As aging population is increasing, new methodologies to apprehend and enhance the mechanisms related to optimal brain function in advancing age become urgent. This review describes how the combined ...use of non‐invasive brain stimulation (NIBS) with functional magnetic resonance imaging (fMRI) provides novel experimental data on the putative neurophysiological mechanisms underlying inter‐individual differences in cognitive status among older adults, also further illuminating our understanding of theoretical models proposed within the cognitive neuroscience of aging literature. In addition, it explores published evidence of how this combined procedure entails the capacity to modify the activity and connectivity of specific brain networks in older adults, potentially leading to improvements in cognitive function and other measures reflecting mental health status. Although additional research is needed, combining NIBS with fMRI might provide innovative understanding of how fundamental brain plasticity mechanisms operate in advancing age, a knowledge that may be eventually used to refine more individually tailored approaches to promote brain health in aged populations.
Despite the increasing aging population and the high prevalence of OSA in elderly adults, little is known about cognitive effects of OSA and the effectiveness of CPAP treatment. Therefore, this study ...investigated whether elderly patients with OSA present cognitive deficits and functional and structural alterations of the brain that could be improved by CPAP treatment.
This randomized, evaluator-blinded, parallel-group, single-center pilot study involved patients aged ≥ 65 years with newly-diagnosed severe OSA syndrome. Thirty-three patients were assigned to receive either conservative care (CC) or CPAP plus CC for 3 months. At baseline and 3 months after treatment, patients underwent a neuropsychologic evaluation and a functional and structural MRI study of connectivity within the default mode network (DMN) and of cortical thickness.
Neuropsychologic evaluation revealed no differences in cognitive performance between OSA groups at baseline. By contrast, after CPAP treatment, patients showed a significant improvement in episodic (between-group difference in change, 7.60; 95% CI, 1.66-13.55; P = .014) and short-term memory (between-group difference in change, 1.06; 95% CI, 0.10-2.01; P = .032) and in executive function (speed of mental processing, 5.74; 95% CI, 1.69-9.79; P = .007; mental flexibility, -47.64; 95% CI, -81.83 to -13.45; P = .008), whereas no changes were observed in the CC group. Neuroimaging revealed an increase in the connectivity in the right middle frontal gyrus after 3 months of CPAP treatment and a higher percentage of cortical thinning in the CC group. No association was seen between cognition and brain functional connectivity changes within the DMN.
Elderly patients with severe OSA who present with cognitive difficulties could benefit from CPAP treatment. Moreover, CPAP treatment increases the connectivity of the DMN and attenuates cortical thinning.
ClinicalTrials.gov; No.: NCT01826032; URL: www.clinicaltrials.gov.
Abstract White matter (WM) damage has been reported in Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) in diffusion tensor imaging (DTI) studies. It is, however, unknown how the ...investigation of multiple tensor indexes in the same patients, can differentiate them from normal aging or relate to patients cognition. Forty-six individuals (15 healthy, 16 a-MCI and 15 AD) were included. Voxel-based tract based spatial-statistics (TBSS) was used to obtain whole-brain maps of main WM bundles for fractional anisotropy (FA), radial diffusivity (DR), axial diffusivity (DA) and mean diffusivity (MD). FA reductions were evidenced among AD patients with posterior predominance. A-MCI patients displayed reduced mean FA in these critical regions, compared to healthy elders. MD increases were widespread in both groups of patients. Interestingly, a-MCI patients exhibited DR increases in overlapping areas of FA shrinkages in AD, whereas DA increases were only observed in AD. Gray matter atrophy explained most DTI differences, except those regarding MD in both groups as well as DR increases in posterior associative pathways among a-MCI cases. FA values were the only DTI measure significantly related to memory performance among patients. Present findings suggest that most DTI-derived changes in AD and a-MCI are largely secondary to gray matter atrophy. Notably however, specific DR signal increases in posterior parts of the inferior fronto-occipital and longitudinal fasciculi may reflect early WM compromise in preclinical dementia, which is independent of atrophy. Finally, global measures of integrity, particularly orientation coherence (FA) of diffusion, appear to be more closely related to the cognitive profile of our patients than indexes reflecting water movement parallel (DA) and perpendicular (DR) to the primary diffusion direction.
