Coronary artery disease and its impact on the pulsatile brain: A functional NIRS study.

Recent studies have reported that optical indices of cerebral pulsatility are associated with cerebrovascular health in older adults. Such indices, including cerebral pulse amplitude and the pulse relaxation function (PRF), have been previously applied to quantify global and regional cerebral pulsatility. The aim of the present study was to determine whether these indices are modulated by cardiovascular status and whether they differ between individuals with low or high cardiovascular risk factors (LCVRF and HCVRF) and coronary artery disease (CAD). A total of 60 older adults aged 57-79 were enrolled in the study. Participants were grouped as LCVRF, HCVRF, and CAD. Participants were asked to walk freely on a gym track while a near-infrared spectroscopy (NIRS) device recorded hemodynamics data. Low-intensity, short-duration walking was used to test whether a brief cardiovascular challenge could increase the difference of pulsatility indices with respect to cardiovascular status. Results indicated that CAD individuals have higher global cerebral pulse amplitude compared with the other groups. Walking reduced global cerebral pulse amplitude and PRF in all groups but did not increase the difference across the groups. Instead, walking extended the spatial distribution of cerebral pulse amplitude to the anterior prefrontal cortex when CAD was compared to the CVRF groups. Further research is needed to determine whether cerebral pulse amplitude extracted from data acquired with NIRS, which is a noninvasive, inexpensive method, can provide an index to characterize the cerebrovascular status associated with CAD.

Preventing dementia by preventing stroke: The Berlin Manifesto.

The incidence of stroke and dementia are diverging across the world, rising for those in low- and middle-income countries and falling in those in high-income countries. This suggests that whatever factors cause these trends are potentially modifiable. At the population level, neurological disorders as a group account for the largest proportion of disability-adjusted life years globally (10%). Among neurological disorders, stroke (42%) and dementia (10%) dominate. Stroke and dementia confer risks for each other and share some of the same, largely modifiable, risk and protective factors. In principle, 90% of strokes and 35% of dementias have been estimated to be preventable. Because a stroke doubles the chance of developing dementia and stroke is more common than dementia, more than a third of dementias could be prevented by preventing stroke. Developments at the pathological, pathophysiological, and clinical level also point to new directions. Growing understanding of brain pathophysiology has unveiled the reciprocal interaction of cerebrovascular disease and neurodegeneration identifying new therapeutic targets to include protection of the endothelium, the blood-brain barrier, and other components of the neurovascular unit. In addition, targeting amyloid angiopathy aspects of inflammation and genetic manipulation hold new testable promise. In the meantime, accumulating evidence suggests that whole populations experiencing improved education, and lower vascular risk factor profiles (e.g., reduced prevalence of smoking) and vascular disease, including stroke, have better cognitive function and lower dementia rates. At the individual levels, trials have demonstrated that anticoagulation of atrial fibrillation can reduce the risk of dementia by 48% and that systolic blood pressure lower than 140 mmHg may be better for the brain. Based on these considerations, the World Stroke Organization has issued a proclamation, endorsed by all the major international organizations focused on global brain and cardiovascular health, calling for the joint prevention of stroke and dementia. This article summarizes the evidence for translation into action.

Executive functions profiles in traumatic brain injury adults: Implications for rehabilitation studies.

PRIMARY OBJECTIVE: This study aimed to identify and characterize profiles of executive functions (EF) following traumatic brain injury (TBI). RESEARCH DESIGN: The sample was comprised of 84 adult outpatients with mild and moderate/severe TBI who were assessed by means of a battery of EF tasks. A Hierarchical Cluster analysis was performed with tasks Z-scores. Clusters were compared by means of ANOVA and Chi-square analyses. MAIN OUTCOMES AND RESULTS: Three clusters were characterized by deficits in: (1) inhibition, flexibility and focused attention; (2) inhibition, flexibility, working memory and focused attention; and (3) no expressive executive deficits. Clusters did not differ in clinical or demographical variables. CONCLUSIONS: The first cluster replicated findings of previous studies on TBI EF profiles. IT is suggested that TBI rehabilitation studies of EF must select participants by their EF profile rather than for clinical or demographical variables.

False memories to emotional stimuli are not equally affected in right- and left-brain-damaged stroke patients.

