Several concepts, which in the aggregate get might be used to account for “resilience” against age- and disease-related changes, have been the subject of much research. These include brain reserve, ...cognitive reserve, and brain maintenance. However, different investigators have use these terms in different ways, and there has never been an attempt to arrive at consensus on the definition of these concepts. Furthermore, there has been confusion regarding the measurement of these constructs and the appropriate ways to apply them to research. Therefore the reserve, resilience, and protective factors professional interest area, established under the auspices of the Alzheimer's Association, established a whitepaper workgroup to develop consensus definitions for cognitive reserve, brain reserve, and brain maintenance. The workgroup also evaluated measures that have been used to implement these concepts in research settings and developed guidelines for research that explores or utilizes these concepts. The workgroup hopes that this whitepaper will form a reference point for researchers in this area and facilitate research by supplying a common language.
Subjects with mild cognitive impairment are at risk of developing Alzheimer's disease. Cognitive stimulation is an emerging intervention in the field of neurology and allied sciences, having already ...been shown to improve cognition in subjects with mild cognitive impairment. Yet no studies have attempted to unravel the brain mechanisms that support such improvement. This study uses functional magnetic resonance imaging to measure the effect of memory training on brain activation in older adults with mild cognitive impairment and to assess whether it can reverse the brain changes associated with mild cognitive impairment. Brain activation associated with verbal encoding and retrieval was recorded twice prior to training and once after training. In subjects with mild cognitive impairment, increased activation was found after training within a large network that included the frontal, temporal and parietal areas. Healthy controls showed mostly areas of decreased activation following training. Comparison with pre-training indicated that subjects with mild cognitive impairment used a combination of specialized areas; that is, areas activated prior to training and new alternative areas activated following training. However, only activation of the right inferior parietal lobule, a new area of activation, correlated with performance. Furthermore, the differences between the brain activation patterns of subjects with mild cognitive impairment and those of healthy controls were attenuated by training in a number of brain regions. These results indicate that memory training can result in significant neural changes that are measurable with brain imaging. They also show that the brains of people with mild cognitive impairment remain highly plastic.
Background Alzheimer's disease is a neurodegenerative disease with progressive cognitive impairments that are likely to affect the compensatory mechanisms and the cerebral activation patterns of the ...patients. Methods Functional neuroimaging was used to test the effect of disease severity on the brain activation of persons at risk for Alzheimer's disease and to highlight the process of compensation in some of these individuals. This was done for the verbal learning of either semantically related or semantically unrelated word pairs. Twenty-six persons with mild cognitive impairment (MCI) were separated into two groups, MCI higher-cognition and MCI lower-cognition, with a split-median on their scores for the Mattis Dementia Rating Scale. A group of 14 healthy older adults were matched to the MCI participants. Results In both task conditions, MCI higher-cognition activated additional regions, relative to control subjects, in the right ventrolateral and dorsolateral prefrontal brain areas. Additional areas of hyperactivation were found in the right prefrontal area 45 when encoding semantically related word pairs and in the left hippocampus during encoding of unrelated word pairs. In contrast, MCI lower-cognition failed to show additional prefrontal activations when compared with healthy control subjects and showed decreased activation in posterior areas. Conclusions These results are in line with compensation occurring at the beginning of the MCI continuum and with the breakdown of compensation in patients experiencing more severe symptoms.
Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer’s disease that is characterized by impairments in episodic memory. Recent evidence has shown that inhibitory control is ...also impaired in aMCI. The aim of the present meta-analysis was to quantify inhibitory control ability in individuals with aMCI by examining performance across a range of well-defined inhibition paradigms that tapped into one of three inhibitory control subtypes (i) interference control (e.g., Stroop task), (ii) response inhibition (e.g., Go/Nogo task), or (iii) inhibition of cognitive sets (Wisconsin Card Sort Task). Reference databases (PsychINFO, PubMed, and Web of Science) were searched for studies comparing individuals with aMCI to healthy controls on behavioural measures of inhibition. Across 70 effect sizes involving 2184 adults with aMCI and 3049 controls, overall inhibition deficits of moderate magnitude (
g
= −0.73) were found among individuals with aMCI. Inhibition deficits were moderate in size regardless of inhibitory control subtype: interference control (
g
= −0.74), response inhibition (
g
= −0.71), inhibition of cognitive sets (
g
= −0.76). Subgroup analyses revealed that Stroop outcome measure (reaction time vs. accuracy) and recruitment source (clinical vs. community) moderated interference control deficits. Together these findings support a generalized inhibition deficit in aMCI, and suggest that inhibition tasks should be included routinely in neuropsychological test batteries to provide a more comprehensive overview of executive dysfunction in aMCI.
The goal of this study was to assess inhibition and goal maintenance in persons with Alzheimer's disease, mild cognitive impairment, healthy older adults and younger adults. This was done by using a ...task that compared the Stroop effect in pure blocks, that comprised only incongruent trials, with the Stroop effect in mixed blocks, in which 25% of trials were incongruent and 75% were congruent (Kane & Engle, 2003). Those conditions were administered to 20 healthy younger and 20 older control participants, and to 20 participants meeting criteria for MCI and 11 for AD. Results show reduced resistance to interference as a consequence of healthy aging and only partially impaired goal-maintenance capacities. Interference and goal maintenance are also impaired when comparing MCI and AD to healthy older adults, with AD suffering from a more severe impairment than MCI. In addition, there is a partial preservation of goal-maintenance capacities in MCI because reducing response speed allows them to maintain a level of error rate similar to that of healthy older adults. In contrast, AD persons suffer from a complete breakdown of goal-maintenance capacities, as is suggested by deficits on both response time and error rates.
Our goal was to test the effect of disease severity on the brain activation associated with two executive processes: manipulation and divided attention.
This was achieved by administrating a ...manipulation task and a divided attention task using functional magnetic resonance imaging to 24 individuals with mild cognitive impairment (MCI) and 14 healthy controls matched for age, sex and education. The Mattis Dementia Rating Scale was used to divide persons with MCI into those with better and worse cognitive performances.
Both tasks were associated with more brain activation in the MCI group with higher cognition than in healthy controls, particularly in the left frontal areas. Correlational analyses indicated that greater activation in a frontostriatal network hyperactivated by the higher-cognition group was related with better task performance, suggesting that these activations may support functional reorganization of a compensatory nature. By contrast, the lower-cognition group failed to show greater cerebral hyperactivation than controls during the divided attention task and, during the manipulation task, and showed less brain activation than controls in the left ventrolateral cortex, a region commonly hypoactivated in patients with Alzheimer’s disease.
These findings indicate that, during the early phase of MCI, executive functioning benefits from neural reorganization, but that a breakdown of this brain plasticity characterizes the late stages of MCI.
Brain maintenance refers to the fact that some older adults experience few age-related changes in the brain, which helps maintain their cognition. The goal of this study was to assess maintenance of ...white matter integrity by testing whether reserve proxies, measuring factors associated to a stimulating lifestyle, affect the maintenance of white matter integrity. Another goal was to measure whether maintenance of white matter integrity explains inter-individual differences in working memory (WM). Forty-one cognitively healthy older adults received a structural magnetic resonance imaging (MRI) examination to measure white matter lesions. They completed an n-back WM task with different loads (1- & 2-back), along with a questionnaire on their lifestyle. There was a positive association between age and volume of white matter lesions. This association was no longer found in those with higher scores on reserve proxies. In addition
,
smaller volumes of white matter lesions were associated with better performance than expected for age in the 1-back WM task. Better WM is associated with the maintenance of white matter integrity in older adults, which in turn is linked to measures reflecting a stimulating lifestyle throughout life.
