Ping Ren

Cognitive and Neural Effects of Vision-Based Speed-of-Processing Training in Older Adults with Amnestic Mild Cognitive Impairment: A Pilot Study

To examine the cognitive and neural effects of vision‐based speed‐of‐processing (VSOP) training in older adults with amnestic mild cognitive impairment (aMCI) and contrast those effects with an active control (mental leisure activities (MLA)).

Longitudinal Alteration of Intrinsic Brain Activity in the Striatum in Mild Cognitive Impairment

The striatum is a critical functional hub in understanding neurological disorders. However, the Alzheimers disease (AD)-associated striatal change is unclear, as is the relationship between striatal change and AD pathology. Three-year resting-state fMRI data from 15 healthy control (HC) and 20 mild cognitive impairment (MCI) participants were obtained. We analyzed the amplitude of low-frequency fluctuations (ALFF) (0.01-0.08 Hz) and two subdivided bands (slow-4:0.027-0.073 Hz; slow-5:0.01-0.027 Hz). We calculated Aβ/pTau ratio using baseline cerebrospinal fluid pTau and Aβ1-42 to represent AD pathology. Compared to HC, MCI participants showed greater decline in right putaminal ALFF, including the slow-4 band. Greater decline of ALFF in the right putamen was significantly related to the memory decline over time and lower baseline Aβ/pTau ratio regardless of age or group. The slow-4 band, relative to slow-5 band, showed a stronger correlation between Aβ/pTau ratio and decline of ALFF in the right putamen. The results suggest that the putaminal function declines early in the AD-associated neurodegeneration. The continuous decline in putaminal ALFF, especially slow-4 band, may be a sensitive marker of AD pathology such as Aβ/pTau ratio regardless of clinical diagnosis.

Insula and Inferior Frontal Gyrus' Activities Protect Memory Performance Against Alzheimer's Disease Pathology in Old Age.

Apolipoprotein E (APOE) ɛ4 carriers and patients with amnestic mild cognitive impairment (MCI) have high risk of developing Alzheimers disease (AD). The Scaffolding Theory of Aging and Cognition proposes that recruitment of additional frontal brain regions can protect cognition against aging. This thesis has yet to be fully tested in older adults at high risk for AD. In the present study, 75 older participants (mean age: 74 years) were included. Applying a voxel-wise approach, fractional amplitude of low-frequency fluctuations (fALFF) in resting-state functional neuroimaging data were analyzed as a function of APOEɛ4 status (carrier versus noncarrier) and clinical status (healthy control [HC] versus MCI) using a 2×2 analysis of covariance (ANCOVA). Measures of cognition and cerebrospinal fluid levels of amyloid- β were also obtained. Three frontal regions were identified with significant interaction effects using ANCOVA (corrected p < 0.01): left-insula, left-inferior frontal gyrus (IFG), and right-precentral gyrus. The HC/APOEɛ4 carrier group had significantly higher fALFF in all three regions than other groups. In the entire sample, for two regions (left insula and left IFG), a significant positive relationship between amyloid-β and memory was only observed among individuals with low fALFF. Our results suggest higher activity in frontal regions may explain being cognitively normal among a subgroup of APOEɛ4 carriers and protect against the negative impact of AD-associated pathology on memory. This is an observation with potential implications for AD therapeutics.

A Role of the Parasympathetic Nervous System in Cognitive Training

BACKGROUND Vision-based speed of processing (VSOP) training can result in broad cognitive improvements in older adults with amnestic mild cognitive impairment (aMCI). What remains unknown, however, is what neurophysiological mechanisms account for the observed training effect. Much of the work in this area has focused on the central nervous system, neglecting the fact that the peripheral system can contributes to changes of the central nervous system and vice versa. OBJECTIVE We examined the prospective relationship between an adaptive parasympathetic nervous system response to cognitive stimuli and VSOP training-induced plasticity. METHOD Twenty-one participants with aMCI (10 for VSOP training, and 11 for mental leisure activities (MLA) control) were enrolled. We assessed high-frequency heart rate variability (HF-HRV) during training sessions, and striatum-related neural networks and cognition at baseline and post-training. RESULTS Compared to MLA, the VSOP group showed a significant U-shaped pattern of HF-HRV response during training, as well as decreases in connectivity strength between bilateral striatal and prefrontal regions. These two effects were associated with training-induced improvements in both the trained (attention and processing speed) and transferred (working memory) cognitive domains. CONCLUSION This work provides novel support for interactions between the central and the peripheral nervous systems in relation to cognitive training, and motivates further studies to elucidate the causality of the observed link.