Previous research has attributed to the right hemisphere (RH) a key role in eliciting false memories to visual emotional stimuli. These results have been explained in terms of two right-hemisphere properties: (i) that emotional stimuli are preferentially processed in the RH and (ii) that visual stimuli are represented more coarsely in the RH. According to this account, false emotional memories are preferentially produced in the RH because emotional stimuli are both more strongly and more diffusely activated during encoding, leaving a memory trace that can be erroneously reactivated by similar but unstudied emotional items at test. If this right-hemisphere hypothesis is correct, then RH damage should result in a reduction in false memories to emotional stimuli relative to left-hemisphere lesions. To investigate this possibility, groups of right-brain-damaged (RBD, N=15), left-brain-damaged (LBD, N=15) and healthy (HC, N=30) participants took part in a recognition memory experiment with emotional (negative and positive) and non-emotional pictures. False memories were operationalized as incorrect responses to unstudied pictures that were similar to studied ones. Both RBD and LBD participants showed similar reductions in false memories for negative pictures relative to controls. For positive pictures, however, false memories were reduced only in RBD patients. The results provide only partial support for the right-hemisphere hypothesis and suggest that inter-hemispheric cooperation models may be necessary to fully account for false emotional memories.

Registered report: Age-preserved semantic memory and the CRUNCH effect manifested as differential semantic control networks: An fMRI study.

Semantic memory representations are generally well maintained in aging, whereas semantic control is thought to be more affected. To explain this phenomenon, this study tested the predictions of the Compensation-Related Utilization of Neural Circuits Hypothesis (CRUNCH), focusing on task demands in aging as a possible framework. The CRUNCH effect would manifest itself in semantic tasks through a compensatory increase in neural activation in semantic control network regions but only up to a certain threshold of task demands. This study compares 39 younger (20-35 years old) with 39 older participants (60-75 years old) in a triad-based semantic judgment task performed in an fMRI scanner while manipulating task demand levels (low versus high) through semantic distance. In line with the CRUNCH predictions, differences in neurofunctional activation and behavioral performance (accuracy and response times) were expected in younger versus older participants in the low- versus high-demand conditions, which should be manifested in semantic control Regions of Interest (ROIs). Our older participants had intact behavioral performance, as proposed in the literature for semantic memory tasks (maintained accuracy and slower response times (RTs)). Age-invariant behavioral performance in the older group compared to the younger one is necessary to test the CRUNCH predictions. The older adults were also characterized by high cognitive reserve, as our neuropsychological tests showed. Our behavioral results confirmed that our task successfully manipulated task demands: error rates, RTs and perceived difficulty increased with increasing task demands in both age groups. We did not find an interaction between age group and task demand, or a statistically significant difference in activation between the low- and high-demand conditions for either RTs or accuracy. As for brain activation, we did not find the expected age group by task demand interaction, or a significant main effect of task demand. Overall, our results are compatible with some neural activation in the semantic network and the semantic control network, largely in frontotemporoparietal regions. ROI analyses demonstrated significant effects (but no interactions) of task demand in the left and right inferior frontal gyrus, the left posterior middle temporal gyrus, the posterior inferior temporal gyrus and the prefrontal gyrus. Overall, our test did not confirm the CRUNCH predictions.

The adaptive aging brain: evidence from the preservation of communication abilities with age.

Neurofunctional reorganization with age is suspected to occur for many cognitive components including communication abilities. Several functional neuroimaging studies of elderly individuals have reported the occurrence of an interhemispheric neurofunctional reorganization characterized by more bilateral activation patterns. Other studies have indicated that the preservation of some other cognitive abilities is associated with some intrahemispheric reorganization following either a posterior-anterior or an anterior-posterior shift in aging. Interestingly, other studies have shown that age-related neurofunctional reorganization is task-load-dependent. Taken together, these studies suggest that neurofunctional reorganization in aging is based on a more dynamic, flexible and adaptive neurofunctional process than previously proposed. This review summarizes the different factors that are thought to support the preservation of the semantic processing of words in aging, and highlights a multidetermined and complex set of processes such as the nature of the specific cognitive processes, task complexity and cognitive strategy, characterizing the neurofunctional reorganization in aging that allows for optimal cognitive abilities. In so doing, it provides the background for future study looking at the neurofunctional dimensions of the impact of neurodegenerative diseases on cognitive abilities.