Objective: This study examines working memory (WM) in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Method: Performances on sentence span and operation span were measured in ...individuals meeting criteria for MCI (n = 20) and AD (n = 16) as well as in healthy older adults (n = 20). In addition, the effect of retention interval was assessed by manipulating the length of first and last items of trials (long-short vs. short-long), as forgetting might contribute to impaired performance in AD and MCI. Results: Results show a group effect (p < .001, η2 = .47): In both conditions and for both material types, WM span is lower in AD than in MCI (p < .001), which in turn is lower than in healthy aging (p < .05). An effect of retention interval on complex span was found for all groups (p < .001, η2 = .57), supporting a role for forgetting within WM. When computing a proportional interval effect (p < .05, η2 = .12), it was found that persons with AD were more sensitive to retention interval than were healthy older adults (p < .05). Among persons with MCI, those who later showed significant clinical deterioration or progression to AD were more affected by retention interval (p < .05, η2 = .28) than were those who remained stable. Furthermore, deficits in AD are associated with a higher proportion of intrusion errors, particularly those from the current trial (p < .05, η2 = .15), which could reflect inhibitory processes. Conclusions: Overall, these results indicate impaired WM in age-related disorders with a gradient between MCI and AD. Retention interval increases deficit in persons with AD. It also shows potential in predicting a negative prognosis in those with MCI.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ
Maintaining grey matter within the hippocampus is important for healthy cognition. Playing 3D-platform video games has previously been shown to promote grey matter in the hippocampus in younger ...adults. In the current study, we tested the impact of 3D-platform video game training (i.e., Super Mario 64) on grey matter in the hippocampus, cerebellum, and the dorsolateral prefrontal cortex (DLPFC) of older adults. Older adults who were 55 to 75 years of age were randomized into three groups. The video game experimental group (VID; n = 8) engaged in a 3D-platform video game training over a period of 6 months. Additionally, an active control group took a series of self-directed, computerized music (piano) lessons (MUS; n = 12), while a no-contact control group did not engage in any intervention (CON; n = 13). After training, a within-subject increase in grey matter within the hippocampus was significant only in the VID training group, replicating results observed in younger adults. Active control MUS training did, however, lead to a within-subject increase in the DLPFC, while both the VID and MUS training produced growth in the cerebellum. In contrast, the CON group displayed significant grey matter loss in the hippocampus, cerebellum and the DLPFC.
Hyperactivation, which is defined as a higher level of activation in patients compared to cognitively unimpaired older adults (controls; CTL), might represent an early signature of Alzheimer's ...Disease (AD). The goal of this study was to assess the presence and location of hyperactivation in individuals with mild cognitive impairment (MCI) who were later diagnosed with dementia, examine how hyperactivation changes longitudinally, and whether it is related to time before dementia. Forty participants, 26 with MCI and 14 CTL were enrolled in the study. Magnetic resonance imaging was used to measure functional activation while participants encoded word-pairs as well as cortical thickness and regional brain volume at study entry (Y0) and two years later (Y2). Clinical follow-up was completed every two years following study entry to identify progressors (pMCI), that is, individuals who later received a diagnosis of dementia. Task-related activation was assessed in pMCI in both hippocampi and in regions showing greater cortical thinning from Y0 to Y2 compared to CTLs. Hyperactivation was found in pMCI individuals in the right supramarginal gyrus. Persons with pMCI also showed hypoactivation in the left hippocampus and left pars opercularis. Both hyper- and hypoactivation were present at Y0 and Y2 and did not change longitudinally. Activation was not associated with time before dementia diagnosis. Smaller volume and thinner cortical thickness were associated with shorter time to diagnosis in the left hippocampus and left pars opercularis. In conclusion, hyperactivation was found in individuals who later progressed to dementia, confirming that it might represent an early biomarker to identify individuals in the prodromal phase of AD and that its understanding could contribute to elucidate the key brain mechanisms that precede dementia.
•Hyperactivation of the right parietal region was found in MCI progressors.•Hypoactivation was found in the hippocampal and frontal regions.•This overall pattern was specific to MCI who progressed to dementia.