Amygdala functional connectivity is associated with locus of control in the context of cognitive aging

ABSTRACT Locus of control (LOC) measures the extent to which individuals perceive control over their lives. Those with a more “internal” LOC feel self‐sufficient and able to determine important aspects of their own future, while those with a more “external” LOC feel that their lives are governed by events beyond their control. Reduced internal LOC and increased external LOC have been found in cognitive disorders, but the neural substrates of these control perceptions are yet unknown. In the present study, we explored the relationship between amygdala functional connectivity and LOC in 18 amnestic mild cognitive impairment (MCI) and age‐, sex‐, and education‐matched, 22 cognitively healthy controls (HC). Participants completed cognitive challenge tasks (Stroop Word Color task and Dual 1‐back) for 20 min, and underwent resting‐state functional magnetic resonance imaging immediately before and after the tasks. We found significantly lower internal LOC and higher external LOC in the MCI group than the HC group. Compared to HC, MCI group showed significantly stronger positive associations between internal LOC and baseline right amygdala connections (including right middle frontal gyrus and anterior cingulate cortex), and stronger negative associations between internal LOC and change of these right amygdala connections. Across all participants, external LOC explained the relationships between associations of another set of right amygdala connections (including middle cingulate cortex and right superior frontal gyrus), both at baseline and for change, and performance in the cognitive challenge tasks. Our findings indicate that the right amygdala networks might be critical in understanding the neural mechanisms underlying LOCs role in cognitive aging. HIGHLIGHTSMCI group had lower internal LOC while higher external LOC than HC.Higher internal LOC linked to greater baseline amygdala network in MCI.Higher internal LOC linked to less amygdala network change after challenge in MCI.External LOC explained amygdala networks link with cognitive performance.

INSULAR ACTIVITY PROTECTS MEMORY PERFORMANCE AGAINST ALZHEIMER’S PATHOLOGY AMONG HIGH-RISK OLDER ADULTS

Background:The hippocampal formation is a complex and highly organized brain structure. The gross volume of the hippocampus has been related to various cognitive functions as well as the risk of dementia. However, it remains unknown whether certain subfields are primarily driving these associations.Methods:We studied 4,768 non-demented and stroke-free persons from the Rotterdam study, a prospective population-based cohort in the elderly (>1⁄445 years). All participants underwent magnetic resonance imaging (1.5T) followed by automatic segmentation of the hippocampus and its subfields using the FreeSurfer software (version 6.0). A cognitive test battery was used to assess executive functioning, fine motor speed, information processing, and memory, as well as a combined measure of general cognitive function. Subsequently, persons were followed up for the development of dementia. The association of the hippocampal subfields with cognition and incident dementia was tested using linear and Cox regression models, respectively. All analyses were adjusted for age, sex, education, MMSE, and the gross volume of the hippocampus. Results:Mean age was 68.9 (SD 10.9) and 55.5% were women. The volume of the hippocampal CA1 region, fimbria, fissure, and subiculum were among the structures that showed the most significant associations with all cognitive domains, except memory (Table 1). During a mean follow-up of 5.5 years, 76 persons became demented. Subiculum volume, particularly of the right hippocampus, was associated with risk of dementia (Table 1). Conclusions:The subfields of the hippocampus provide additional information beyond its gross volume for various aspects of cognitive functioning, but surprisingly not for memory. Furthermore, our results suggest that the subiculum could be an important marker for predicting dementia.