•We assessed intrinsic connectivity of networks underlying cognition in youth.•Evidence of age effects on intrinsic connectivity was found across all networks.•Intrinsic connectivity showed no effect ...of sex, nor age by sex interactions.
There is limited evidence on the effects of age and sex on intrinsic connectivity of networks underlying cognition during childhood and adolescence. Independent component analysis was conducted in 113 subjects aged 7–18; the default mode, executive control, anterior salience, basal ganglia, language and visuospatial networks were identified. The effect of age was examined with multiple regression, while sex and ‘age×sex’ interactions were assessed by dividing the sample according to age (7–12 and 13–18 years). As age increased, connectivity in the dorsal and ventral default mode network became more anterior and posterior, respectively, while in the executive control network, connectivity increased within frontoparietal regions. The basal ganglia network showed increased engagement of striatum, thalami and precuneus. The anterior salience network showed greater connectivity in frontal areas and anterior cingulate, and less connectivity of orbitofrontal, middle cingulate and temporoparietal regions. The language network presented increased connectivity of inferior frontal and decreased connectivity within the right middle frontal and left inferior parietal cortices. The visuospatial network showed greater engagement of inferior parietal and frontal cortices. No effect of sex, nor age by sex interactions was observed. These findings provide evidence of strengthening of cortico-cortical and cortico-subcortical networks across childhood and adolescence.
The term cognitive reserve describes the capacity of the adult brain to minimise the clinical manifestation of a neurodegenerative process. The acquisition of cognitive reserve has been linked to the ...performance of certain intellectual and cognitive activities throughout the whole of the individual's life.
To create a new cognitive reserve questionnaire (CRQ), to establish its relation with the cognitive functions and to obtain the standard values in the cognitively healthy elderly Spanish population.
The sample consisted of 55 cognitively healthy controls and 53 patients with Alzheimer's disease. All the subjects were asked to complete the CRQ, which consists of eight items with several different possible answers, together with a brief neuropsychological battery.
Age had no significant influence on the score obtained on the CRQ in either of the groups, yet the number of years of schooling did exert a significant effect. In both groups significant correlations were found between the score on the CRQ and performance in neuropsychological tests that measure executive functioning.
The CRQ is a useful questionnaire for assessing the degree of cognitive reserve in healthy controls and in patients in the early stages of Alzheimer's disease. The CRQ is associated with the cognitive performance of executive functioning.
Cognitive reserve (CR) reflects the capacity of the brain to endure neuropathology in order to minimize clinical manifestations. Previous studies showed that CR modulates the patterns of brain ...activity in both healthy and clinical populations. In the present study we sought to determine whether reorganizations of functional brain resources linked to CR could already be observed in amnestic mild cognitive impairment (a-MCI) and mild Alzheimer's disease (AD) patients when performing a task corresponding to an unaffected cognitive domain. We further investigated if activity in regions showing task-induced deactivations, usually identified as pertaining to the default-mode network (DMN), was also influenced by CR.
Fifteen healthy elders, 15 a-MCI and 15 AD patients underwent functional magnetic resonance imaging (fMRI) during a speech comprehension task. Differences in the regression of slopes between CR proxies and blood-oxygen-level dependent (BOLD) signals across clinical groups were investigated for activation and deactivation areas. Correlations between significant fMRI results and a language comprehension test were also computed.
Among a-MCI and AD we observed positive correlations between CR measures and BOLD signals in task-induced activation areas directly processing speech, as well as greater deactivations in regions of the DMN. These relationships were inverted in healthy elders. We found no evidence that these results were mediated by gray matter volumes. Increased activity in left frontal areas and decreased activity in the anterior cingulate were related to better language comprehension in clinical evaluations.
The present findings provide evidence that the neurofunctional reorganizations related to CR among a-MCI and AD patients can be seen even when considering a preserved cognitive domain, being independent of gray matter atrophy. Areas showing both task-induced activations and deactivations are modulated by CR in an opposite manner when considering healthy elders versus patients. Brain reorganizations facilitated by CR may reflect behavioral compensatory mechanisms.
