572 research outputs found
Improved Cardiorespiratory Fitness Is Associated with Increased Cortical Thickness in Mild Cognitive Impairment
Cortical atrophy is a biomarker of Alzheimer’s disease (AD) that correlates with clinical symptoms. This study examined changes in cortical thickness from before to after an exercise intervention in mild cognitive impairment (MCI) and healthy elders. Thirty physically inactive older adults (14 MCI, 16 healthy controls) underwent MRI before and after participating in a 12-week moderate intensity walking intervention. Participants were between the ages of 61 and 88. Change in cardiorespiratory fitness was assessed using residualized scores of the peak rate of oxygen consumption (V̇O2peak) from pre- to post-intervention. Structural magnetic resonance images were processed using FreeSurfer v5.1.0. V̇O2peak increased an average of 8.49%, which was comparable between MCI and healthy elders. Overall, cortical thickness was stable except for a significant decrease in the right fusiform gyrus in both groups. However, improvement in cardiorespiratory fitness due to the intervention (V̇O2peak) was positively correlated with cortical thickness change in the bilateral insula, precentral gyri, precuneus, posterior cingulate, and inferior and superior frontal cortices. Moreover, MCI participants exhibited stronger positive correlations compared to healthy elders in the left insula and superior temporal gyrus. A 12-week moderate intensity walking intervention led to significantly improved fitness in both MCI and healthy elders. Improved V̇O2peak was associated with widespread increased cortical thickness, which was similar between MCI and healthy elders. Thus, regular exercise may be an especially beneficial intervention to counteract cortical atrophy in all risk groups, and may provide protection against future cognitive decline in both healthy elders and MCI
Exercise Training and Functional Connectivity Changes in Mild Cognitive Empairment and Healthy Elders
Background: Effective interventions are needed to improve brain function in mild cognitive impairment (MCI), an early stage of Alzheimer’s disease (AD). The posterior cingulate cortex (PCC)/precuneus is a hub of the default mode network (DMN) and is preferentially vulnerable to disruption of functional connectivity in MCI and AD. Objective: We investigated whether 12 weeks of aerobic exercise could enhance functional connectivity of the PCC/precuneus in MCI and healthy elders. Methods: Sixteen MCI and 16 healthy elders (age range = 60–88) engaged in a supervised 12-week walking exercise intervention. Functional MRI was acquired at rest; the PCC/precuneus was used as a seed for correlated brain activity maps. Results: A linear mixed effects model revealed a significant interaction in the right parietal lobe: the MCI group showed increased connectivity while the healthy elders showed decreased connectivity. In addition, both groups showed increased connectivity with the left postcentral gyrus. Comparing pre to post intervention changes within each group, the MCI group showed increased connectivity in 10 regions spanning frontal, parietal, temporal and insular lobes, and the cerebellum. Healthy elders did not demonstrate any significant connectivity changes. Conclusion: The observed results show increased functional connectivity of the PCC/precuneus in individuals with MCI after 12 weeks of moderate intensity walking exercise training. The protective effects of exercise training on cognition may be realized through the enhancement of neural recruitment mechanisms, which may possibly increase cognitive reserve. Whether these effects of exercise training may delay further cognitive decline in patients diagnosed with MCI remains to be demonstrated
Subjective Well-Being and Bilateral Anterior Insula Functional Connectivity After Exercise Intervention in Older Adults With Mild Cognitive Impairment
While it is well known that exercise training is associated with improvement in subjective well-being among older adults, it is unclear if individuals with cognitive impairment experience the same effects elicited by exercise on subjective well-being. We further explored whether the bilateral anterior insula network may be an underlying neural mechanism for the exercise training-related improvements in subjective well-being. We investigated the effects of exercise training on subjective well-being in older adults (78.4 ± 7.1 years) with mild cognitive impairment (MCI; n = 14) and a cognitively normal (CN; n = 14) control group. We specifically assessed the relationship between changes in subjective well-being and changes in functional connectivity (FC) with the bilateral anterior insula from before to after exercise training. Cardiorespiratory fitness, subjective well-being, and resting-state fMRI were measured before and after a 12-week moderate-intensity walking intervention. A seed-based correlation analysis was conducted using the bilateral anterior insula as a priori seed regions of interest. The associations between bilateral anterior insula FC with other brain regions and subjective well-being were computed before and after exercise training, respectively, and the statistical difference between the correlations (before vs after exercise training) was evaluated. There was a significant Group (MCI vs CN) × Time (before vs after exercise training) interaction for subjective well-being, such that while those with MCI demonstrated significantly increased subjective well-being after exercise training, no changes in subjective well-being were observed in CN. Participants with MCI also showed an exercise training-related increase in the bilateral anterior insula FC. While there was no significant correlation between subjective well-being and bilateral anterior insula FC before exercise training, a positive association between subjective well-being and bilateral anterior insula FC was found in the MCI group after exercise training. Our findings indicate that 12 weeks of exercise training may enhance subjective well-being in older adults diagnosed with MCI and, further, suggest that increased bilateral anterior insula FC with other cortical regions may reflect neural network plasticity associated with exercise training-related improvements in subjective well-being
