Event-related Potentials Corresponding to Decision-making Under Uncertain Conditions.

BACKGROUND: Decision-making is essential to human functioning, and resolving uncertainty is an essential part of decision-making. Impaired decision-making is present in many pathological conditions, and identifying markers of decision-making under uncertainty will provide a measure of clinical impact in future studies of therapeutic intervention for impaired decision-making. OBJECTIVE: To describe EEG event-related potentials (ERPs) correlating with decision-making under uncertain conditions when compared with certain conditions. METHOD: We used a novel card-matching task based on the Wisconsin Card Sorting Test to describe the neural correlates of uncertainty, as measured by EEG, in a group of 27 neurotypical individuals. We evaluated 500-ms intervals in the 2 seconds after card presentation to identify ERPs that are associated with maximal uncertainty compared with maximal certainty. RESULTS: After correcting for multiple comparisons, we identified an ERP in the 500-1000-ms time frame (certain > uncertain, max amplitude 12.73 µV, latency 914 ms) in the left posterior inferior region of the scalp. We also found a P300-like ERP in the left frontal and parietal regions in the 0-500-ms time frame when the individuals received correct versus incorrect feedback (incorrect feedback > correct feedback, max amplitude 1.625 µV, latency 339 ms). CONCLUSION: We identified an ERP in the 500-1000-ms time frame (certain > uncertain) that may reflect the resolution of uncertainty, as well as a P300-like ERP when feedback is presented (incorrect feedback > correct feedback). These findings can be used in future studies to improve decision-making and resolve uncertainty on the described markers.

Corticosterone potentiates DFP-induced neuroinflammation and affects high-order diffusion imaging in a rat model of Gulf War Illness.

Veterans of the 1991 Gulf War were potentially exposed to a variety of toxic chemicals, including sarin nerve agent and pesticides, which have been suspected to be involved in the development of Gulf War Illness (GWI). Several of these exposures cause a neuroinflammatory response in mice, which may serve as a basis for the sickness behavior-like symptoms seen in veterans with GWI. Furthermore, conditions mimicking the physiological stress experienced during the war can exacerbate this effect. While neuroinflammation has been observed post-exposure using animal models, it remains a challenge to evaluate neuroinflammation and its associated cellular and molecular changes in vivo in veterans with GWI. Here, we evaluated neuroimmune-associated alterations in intact brains, applying our existing GWI mouse model to rats, by exposing them to 4days of corticosterone (CORT; 200mg/L in the drinking water), to mimic high physiological stress, followed by a single injection of the sarin nerve agent surrogate, diisopropyl fluorophosphate (DFP; 1.5mg/kg, i.p.). Then, we evaluated the neuroinflammatory responses using qPCR of cytokine mRNA and also examined brain structure with a novel high-order diffusion MRI. We found a CORT-enhancement of DFP-induced neuroinflammation, extending our mouse GWI model to the rat. High order diffusion MRI revealed different patterns among the different treatment groups. Particularly, while the CORT+DFP rats had more restricted spatial patterns in the hippocampus and the hypothalamus, the highest and most wide-spread differences were shown in DFP-treated rats compared to the controls in the thalamus, the amygdala, the piriform cortex and the ventral tegmental area. The association of these diffusion changes with neuroinflammatory cytokine expression indicates the potential for GW-relevant exposures to result in connectivity changes in the brain. By transferring this high order diffusion MRI into in vivo imaging in veterans with GWI, we can achieve further insights on the trajectories of the neuroimmune response over time and its impacts on behavior and potential neurological damage.

Retained executive abilities in mild cognitive impairment are associated with increased white matter network connectivity.

PURPOSE: To describe structural network differences in individuals with mild cognitive impairment (MCI) with high versus low executive abilities, as reflected by measures of white matter connectivity using diffusion tensor imaging (DTI). MATERIALS AND METHODS: This was a retrospective, cross-sectional study. Of the 128 participants from the Alzheimer's Disease Neuroimaging Initiative database who had both a DTI scan as well as a diagnosis of MCI, we used an executive function score to classify the top 15 scoring patients as high executive ability, and the bottom-scoring 16 patients as low executive ability. Using a regions-of-interest-based analysis, we constructed networks and calculated graph theory measures on the constructed networks. We used automated tractography in order to compare differences in major white matter tracts. RESULTS: The high executive ability group yielded greater network size, density and clustering coefficient. The high executive ability group reflected greater fractional anisotropy bilaterally in the inferior and superior longitudinal fasciculi. CONCLUSIONS: The network measures of the high executive ability group demonstrated greater white matter integrity. This suggests that white matter reserve may confer greater protection of executive abilities. Loss of this reserve may lead to greater impairment in the progression to Alzheimer's disease dementia. KEY POINTS: • The MCI high executive ability group yielded a larger network. • The MCI high executive ability group had greater FA in numerous tracts. • White matter reserve may confer greater protection of executive abilities. • Loss of executive reserve may lead to greater impairment in AD dementia.