The role of the left anterior temporal lobe in exception word reading: reconciling patient and neuroimaging findings.

Semantic dementia (SD) is a neurodegenerative disease that occurs following the atrophy of the anterior temporal lobes (ATLs). It is characterised by the degradation of semantic knowledge and difficulties in reading exception words (surface dyslexia). This disease has highlighted the role of the ATLs in the process of exception word reading. However, imaging studies in healthy subjects have failed to detect activation of the ATLs during exception word reading. The aim of the present study was to test whether the functional brain regions that mediate exception word reading in normal readers overlap those brain regions atrophied in SD. In Study One, we map the brain regions of grey matter atrophy in AF, a patient with mild SD and surface dyslexia profile. In Study Two, we map the activation pattern associated with exception word compared to pseudoword reading in young, healthy participants using fMRI. The results revealed areas of significant activation in healthy subjects engaged in the exception word reading task in the left anterior middle temporal gyrus, in a region observed to be atrophic in the patient AF. These results reconcile neuropsychological and functional imaging data, revealing the critical role of the left ATL in exception word reading.

Fronto-striatal contribution to lexical set-shifting.

Fronto-striatal circuits in set-shifting have been examined in neuroimaging studies using the Wisconsin Card Sorting Task (WCST) that requires changing the classification rule for cards containing visual stimuli that differ in color, shape, and number. The present study examined whether this fronto-striatal contribution to the planning and execution of set-shifts is similar in a modified sorting task in which lexical rules are applied to word stimuli. Young healthy adults were scanned with functional magnetic resonance imaging while performing the newly developed lexical version of the WCST: the Wisconsin Word Sorting Task. Significant activation was found in a cortico-striatal loop that includes area 47/12 of the ventrolateral prefrontal cortex (PFC), and the caudate nucleus during the planning of a set-shift, and in another that includes the posterior PFC and the putamen during the execution of a set-shift. However, in the present lexical task, additional activation peaks were observed in area 45 of the ventrolateral PFC area during both matching periods. These results provide evidence that the functional contributions of the various fronto-striatal loops are not dependent on the modality of the information to be manipulated but rather on the specific executive processes required.

Communicative clusters after a right-hemisphere stroke: are there universal clinical profiles?.

OBJECTIVE: The current research aimed at classifying communication profiles among right-brain-damaged adults with an intercultural perspective, and so begins to fill in a long-standing gap in the literature. METHOD: The sample was made up of 112 right-brain-damaged individuals from three nationalities (Canadians, Brazilians and Argentineans). They were assessed using 13 language tasks from the Protocol MEC in Spanish, Brazilian Portuguese and French. RESULTS: A hierarchical cluster analysis led to four distinct clinical profiles of communication. Since only a few distinctions between nationalities were observed, the results suggest that there probably is a partial universality of clinical profiles of communication impairments after a right brain damage. CONCLUSIONS: This study proposes a preliminary taxonomy of communication disorders among right-brain-damaged individuals with cross-cultural implications. The exploration of associated stroke sites and neuropsychological concomitant deficits would contribute to the eventual development of a more accurate clinical intervention.

Exploring attention in the bilingualism continuum: A resting-state functional connectivity study.

This study explores the effects of bilingualism on the subcomponents of attention using resting state functional connectivity analysis (rsFC). Unlike previous studies, measures of bilingualism - L2 Age of Acquisition (AOA), L2 exposure, and L2 proficiency - were examined along a continuum to study attentional mechanisms using rsFC instead of dichotomizing them. 20 seed regions were pre-selected for the three subcomponents of attention. The results showed a positive association between behavioral performance and rsFC for the seeds in alerting and orienting network; this was not true for the seeds in the executive control network. Secondly, rsFC for attention networks varied with different levels of bilingualism. The objective measures of bilingualism modulate all three attention networks. While the subjective measures such as L2 AOA modulates specific attention network. Thus, language performance in contrast to self-reported information, as a measure of bilingualism, has a greater potential to tap into the role of bilingualism in attentional processes.

Multifactorial approaches to study bilingualism in the aging population: Past, present, future.