The Contribution of Blood Serum Biomarkers to the Prediction of Cognitive Decline by fMRI and Apolipoprotein-E in Healthy Older Adults
Biomarkers are a promising approach to the prediction and early intervention of Alzheimer\u27s disease. We demonstrated that cortical functional MRI (fMRI) activation during a semantic memory task and apolipoprotein-E ?4 allele inheritance (APOE?4) effectively predicted cognitive decline after 18-months in healthy, asymptomatic elders. Hippocampal volume added modest prediction, while AD family history and demographics were ineffective. Previous studies have linked plasma homocysteine (tHcy), vitamin B12 and creatinine values to cognitive funcitoning, cortical atrophy, hippocampal atrophy and neuropathology, and vascular integrity. Here we incorporated total plasma homocysteine (tHcy), B12 creatinine values into our previous predictive models. Of 78 healthy elders, 27 (34.6%) exhibited significant cognitive decline after 18-months. tHcy, but not B12 or creatinine, was marginally positively correlated with cortical semantic memory fMRI activation, particularly in stable participants. Logistic regression showed that tHcy, when added to APOE?4 and cortical fMRI, was a significant predictor of outcome and strengthed the already significant model (p = .007; C = .80 and R2 = .37). However, control for B12 and creatinine covariates diminished tHcy as a predictor (p = .084), though the model was still stronger than without this factor (C = .78 and R = 31). tHcy did not significantly interact with APOE?4, as has previously been reported. Neither B12 nor creatinine was similarly effective as a predictor. These results suggest that commonly investigated blood serum biomarkers are at best weakly associated with predicting age- and dementia-related cognitive decline in healthy, asymptomatic elders. fMRI and APOE?4 presently provided the best predictive model
Semantic Memory Functional MRI and Cognitive Function After Exercise Intervention in Mild Cognitive Impairment
Mild cognitive impairment (MCI) is associated with early memory loss, Alzheimer\u27s disease (AD) neuropathology, inefficient or ineffective neural processing, and increased risk for AD. Unfortunately, treatments aimed at improving clinical symptoms or markers of brain function generally have been of limited value. Physical exercise is often recommended for people diagnosed with MCI, primarily because of its widely reported cognitive benefits in healthy older adults. However, it is unknown if exercise actually benefits brain function during memory retrieval in MCI. Here, we examined the effects of exercise training on semantic memory activation during functional magnetic resonance imaging (fMRI). Seventeen MCI participants and 18 cognitively intact controls, similar in sex, age, education, genetic risk, and medication use, volunteered for a 12-week exercise intervention consisting of supervised treadmill walking at a moderate intensity. Both MCI and control participants significantly increased their cardiorespiratory fitness by approximately 10% on a treadmill exercise test. Before and after the exercise intervention, participants completed an fMRI famous name discrimination task and a neuropsychological battery, Performance on Trial 1 of a list-learning task significantly improved in the MCI participants. Eleven brain regions activated during the semantic memory task showed a significant decrease in activation intensity following the intervention that was similar between groups (p-values ranged 0.048 to 0.0001). These findings suggest exercise may improve neural efficiency during semantic memory retrieval in MCI and cognitively intact older adults, and may lead to improvement in cognitive function. Clinical trials are needed to determine if exercise is effective to delay conversion to AD
The Contribution of Blood Serum Biomarkers to the Prediction of Cognitive Decline by fMRI and Apolipoprotein-E in Healthy Older Adults
Biomarkers are a promising approach to the prediction and early intervention of Alzheimer\u27s disease. We demonstrated that cortical functional MRI (fMRI) activation during a semantic memory task and apolipoprotein-E ?4 allele inheritance (APOE?4) effectively predicted cognitive decline after 18-months in healthy, asymptomatic elders. Hippocampal volume added modest prediction, while AD family history and demographics were ineffective. Previous studies have linked plasma homocysteine (tHcy), vitamin B12 and creatinine values to cognitive funcitoning, cortical atrophy, hippocampal atrophy and neuropathology, and vascular integrity. Here we incorporated total plasma homocysteine (tHcy), B12 creatinine values into our previous predictive models. Of 78 healthy elders, 27 (34.6%) exhibited significant cognitive decline after 18-months. tHcy, but not B12 or creatinine, was marginally positively correlated with cortical semantic memory fMRI activation, particularly in stable participants. Logistic regression showed that tHcy, when added to APOE?4 and cortical fMRI, was a significant predictor of outcome and strengthed the already significant model (p = .007; C = .80 and R2 = .37). However, control for B12 and creatinine covariates diminished tHcy as a predictor (p = .084), though the model was still stronger than without this factor (C = .78 and R = 31). tHcy did not significantly interact with APOE?4, as has previously been reported. Neither B12 nor creatinine was similarly effective as a predictor. These results suggest that commonly investigated blood serum biomarkers are at best weakly associated with predicting age- and dementia-related cognitive decline in healthy, asymptomatic elders. fMRI and APOE?4 presently provided the best predictive model