Functional brain networks involved in decision-making under certain and uncertain conditions.

PURPOSE: The aim of this study was to describe imaging markers of decision-making under uncertain conditions in normal individuals, in order to provide baseline activity to compare to impaired decision-making in pathological states. METHODS: In this cross-sectional study, 19 healthy subjects ages 18-35 completed a novel decision-making card-matching task using a Phillips T3 Scanner and a 32-channel head coil. Functional data were collected in six functional runs. In one condition of the task, the participant was certain of the rule to apply to match the cards; in the other condition, the participant was uncertain. We performed cluster-based comparison of the two conditions using FSL fMRI Expert Analysis Tool and network-based analysis using MATLAB. RESULTS: The uncertain > certain comparison yielded three clusters-a midline cluster that extended through the midbrain, the thalamus, bilateral prefrontal cortex, the striatum, and bilateral parietal/occipital clusters. The certain > uncertain comparison yielded bilateral clusters in the insula, parietal and temporal lobe, as well as a medial frontal cluster. A larger, more connected functional network was found in the uncertain condition. CONCLUSION: The involvement of the insula, parietal cortex, temporal cortex, ventromedial prefrontal cortex, and orbitofrontal cortex of the certain condition reinforces the notion that certainty is inherently rewarding. For the uncertain condition, the involvement of the prefrontal cortex, parietal cortex, striatum, thalamus, amygdala, and hippocampal involvement was expected, as these are areas involved in resolving uncertainty and rule updating. The involvement of occipital cortical involvement and midbrain involvement may be attributed to increased visual attention and increased motor control.

Delphi definition of the EADC-ADNI Harmonized Protocol for hippocampal segmentation on magnetic resonance.

BACKGROUND: This study aimed to have international experts converge on a harmonized definition of whole hippocampus boundaries and segmentation procedures, to define standard operating procedures for magnetic resonance (MR)-based manual hippocampal segmentation. METHODS: The panel received a questionnaire regarding whole hippocampus boundaries and segmentation procedures. Quantitative information was supplied to allow evidence-based answers. A recursive and anonymous Delphi procedure was used to achieve convergence. Significance of agreement among panelists was assessed by exact probability on Fisher's and binomial tests. RESULTS: Agreement was significant on the inclusion of alveus/fimbria (P = .021), whole hippocampal tail (P = .013), medial border of the body according to visible morphology (P = .0006), and on this combined set of features (P = .001). This definition captures 100% of hippocampal tissue, 100% of Alzheimer's disease-related atrophy, and demonstrated good reliability on preliminary intrarater (0.98) and inter-rater (0.94) estimates. DISCUSSION: Consensus was achieved among international experts with respect to hippocampal segmentation using MR resulting in a harmonized segmentation protocol.

The EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: evidence of validity.

BACKGROUND: An international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance. METHODS: Fourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T. RESULTS: The agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P < .001), and physiological variability (49.2%, P < .001). CONCLUSIONS: The HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms.

Brain age of rhesus macaques over the lifespan.

Through the application of machine learning algorithms to neuroimaging data the brain age methodology was shown to provide a useful individual-level biological age prediction and identify key brain regions responsible for the prediction. In this study, we present the methodology of constructing a rhesus macaque brain age model using a machine learning algorithm and discuss the key predictive brain regions in comparison to the human brain, to shed light on cross-species primate similarities and differences. Structural information of the brain (e.g., parcellated volumes) from brain magnetic resonance imaging of 43 rhesus macaques were used to develop brain atlas-based features to build a brain age model that predicts biological age. The best-performing model used 22 selected features and achieved an R2 of 0.72. We also identified interpretable predictive brain features including Right Fronto-orbital Cortex, Right Frontal Pole, Right Inferior Lateral Parietal Cortex, and Bilateral Posterior Central Operculum. Our findings provide converging evidence of the parallel and comparable brain regions responsible for both non-human primates and human biological age prediction.

Hippocampal network connections account for differences in memory performance in the middle-aged rhesus monkey.

Recent neurophysiological and functional neuroimaging studies suggest that the memory decline found with normal aging is not solely due to regional disruptions in the hippocampus, but also is brought about by alterations in the functional coupling between the hippocampus and long-distance neocortical regions. However, the anatomical basis for this functional "dyscoupling" has not been fully revealed. In this study, we applied a multimodal magnetic resonance imaging technique to noninvasively examine the large-scale anatomical and functional hippocampal network of a group of middle aged rhesus monkeys. Using diffusion spectrum imaging, we have found that monkeys with lower memory performance had weaker structural white matter connections between the hippocampus and neocortical association areas. Resting state functional imaging revealed somewhat of an opposite result. Monkeys with low memory performance displayed elevated coupling strengths in the network between the hippocampus and the neocortical areas. Taken together with recent findings, this contradictory pattern may be the result of either underlying physiological burden or abnormal neuronal decoupling due to the structural alterations, which induce a neuronal compensation mechanism for the structural loss or interference on task related neuronal activation, respectively.