Functional and structural connectivity of the amygdala underpins locus of control in mild cognitive impairment

Locus of control (LOC) is an important personality trait. LOC over cognitive competency reflects an individuals perceived control of desired cognitive outcomes, which is critical for maintaining successful cognitive aging. It is important to understand the neural substrates of LOC over cognitive competency in older adults, especially for individuals at high risk of dementia. Here, we characterized a cohesive functional and structural connectivity profile underlying LOC among 55 older adults with amnestic mild cognitive impairment (aMCI), combining resting-state functional magnetic resonance imaging and diffusion tensor imaging. The results showed that both functional and structural connectivity between the medial prefrontal cortex and amygdala were significantly correlated with external LOC. The functional connectivity mediated the correlation between structural connectivity and external LOC. In addition, aging-associated neurodegeneration moderated the relationship between structural connectivity and external LOC, showing that the structural connectivity was positively correlated with external LOC in low, but not high neurodegeneration. Our results suggest a critical role of the functional amygdala-frontal network, which may serve as a bridge between its white matter tract and LOC over cognitive competency in groups at high risk for dementia.

Cortical thickness is associated with altered autonomic function in cognitively impaired and non‐impaired older adults

The parasympathetic nervous system (PNS) is critical for adaptation to environment demands. Alzheimers disease (AD), via frontal compensatory processes, may affect PNS regulation, thereby compromising older adults’ capacity for adaptation, and increasing morbidity and mortality risk. Here we found that AD‐associated neurodegeneration accompanied an overactive anterior cingulate cortex, which in turn resulted in a high level of PNS activity at rest, as well as strong PNS activity withdrawal in response to the mental effort. This discovery provides the first line of evidence to suggest that AD‐associated neurodegeneration links to altered PNS regulation during mental effort in older adults, and that the compensatory processes accompanying frontal hyperactivation appear to be responsible for these alterations.

GLYCEMIC STATES MODULATE CORTICAL THICKNESS AND STRUCTURAL CONNECTIVITY IN OLD AGE

years of education, being 59.0% female underwent 3 Tesla MRI scans with 3DT1 acquisition. From the whole sample, 45 had dementia, 26 had cognitive impairment no-dementia and 112 were cognitively healthy. The images were processed in SPM 12. Hippocampi volumes were extracted, along with other brain cortical areas important to memory using the Neuromorphometrics atlas. Multivariate linear regression was conducted with the verbal-visual episodic memory test (the delayed recall task of the Brief Cognitive Battery) as a dependent variable and the left hippocampal volume as the predictor valuable, controlling for age, the test’s learning task, the Mini-Mental State Examination (MMSE) and the sum of the other cortical regions. The same analysis was conducted after splitting the sample in low education (<4 years of education) and relatively high education (>1⁄44 years) groups. Results:The multivariate regression model explained 68.2% of the variation on the performance on the memory test, and the left hippocampus was significantly associated, along with the learning phase of the test, the MMSE and education. The model explained 60.2% in the low educated group and 74.0% in the high educated. Furthermore, the left hippocampus was significantly more associated with the performance on memory on the high educated group. Conclusions:Education can modulate the role of the left hippocampus on episodic memory performance, even at low levels (>1⁄44 years). Further studies with brain structural connectivity can clarify if these findings reflect different structural patterns of network organization related to episodic memory processing.

Mental Fatigability and Heart Rate Variability in Mild Cognitive Impairment

OBJECTIVES Adaptive physiological stress regulation is rarely studied in mild cognitive impairment (MCI). Here we targeted mental fatigability (MF) as a determinant of altered high frequency heart rate variability (HF-HRV) reactivity in individuals with MCI, and examined frontobasal ganglia circuitry as a neural basis supporting the link between MF and HF-HRV reactivity. METHODS We measured mental fatigability and HF-HRV during a 60-minute cognitive stress protocol in 19 individuals with MCI. HF-HRV responses were modeled using a quadratic equation. Resting state functional connectivity of intra- and inter-network frontobasal ganglia circuitry was assessed using blood-oxygen-level-dependent magnetic resonance imaging among seven of the participants. RESULTS Lower MF was associated with faster and greater rebound in U-shape HF-HRV reactivity, which linked to a stronger connectivity between right middle frontal gyrus and left putamen. CONCLUSIONS Results suggest that MF may contribute to abnormal physiological stress regulation in MCI, and fronto basal ganglia circuitry may support the link.