A better understanding and more reliable classification of bilinguals has been progressively achieved through the fine-tuning methodology and simultaneously optimizing the measurement tools. However, the current understanding is far from generalization to a larger population varying in different measures of bilingualism-L2 Age of acquisition (L2 AOA), L2 usage and exposure, and L2 proficiency. More recent studies have highlighted the importance of modeling bilingualism as a continuous variable. An in-depth look at the role of bilingualism, comparing groups, may be considered a reductionist approach, i.e., grouping based on one measure of bilingualism (e.g., L2 AOA) may not account for variability in other measures of bilingualism (L2 exposure, L2 use or L2 proficiency, amongst others) within and between groups. Similarly, a multifactorial dimension is associated with cognitive performance, where not all domains of cognition and subcomponents are equally influenced by bilingualism. In addition, socio-cultural and demographical factors may add another dimension to the impact of bilingualism on cognitive performance, especially in older adults. Nevertheless, not many studies have controlled or used the multiple socio-cultural and demographical factors as a covariate to understand the role of different aspects of bilingualism that may influence cognitive performance differently. Such an approach would fail to generalize the research findings to a larger group of bilinguals. In the present review paper, we illustrate that considering a multifactorial approach to different dimensions of bilingual study may lead to a better understanding of the role of bilingualism on cognitive performance. With the evolution of various fine-tuned methodological approaches, there is a greater need to study variability in bilingual profiles that can help generalize the result universally.

Age, multimorbidity and dementia with health care costs in older people in Alberta: a population-based retrospective cohort study.

BACKGROUND: The growing burden associated with population aging, dementia and multimorbidity poses potential challenges for the sustainability of health systems worldwide. We sought to examine how the intersection among age, dementia and greater multimorbidity is associated with health care costs. METHODS: We did a retrospective population-based cohort study in Alberta, Canada, with adults aged 65 years and older between April 2003 and March 2017. We identified 31 morbidities using algorithms (30 algorithms were validated), which were applied to administrative health data, and assessed costs associated with hospital admission, provider billing, ambulatory care, medications and long-term care (LTC). Actual costs were used for provider billing and medications; estimated costs for inpatient and ambulatory patients were based on the Canadian Institute for Health Information's resource intensive weights and Alberta's cost of a standard hospital stay. Costs for LTC were based on an estimated average daily cost. RESULTS: There were 827 947 people in the cohort. Dementia was associated with higher mean annual total costs and individual mean component costs for almost all age categories and number of comorbidities categories (differences in total costs ranged from $27 598 to $54 171). Similarly, increasing number of morbidities was associated with higher mean total costs and component costs (differences in total costs ranged from $4597 to $10 655 per morbidity). Increasing age was associated with higher total costs for people with and without dementia, driven by increasing LTC costs (differences in LTC costs ranged from $115 to $9304 per age category). However, there were no consistent trends between age and non-LTC costs among people with dementia. When costs attributable to LTC were excluded, older age tended to be associated with lower costs among people with dementia (differences in non-LTC costs ranged from -$857 to -$7365 per age category). INTERPRETATION: Multimorbidity, older age and dementia were all associated with increased use of LTC and thus health care costs, but some costs among people with dementia decreased at older ages. These findings illustrate the complexity of projecting the economic consequences of the aging population, which must account for the interplay between multimorbidity and dementia.

Functional network and structural connections involved in picture naming.

We mapped the left hemisphere cortical regions and fiber bundles involved in picture naming in adults by integrating task-based fMRI with dMRI tractography. We showed that a ventral pathway that "maps image and sound to meaning" involves the middle occipital, inferior temporal, superior temporal, inferior frontal gyri, and the temporal pole where a signal exchange is made possible by the inferior fronto-occipital, inferior longitudinal, middle longitudinal, uncinate fasciculi, and the extreme capsule. A dorsal pathway that "maps sound to speech" implicates the inferior temporal, superior temporal, inferior frontal, precentral gyri, and the supplementary motor area where the arcuate fasciculus and the frontal aslant ensure intercommunication. This study provides a neurocognitive model of picture naming and supports the hypothesis that the ventral indirect route passes through the temporal pole. This further supports the idea that the inferior and superior temporal gyri may play pivotal roles within the dual-stream framework of language.

Processing the emotions in words: the complementary contributions of the left and right hemispheres.