Recovery of fine motor performance after ischemic damage to motor cortex is facilitated by cell therapy in the rhesus monkey.

We investigated the efficacy on recovery of function following controlled cortical ischemia in the monkey of the investigational cell drug product, CNTO 0007. This drug contains a cellular component, human umbilical tissue-derived cells, in a proprietary thaw and inject formulation. Results demonstrate significantly better recovery of motor function in the treatment group with no difference between groups in the volume or surface area of ischemic damage, suggesting that the cells stimulated plasticity.

Standardization of analysis sets for reporting results from ADNI MRI data.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) three-dimensional T1-weighted magnetic resonance imaging (MRI) acquisitions provide a rich data set for developing and testing analysis techniques for extracting structural endpoints. To promote greater rigor in analysis and meaningful comparison of different algorithms, the ADNI MRI Core has created standardized analysis sets of data comprising scans that met minimum quality control requirements. We encourage researchers to test and report their techniques against these data. Standard analysis sets of volumetric scans from ADNI-1 have been created, comprising screening visits, 1-year completers (subjects who all have screening, 6- and 12-month scans), 2-year annual completers (screening, 1-year and 2-year scans), 2-year completers (screening, 6-months, 1-year, 18-months [mild cognitive impaired (MCI) only], and 2-year scans), and complete visits (screening, 6-month, 1-year, 18-month [MCI only], 2-year, and 3-year [normal and MCI only] scans). As the ADNI-GO/ADNI-2 data become available, updated standard analysis sets will be posted regularly.

Prefrontal and medial temporal interactions in memory functions in the rhesus monkey.

Both the medial temporal lobe and the dorsolateral prefrontal cortex have been implicated in learning and memory. However, it has been difficult to ascertain the degree to which the two structures are dependent on each other or interact in subserving these cognitive functions. To investigate this question directly, we prepared two group of monkeys. First, the contralateral frontal-hippocampal split group (CFHS) received a unilateral lesion of the hippocampus and surrounding posterior parahippocampal cortices (H +), combined with a contralateral lesion of the dorsolateral prefrontal cortex (DLPFC) plus transection of the corpus callosum and anterior commissure. This preparation functionally "disconnects" the remaining intact H + from the sole intact DLPFC in the opposite hemisphere. As a surgical control group, a second set of animals, the ipsilateral frontal-hippocampal split group, was prepared with a unilateral lesion of the DLPFC and an ipsilateral H + lesion together plus transection of the corpus callosum and anterior commissure. This preparation matches the locus and extent of damage in the cross-lesion group but allows the intact H + and intact DLPFC to interact ipsilaterally. Following recovery from surgery, all animals were then tested on the delayed nonmatching to sample task (DNMS), a test of recognition memory. The crossed-lesion split-brain group (CFHS) was markedly impaired on DNMS in both acquisition (rule learning) and performance over delays (recognition memory). The results provide evidence of a functionally dependent interaction between the medial temporal lobe and the dorsolateral prefrontal cortex in learning and memory. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neuronal properties of pyramidal cells in lateral prefrontal cortex of the aging rhesus monkey brain are associated with performance deficits on spatial working memory but not executive function.

Age-related declines in cognitive abilities occur as early as middle-age in humans and rhesus monkeys. Specifically, performance by aged individuals on tasks of executive function (EF) and working memory (WM) is characterized by greater frequency of errors, shorter memory spans, increased frequency of perseverative responses, impaired use of feedback and reduced speed of processing. However, how aging precisely differentially impacts specific aspects of these cognitive functions and the distinct brain areas mediating cognition are not well understood. The prefrontal cortex (PFC) is known to mediate EF and WM and is an area that shows a vulnerability to age-related alterations in neuronal morphology. In the current study, we show that performance on EF and WM tasks exhibited significant changes with age, and these impairments correlate with changes in biophysical properties of layer 3 (L3) pyramidal neurons in lateral LPFC (LPFC). Specifically, there was a significant age-related increase in excitability of L3 LPFC pyramidal neurons, consistent with previous studies. Further, this age-related hyperexcitability of LPFC neurons was significantly correlated with age-related decline on a task of WM, but not an EF task. The current study characterizes age-related performance on tasks of WM and EF and provides insight into the neural substrates that may underlie changes in both WM and EF with age.

Associations between white matter integrity of the cingulum bundle, surrounding gray matter regions, and cognition across the dementia continuum.

