The functional connectivity of language network across the life span: Disentangling the effects of typical aging from Alzheimer's disease.

Language is usually characterized as the most preserved cognitive function during typical aging. Several neuroimaging studies have shown that healthy aging is characterized by inter-network compensation which correlates with better language performance. On the contrary, language deficits occur early in the course of Alzheimer's disease (AD). Therefore, this study compares young participants, healthy older participants, and prodromal AD participants, to characterize functional connectivity changes in language due to healthy aging or prodromal AD. We first compared measures of integrated local correlations (ILCs) and fractional amplitude of low-frequency oscillations (fALFFs) in language areas. We showed that both groups of older adults had lower connectivity values within frontal language-related areas. In the healthy older group, higher integrated local correlation (ILC) and fALFF values in frontal areas were positively correlated with fluency and naming tasks. We then performed seed-based analyses for more precise discrimination between healthy aging and prodromal AD. Healthy older adults showed no functional alterations at a seed-based level when the seed area was not or only slightly impaired compared to the young adults [i.e., inferior frontal gyrus (IFG)], while prodromal AD participants also showed decreased connectivity at a seed-based level. On the contrary, when the seed area was similarly impaired in healthy older adults and prodromal AD participants on ILC and fALFF measures, their connectivity maps were also similar during seed-to-voxel analyses [i.e., superior frontal gyrus (SFG)]. Current results show that functional connectivity measures at a voxel level (ILC and fALFF) are already impacted in healthy aging. These findings imply that the functional compensations observed in healthy aging depend on the functional integrity of brain areas at a voxel level.

Language Network Connectivity Increases in Early Alzheimer's Disease.

BACKGROUND: Language production deficits occur early in the course of Alzheimer's disease (AD); however, only a few studies have focused on language network's functional connectivity in mild cognitive impairment (MCI) due to AD. OBJECTIVE: The current study aims to uncover the extent of language alteration at the MCI stage, at a behavioral and neural level, using univariate and multivariate analyses of structural MRI and resting-state fMRI. METHODS: Twenty-four MCI due to AD participants and 24 matched healthy controls underwent a comprehensive language evaluation, a structural T1-3D MRI, and resting-state fMRI. We performed seed-based analyses, using the left inferior frontal gyrus and left posterior temporal gyrus as seeds. Then, we analyzed connectivity between executive control networks and language network in each group. Finally, we used multivariate pattern analyses to test whether the two groups could be distinguished based on the pattern of atrophy within the language network; within the executive control networks, as well as the pattern of functional connectivity within the language network and within the executive control networks. RESULTS: MCI due to AD participants had language impairment during standardized language tasks and connected-speech production. Regarding functional connectivity, univariate analyses were not able to discriminate participants, while multivariate pattern analyses could significantly predict participants' group. Language network's functional connectivity could discriminate MCI due to AD participants better than executive control networks. Most notably, they revealed an increased connectivity at the MCI stage, positively correlated with language performance. CONCLUSION: Multivariate analyses represent a useful tool for investigating the functional and structural (re-)organization of the neural bases of language.

Increased functional connectivity supports language performance in healthy aging despite gray matter loss.

Although language is quite preserved from aging, it remains unclear whether age-related differences lead to a deterioration or reorganization in language functional networks, or to different dynamics with other domains (e.g., the multiple-demand system). The present study is aimed at examining language networks, using resting-state functional magnetic resonance imaging in typical aging in relation to language performance. Twenty-three (23) younger adults and 24 healthy older adults were recruited. Volumetric gray matter differences between the 2 groups were assessed using voxel-based morphometry. Then, seed-based analyses, integrated local correlations in core regions of the language network, and within- and between-network connectivity were performed. We expected less extended connectivity maps, local coherence diminution, and higher connectivity with the multiple-demand system in older adults. On the contrary, analyses showed language network differences in healthy aging (i.e., increased connectivity with areas inside and outside language network), but no deterioration, despite widespread atrophy in older adults. Integrated local correlation revealed alterations that were unnoticeable with other analyses. Although gray matter loss was not correlated with language performance, connectivity differences were positively correlated with fluency performance in the older group. These results differ from the literature concerning other cognitive networks in aging in that they show extra internetwork connections without a decrease in intranetwork language connections. This reorganization could explain older adults' good language performance and could be interpreted in accordance with the scaffolding theory of aging and cognition.

Posterior Cortical Atrophy: Does Complaint Match the Impairment? A Neuropsychological and FDG-PET Study.

Objective: Posterior Cortical Atrophy (PCA) is a neurodegenerative disease characterized predominantly by visual impairment. However, diagnosis of PCA remains complicated with an interval of several years between initial reporting of symptoms and diagnosis. The aim of the present study is to define if patients' visual and gestural complaints are consistent with their clinical profile. Method: An evaluation of daily visual problems as well as a full neuropsychological assessment and FDG-PET were performed in 15 PCA patients. We compared glucose metabolism between these PCA patients and 18 healthy controls. Correlation analyses were conducted in PCA patients between visual and gestural complaint, clinical impairments, and brain glucose metabolism. Results: Major impairment of cognitive functions was detected in PCA patients specifically in visual domains. Positive correlations were found between visual impairments and hypometabolism in the right temporo-parieto-occipital cortices. However, no correlation was found between complaint and visual impairment in PCA patients. Discussion: Our main results suggest a consistent relationship between clinical impairment and brain metabolism. However, the patient's complaint and visual performance are not linked. Combining the literature and our results, it seems that patients are generally aware of difficulties but misinterpret them. This misinterpretation may be responsible for the delayed diagnosis.

Involvement of the Cingulate Cortex in Anosognosia: A Multimodal Neuroimaging Study in Alzheimer's Disease Patients.

BACKGROUND: Anosognosia is a frequent symptom of Alzheimer's disease (AD), but its neural substrates remain in question. OBJECTIVE: In this study, we combined neuroimaging with a neuropsychological evaluation to assess neural substrates of anosognosia. METHODS: We prospectively recruited 30 patients with probable early-stage AD and matched healthy controls. Participants underwent MRI, FDG-PET, and a neuropsychological evaluation that includes an assessment of anosognosia. In the AD group, correlations between the anosognosia score, neuroimaging modalities, and neuropsychological performance were performed. RESULTS: Atrophy and hypometabolism were correlated with the anosognosia score in the left dorsal anterior cingulate cortex. The anosognosia score was also correlated with atrophy of the cerebellar vermis, the left postcentral gyrus, and the right fusiform gyrus. No relation was found between anosognosia and the neuropsychological assessment. DISCUSSION: Structural and metabolic alteration in the dorsal anterior cingulate cortex seems to be associated with a diminution of awareness in patients with early-stage AD.