous people.

Proper name anomia in poststroke aphasics: evidence from a multiple-case study

We aimed to characterize difficulties in famous face naming in three poststroke aphasic patients with a lesion limited to the left mid-posterior temporal language regions, sparing the anterior temporal lobe. The patients did not present semantic deficits specific to known people. Nonetheless, they showed difficulties naming famous buildings in addition to famous faces, but they were comparable to healthy controls in generating proper names. Our results support the critical role of the mid-posterior temporal language regions in the lexical retrieval of proper names, namely from pictorial stimuli, in absence of semantic impairments.

Word reading aloud skills: their positive redefinition through ageing

Background Successful reading can be achieved by means of two different procedures: sub-word processes for the pronunciation of words without semantics or pseudowords (PW) and whole-word processes that recruit word-specific information regarding the pronunciation of words with atypical orthography-to-phonology mappings (exception words, EW). Methods We compared reading abilities between 35 young and 35 older adults in an experimental reading task including low-frequency regular (RW), EW and PW. Results A significant effect of word type, group and an interaction word type by group was found for errors. Young adults made significantly more regularization errors than older subjects for EWs. Conversely, young readers read PW and RW significantly faster. These results indicate that older adults compared with younger adults are more accurate when reading low-frequency EW. Conclusion The fact that young adults were faster than the elderly for PW and RW reading, together with a larger number of regularization errors in EW reading, suggests that they relied on sub-word processes to a larger extent than the older group. Highlights What is already known about this topic: Sub-word processes are based on the use of consistent or regular orthography-to-phonology mappings that represent the sub-units that compose words and are mainly used for pseudoword reading. Whole-word processes use item-specific information regarding the pronunciation of a particular word and are mainly used for exception word reading. During reading acquisition, and as reading experience increase, children switch from sub-word processing strategies to a more efficient use of whole-word processes. What this paper adds: The ability to read exception words continues to improve over the lifespan, even in later stages of life. Elderly adults rely on whole-word processes to a larger extent than younger adults. Implications for theory, policy or practice: These results contrast with the general idea that ageing is associated with general cognitive decline, so older people should be encouraged to engage in reading activities. The fact that this cognitive ability is improved during ageing could provide insightful information for developing intervention programmes in patients with acquired reading disorders.

The Role of the Left Anterior Temporal Lobe for Unpredictable and Complex Mappings in Word Reading

The anterior temporal lobes (ATLs) have been consistently associated with semantic processing which, in turn, has a key role in reading aloud single words. This study aimed to investigate (1) the reading abilities in patients with the semantic variant of primary progressive aphasia (svPPA), and (2) the relationship between gray matter (GM) volume of the left ATL and word reading performance using voxel-based morphometry (VBM). Three groups of participants (svPPA, Alzheimer’s Disease, AD and healthy elderly adults) performed a reading task with exception words, regular words and pseudowords, along with a structural magnetic resonance imaging scan. For exception words, the svPPA group had a lower accuracy and a greater number of regularization errors as compared to the control groups of healthy participants and AD patients. Similarly, for regular words, svPPA patients had a lower accuracy in comparison with AD patients, and a greater number of errors related to complex orthography-to-phonology mappings (OPM) in comparison to both control groups. VBM analyses revealed that GM volume of the left ATL was associated with the number of regularization errors. Also, GM volume of the left lateral ATL was associated with the number of errors with complex OPM during regular word reading. Our results suggest that the left ATL might play a role in the reading of exception words, in accordance with its role in semantic processing. Results further support the involvement of the left lateral ATL in combinatorial processes, including the integration of semantic and phonological information, for both exception and regular words.

Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer’s disease: a behavioral and neuroimaging study

HighlightsComprehension of concrete words was more impaired than that of abstract words in svPPA.Concrete words were not more impaired than abstract words in AD and in healthy older adults.Concrete word comprehension was correlated with atrophy in the left anterior temporal lobe. ABSTRACT The aim of this study was to investigate the comprehension of concrete, abstract and abstract emotional words in semantic variant primary progressive aphasia (svPPA), Alzheimer’s disease (AD), and healthy elderly adults (HE) Three groups of participants (9 svPPA, 12 AD, 11 HE) underwent a general neuropsychological assessment, a similarity judgment task, and structural brain MRI. The three types of words were processed similarly in the group of AD participants. In contrast, patients in the svPPA group were significantly more impaired at processing concrete words than abstract words, while comprehension of abstract emotional words was in between. VBM analyses showed that comprehension of concrete words relative to abstract words was significantly correlated with atrophy in the left anterior temporal lobe. These results support the view that concrete words are disproportionately impaired in svPPA, and that concrete and abstract words may rely upon partly dissociable brain regions.

Brain Structure Covariance Associated with Gait Control in Aging

Background Structural and functional brain imaging methods have identified age-related changes in brain structures involved in gait control. This cross-sectional study aims to investigate gray matter networks associated with gait control in aging using structural covariance analysis. Methods Walking speed were measured in 326 non-demented older community-dwellers (age 71.3±4.5; 41.7% female) under three different walking conditions: normal walking and two challenging tasks: motor (i.e.; fast speed) and an attention-demanding dual task (i.e.; backward counting). Results Three main individual gray matter regions were positively correlated with walking speed (i.e.; slower walking speed was associated with lower brain volumes): right thalamus, right caudate nucleus and left middle frontal gyrus for normal walking, rapid walking and dual-task walking condition, respectively. The structural covariance analysis revealed that prefrontal regions were part of the networks associated with every walking condition; the right caudate was associated specifically with the hippocampus, amygdala and insula for the rapid walking condition and the left middle frontal gyrus with a network involving the cuneus for the dual-task condition. Conclusion Our results suggest that brain networks associated with gait control vary according to walking speed and depend on each walking condition. Gait control in aging involved a distributed network including regions for emotional control that are recruited in challenging walking conditions.