A dual-process model is suggested for the processing of words with emotional meaning in the cerebral hemispheres. While the right hemisphere and valence hypotheses have long been used to explain the results of research on emotional stimulus processing, including nonverbal and verbal stimuli, data on emotional word processing are mostly inconsistent with both hypotheses. Three complementary lines of research data from behavioral, electrophysiological, and neuroimaging studies seem to suggest that both hemispheres have access to the meanings of emotional words, although their time course of activation may be different. The left hemisphere activates these words automatically early in processing, whereas the right hemisphere gains access to emotional words slowly when attention is recruited by the meaning of these words in a controlled manner. This processing dichotomy probably corroborates the complementary roles the two hemispheres play in data processing.

Age-preserved semantic memory and the CRUNCH effect manifested as differential semantic control networks: An fMRI study.

Semantic memory representations are overall well-maintained in aging whereas semantic control is thought to be more affected. To explain this phenomenon, this study aims to test the predictions of the Compensation Related Utilization of Neural Circuits Hypothesis (CRUNCH) focusing on task demands in aging as a possible framework. The CRUNCH effect would manifest itself in semantic tasks through a compensatory increase in neural activation in semantic control network regions but only up to a certain threshold of task demands. This study will compare 40 young (20-35 years old) with 40 older participants (60-75 years old) in a triad-based semantic judgment task performed in an fMRI scanner while manipulating levels of task demands (low vs. high) through semantic distance. In line with the CRUNCH predictions, differences in neurofunctional activation and behavioral performance (accuracy and response times) are expected in young vs. old participants in the low- vs. high-demand conditions manifested in semantic control Regions of Interest.

Cortical thinning is associated with brain pulsatility in older adults: An MRI and NIRS study.

Aging is accompanied by global brain atrophy occurring unequally across the brain. Cortical thinning is seen with aging with a larger loss in the frontal and temporal subregions. We explored the link between regional cortical thickness and regional cerebral pulsatility. Sixty healthy individuals were divided into two age groups, young (aged 19-31) and older (aged 65-75) adults. Each participant underwent a near-infrared spectroscopy (NIRS) scan to index regional brain pulsatility from cerebral pulse-transit-time-to-the peak-of-the-pulse (PTTp), an anatomical magnetic resonance imaging (MRI) and a phase-contrast MRI (PC-MRI) scan to measure arterial and cerebrospinal fluid (CSF) pulsatility. In older adults, the greatest association between cerebral pulsatility and cortical thickness was found in superior and middle temporal and superior, middle and inferior frontal areas, which are the regions perfused first by the internal carotid arteries. This association dropped in the postcentral and superior parietal regions. These findings suggest higher brain pulsatility as a potential risk factor contributing to cortical thinning for some brain regions more than others.

Reducing the Risk of Cognitive Decline and Dementia: WHO Recommendations.

With population ageing worldwide, dementia poses one of the greatest global challenges for health and social care in the 21st century. In 2019, around 55 million people were affected by dementia, with the majority living in low- and middle-income countries. Dementia leads to increased costs for governments, communities, families and individuals. Dementia is overwhelming for the family and caregivers of the person with dementia, who are the cornerstone of care and support systems throughout the world. To assist countries in addressing the global burden of dementia, the World Health Organisation (WHO) developed the Global Action Plan on the Public Health Response to Dementia 2017-2025. It proposes actions to be taken by governments, civil society, and other global and regional partners across seven action areas, one of which is dementia risk reduction. This paper is based on WHO Guidelines on risk reduction of cognitive decline and dementia and presents recommendations on evidence-based, multisectoral interventions for reducing dementia risks, considerations for their implementation and policy actions. These global evidence-informed recommendations were developed by WHO, following a rigorous guideline development methodology and involved a panel of academicians and clinicians with multidisciplinary expertise and representing geographical diversity. The recommendations are considered under three broad headings: lifestyle and behaviour interventions, interventions for physical health conditions and specific interventions. By supporting health and social care professionals, particularly by improving their capacity to provide gender and culturally appropriate interventions to the general population, the risk of developing dementia can be potentially reduced, or its progression delayed.

Functional Connectivity of Successful Picture-Naming: Age-Specific Organization and the Effect of Engaging in Stimulating Activities.