The objective was to study the association between cerebrospinal fluid (CSF) levels of amyloid-β (Aβ)(1-42), t-tau, and p-tau and cognitive performance along the Alzheimer's disease (AD) continuum ...from healthy subjects to AD patients and, specifically, among patients in the pre-dementia stage of the disease. A total of 101 subjects were studied: 19 healthy controls (CTR), 17 subjects with subjective memory complaints (SMC), 47 with mild cognitive impairment (MCI), and 18 AD patients. Only memory performance significantly correlated with CSF levels of Aβ(1-42), t-tau, and p-tau along the AD continuum. Subgroup analyses revealed that in SMC patients Aβ(1-42) levels positively correlated with the total recall score of the Free and Cued Selective Reminding Test (FCRST) (r = 0.666; p < 0.005), Digit Span (r = 0.752; p < 0.005), and CERAD world list learning (r = 0.697; p < 0.005). In MCI patients, a significant inverse correlation was found between the word list recall score from the CERAD and t-tau (r = -0.483; p < 0.005) and p-tau levels (r = -0.495; p < 0.005), as well as between the total recall subtest score from the FCRST and both t-tau (r = -0.420; p < 0.005) and p-tau levels (r = -0.422; p < 0.005). No significant correlations were found between other aspects of cognition and CSF levels in CTR or AD patients. These results indicate that memory performance is related to Aβ(1-42) levels in SMC, while it is associated with tau in the prodromal stage of the disease. This suggests that in the continuum from healthy aging to AD, memory performance is first related with Aβ(1-42) levels and then with t-tau or p-tau, before becoming independent of biomarker levels in the dementia stage.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Adults with psychotic disorders have abnormal connectivity of fronto-temporal networks. However, whether these abnormalities are present in adolescents with early psychosis has not been fully ...assessed. One-hundred and thirty-nine adolescents aged 12–18 underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging. Following motion correction, data were available for 44 participants with a psychosis risk syndrome, 34 patients with a first episode psychosis (FEP) and 35 healthy controls. Independent component analysis was performed to assess functional networks showing a fronto-temporal scope; this identified a language and a salience network. Mean fractional anisotropy was measured in clusters showing between-group differences in intrinsic functional connectivity (iFC). For the language network, there was a group effect within the right middle/inferior frontal gyrus, explained by reduced iFC in patients with an FEP relative to healthy controls, while in participants with a psychosis risk syndrome values of iFC were intermediate. In this region, values of iFC were positively correlated with mean fractional anisotropy in patients with an FEP. No group differences were observed in the salience network. Reduced iFC of the language network, in association with disrupted white matter microstructure, may characterize FEP during adolescence.
Cognitive reserve capacity may increase tolerance of neurodegenerative processes. However, its role regarding amyloid-β (Aβ42) deposition in cognitively normal subjects is not well understood. We ...aimed to investigate the association between areas showing Aβ42-related structural changes and cognitive reserve proxies in cognitively intact subjects showing normal or abnormal Aβ42 cerebrospinal fluid (CSF) concentrations. Thirty-three subjects (aged 55-85) underwent lumbar puncture and high resolution anatomical magnetic resonance imaging analyzed by voxel-based morphometry and cortical thickness procedures. Subjects with abnormal Aβ42 CSF levels showed significant left hippocampal atrophy and greater cortical thinning in parietal, temporal, and frontal regions (including the supramarginal and the anterior cingulate gyrus) compared to subjects with normal Aβ42 CSF levels. Using a multivariate general linear model, we investigated the relationship between these areas and cognitive reserve proxies. We found a significant relationship between decreased volume of the left hippocampus or decreased cortical thickness of the right supramarginal gyrus and higher cognitive reserve proxies only in the group with abnormal Aβ42 CSF levels. Thus, subjects with abnormal Aβ42 CSF levels (which may be at a higher risk of developing Alzheimer's disease) and with high scores on cognitive reserve proxies may be tolerating a more advanced neurodegenerative process in critical cortical and subcortical regions. The present results emphasize the relevance of evaluating cognitive reserve proxies, as well as the importance of using neuroimaging techniques for early diagnosis in individuals with higher reserve.
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