Functional Magnetic Resonance Imaging of Semantic Memory as a Presymptomatic Biomarker of Alzheimer’s Disease Risk
Extensive research efforts have been directed toward strategies for predicting risk of developing Alzheimer\u27s disease (AD) prior to the appearance of observable symptoms. Existing approaches for early detection of AD vary in terms of their efficacy, invasiveness, and ease of implementation. Several non-invasive magnetic resonance imaging strategies have been developed for predicting decline in cognitively healthy older adults. This review will survey a number of studies, beginning with the development of a famous name discrimination task used to identify neural regions that participate in semantic memory retrieval and to test predictions of several key theories of the role of the hippocampus in memory. This task has revealed medial temporal and neocortical contributions to recent and remote memory retrieval, and it has been used to demonstrate compensatory neural recruitment in older adults, apolipoprotein E ε4 carriers, and amnestic mild cognitive impairment patients. Recently, we have also found that the famous name discrimination task provides predictive value for forecasting episodic memory decline among asymptomatic older adults. Other studies investigating the predictive value of semantic memory tasks will also be presented. We suggest several advantages associated with the use of semantic processing tasks, particularly those based on person identification, in comparison to episodic memory tasks to study AD risk. Future directions for research and potential clinical uses of semantic memory paradigms are also discussed. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease
Motor Timing Intraindividual Variability in Amnestic Mild Cognitive Impairment and Cognitively Intact Elders at Genetic Risk for Alzheimer’s Disease
Introduction: Intraindividual variability (IIV) in motor performance has been shown to predict future cognitive decline. The apolipoprotein E-epsilon 4 (APOE-ε4) allele is also a well-established risk factor for memory decline. Here, we present novel findings examining the influence of the APOE-ε4 allele on the performance of asymptomatic healthy elders in comparison to individuals with amnestic MCI (aMCI) on a fine motor synchronization, paced finger-tapping task (PFTT).
Method: Two Alzheimer’s disease (AD) risk groups, individuals with aMCI (n = 24) and cognitively intact APOE-ε4 carriers (n = 41), and a control group consisting of cognitively intact APOE-ε4 noncarriers (n = 65) completed the Rey Auditory Verbal Learning Test and the PFTT, which requires index finger tapping in synchrony with a visual stimulus (interstimulus interval = 333 ms).
Results: Motor timing IIV, as reflected by the standard deviation of the intertap interval (ITI), was greater in the aMCI group than in the two groups of cognitively intact elders; in contrast, all three groups had statistically equivalent mean ITI. No significant IIV differences were observed between the asymptomatic APOE-ε4 carriers and noncarriers. Poorer episodic memory performance was associated with greater IIV, particularly in the aMCI group.
Conclusions: Results suggest that increased IIV on a fine motor synchronization task is apparent in aMCI. This IIV measure was not sensitive in discriminating older asymptomatic individuals at genetic risk for AD from those without such a genetic risk. In contrast, episodic memory performance, a well-established predictor of cognitive decline in preclinical AD, was able to distinguish between the two cognitively intact groups based on genetic risk
Genetic Risk for Alzheimer\u27s Disease Alters the Five-Year Trajectory of Semantic Memory Activation in Cognitively Intact Elders
Healthy aging is associated with cognitive declines typically accompanied by increased task-related brain activity in comparison to younger counterparts. The Scaffolding Theory of Aging and Cognition (STAC) (Park and Reuter-Lorenz, 2009; Reuter-Lorenz and Park, 2014) posits that compensatory brain processes are responsible for maintaining normal cognitive performance in older adults, despite accumulation of aging-related neural damage. Cross-sectional studies indicate that cognitively intact elders at genetic risk for Alzheimer\u27s disease (AD) demonstrate patterns of increased brain activity compared to low risk elders, suggesting that compensation represents an early response to AD-associated pathology. Whether this compensatory response persists or declines with the onset of cognitive impairment can only be addressed using a longitudinal design. The current prospective, 5-year longitudinal study examined brain activation in APOE ε4 carriers (N = 24) and non-carriers (N = 21). All participants, ages 65–85 and cognitively intact at study entry, underwent task-activated fMRI, structural MRI, and neuropsychological assessments at baseline, 18, and 57 months. fMRI activation was measured in response to a semantic memory task requiring participants to discriminate famous from non-famous names. Results indicated that the trajectory of change in brain activation while performing this semantic memory task differed between APOE ε4 carriers and non-carriers. The APOE ε4 group exhibited greater activation than the Low Risk group at baseline, but they subsequently showed a progressive decline in activation during the follow-up periods with corresponding emergence of episodic memory loss and hippocampal atrophy. In contrast, the non-carriers demonstrated a gradual increase in activation over the 5-year period. Our results are consistent with the STAC model by demonstrating that compensation varies with the severity of underlying neural damage and can be exhausted with the onset of cognitive symptoms and increased structural brain pathology. Our fMRI results could not be attributed to changes in task performance, group differences in cerebral perfusion, or regional cortical atrophy
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