Aging is a lifelong process that starts at birth. Throughout the course of their life, individuals are exposed to various levels of stimulating activities. A higher level of engagement in such activities is suspected to protect against the normal course of cognitive aging or the cognitive manifestations of age-related brain diseases. However, the exact mechanism underlying such protective action remains unclear. The concept of the neurocognitive reserve was introduced to refer to the hypothesis that engagement in stimulating activities shapes brain structure and function, thus indirectly allowing for better preserved cognitive abilities. Although it is known that word production is among the best-preserved cognitive abilities in aging, the underlying neurofunctional mechanisms that allow this relative preservation are still unknown, and it is still unclear how engagement in stimulating activities affects these processes. The objective of this study is to describe the brain functional connectivity patterns associated with picture-naming abilities in younger and older adults with varying levels of engagement in stimulating activities, as a proxy for neurocognitive reserve. A mediation analysis was applied to determine whether the association between reserve proxies and naming accuracy is dependent on task FC. Results show that naming accuracy depends on the posterior cingulate cortex (PCC) functional decoupling in both younger and older adults but through different pathways. While high-performing older adults rely on the asynchronization of this area from motor speech regions' activity, the best-performing younger adults rely on the functional decoupling with language-related regions. Mediation analysis reveals that the PCC decoupling mediates the relationship between the level of engagement in stimulating activities and naming accuracy in younger adults, but not in older adults. These findings suggest that reserve-related mechanisms may be more critical for naming in early adult life, while older adults' neurofunctional organization may benefit more from a lifetime of acquired knowledge.

Association of Age With Risk of Kidney Failure in Adults With Stage IV Chronic Kidney Disease in Canada.

Importance: With population aging, the burden of many age-related chronic conditions, including kidney failure, is increasing globally. Objective: To investigate the risks of kidney failure and death in adults with incident stage IV chronic kidney disease (CKD). Design, Setting, and Participants: This population-based cohort study obtained data recorded between July 30, 2002, and March 31, 2014, from the linked laboratory and administrative data set of Alberta Health in Alberta, Canada. All adults of the province of Alberta with stage IV CKD (estimated glomerular filtration rate [eGFR] of 15-30 mL/min/1.73 m2) were eligible for inclusion. Included individuals were followed up from study entry until the date of kidney failure, death, or censoring, whichever occurred first. Observations were censored at the date of emigration from the province, the study end date (March 31, 2017), or at 10 years after study entry. Data analyses were performed from January 2020 to June 2020. Main Outcomes and Measures: The primary outcome was kidney failure, defined as the earlier of either renal replacement (dialysis or kidney transplant) initiation or severe kidney impairment (eGFR <10 mL/min/1.73 m2). Incidence of stage IV CKD in Alberta was examined over time, along with the association between age at study entry and the competing risks of kidney failure and death. Cumulative incidence functions (95% CIs) were estimated to summarize absolute risks over time across categories of age, accounting for sex, diabetes, cardiovascular disease, eGFR, and albuminuria. Results: The study included 30 801 adults (mean [SD] age, 76.8 [13.3] years; 17 294 women [56.1%]) with stage IV CKD. Of these, 5511 developed kidney failure (17.9%) and 16 285 died (52.9%). The incidence rate of stage IV CKD increased sharply with advancing age; the absolute risk of kidney failure decreased with advancing age, and the risk of death increased, especially in those aged 85 years or older. Compared with the 5-year risk of death, the 5-year risk of kidney failure was higher in people younger than 65 years, similar in people aged 65 to 74 years, and lower for older age groups. For those aged 75 years or older, the risk of death was much higher than the risk of kidney failure: 6-fold higher among those aged 75 to 84 years (0.51 [95% CI, 0.5-0.52] vs 0.09 [95% CI, 0.08-0.09]) and 25-fold higher among those aged 85 years or older (0.75 [95% CI, 0.74-0.76] vs 0.03 [95% CI, 0.02-0.03]). The risk of death was higher than the risk of kidney failure by 24-fold among those aged 85 to 94 years (0.73 [95% CI, 0.72-0.74] vs 0.03 [95% CI, 0.02-0.03]) and by 149-fold among those aged 95 years or older (0.89 [95% CI, 0.87-0.92] vs <0.01 [95% CI, <0.01 to 0.01]). Conclusions and Relevance: This study found that, although the incidence rate of stage IV CKD increased with advancing age, the absolute risk of kidney failure decreased. Unlike other age-related conditions, the expected increase in the burden of kidney failure in the older adults may be less dramatic than expected.