INTRODUCTION: Previous Alzheimer's disease and related dementias (AD/ADRD) research studies have illustrated the significance of studying alterations in white matter (WM). Fewer studies have examined how WM integrity, measured with diffusion tensor imaging (DTI), is associated with volume of gray matter (GM) regions and measures of cognitive function in aged participants spanning the dementia continuum. METHODS: Magnetic resonance imaging and cognitive data were collected from 241 Boston University Alzheimer's Disease Research Center participants who spanned from cognitively normal controls to amnestic mild cognitive impairment to having dementia. Primary DTI tracts of interest were the cingulum ventral (CV) and cingulum dorsal (CD) pathways. GM regions of interest (ROIs) were in the medial temporal lobe (MTL), prefrontal cortex, and retrosplenial cortex. Analyses of covariance models were used to assess differences in WM integrity across groups (control, amnestic mild cognitive impairment, and dementia). Multiple linear regression models were used to assess associations between WM integrity and GM volume, and with measures of memory and executive function. RESULTS: Differences in WM integrity were shown in both cingulum pathways in participants across the dementia continuum. Associations between WM integrity of both cingulum pathways and volume of selected GM ROIs were widespread. Functionally significant associations were found between WM of the CV pathway and memory, independent of MTL GM volume. DISCUSSION: Differences in WM integrity of the cingulum bundle and surrounding GM ROI are likely related to the progression of AD/ADRD. Such differences should continue to be studied, particularly in association with memory performance.

Human-to-monkey transfer learning identifies the frontal white matter as a key determinant for predicting monkey brain age.

The application of artificial intelligence (AI) to summarize a whole-brain magnetic resonance image (MRI) into an effective "brain age" metric can provide a holistic, individualized, and objective view of how the brain interacts with various factors (e.g., genetics and lifestyle) during aging. Brain age predictions using deep learning (DL) have been widely used to quantify the developmental status of human brains, but their wider application to serve biomedical purposes is under criticism for requiring large samples and complicated interpretability. Animal models, i.e., rhesus monkeys, have offered a unique lens to understand the human brain - being a species in which aging patterns are similar, for which environmental and lifestyle factors are more readily controlled. However, applying DL methods in animal models suffers from data insufficiency as the availability of animal brain MRIs is limited compared to many thousands of human MRIs. We showed that transfer learning can mitigate the sample size problem, where transferring the pre-trained AI models from 8,859 human brain MRIs improved monkey brain age estimation accuracy and stability. The highest accuracy and stability occurred when transferring the 3D ResNet [mean absolute error (MAE) = 1.83 years] and the 2D global-local transformer (MAE = 1.92 years) models. Our models identified the frontal white matter as the most important feature for monkey brain age predictions, which is consistent with previous histological findings. This first DL-based, anatomically interpretable, and adaptive brain age estimator could broaden the application of AI techniques to various animal or disease samples and widen opportunities for research in non-human primate brains across the lifespan.

The prevalence of mild cognitive impairment in Gulf War veterans: a follow-up study.

Introduction: Gulf War Illness (GWI), also called Chronic Multisymptom Illness (CMI), is a multi-faceted condition that plagues an estimated 250,000 Gulf War (GW) veterans. Symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. We previously reported that 12% of a convenience sample of middle aged (median age 52 years) GW veterans met criteria for mild cognitive impairment (MCI), a clinical syndrome most prevalent in older adults (e.g., ≥70 years). The current study sought to replicate and extend this finding. Methods: We used the actuarial neuropsychological criteria and the Montreal Cognitive Assessment (MoCA) to assess the cognitive status of 952 GW veterans. We also examined regional brain volumes in a subset of GW veterans (n = 368) who had three Tesla magnetic resonance images (MRIs). Results: We replicated our previous finding of a greater than 10% rate of MCI in four additional cohorts of GW veterans. In the combined sample of 952 GW veterans (median age 51 years at time of cognitive testing), 17% met criteria for MCI. Veterans classified as MCI were more likely to have CMI, history of depression, and prolonged (≥31 days) deployment-related exposures to smoke from oil well fires and chemical nerve agents compared to veterans with unimpaired and intermediate cognitive status. We also replicated our previous finding of hippocampal atrophy in veterans with MCI, and found significant group differences in lateral ventricle volumes. Discussion: Because MCI increases the risk for late-life dementia and impacts quality of life, it may be prudent to counsel GW veterans with cognitive dysfunction, CMI, history of depression, and high levels of exposures to deployment-related toxicants to adopt lifestyle habits that have been associated with lowering dementia risk. With the Food and Drug Administration's recent approval of and the VA's decision to cover the cost for anti-amyloid ß (Aß) therapies, a logical next step for this research is to determine if GW veterans with MCI have elevated Aß in their brains.

Neuronal properties of pyramidal cells in lateral prefrontal cortex of the aging rhesus monkey brain are associated with performance deficits on spatial working memory but not executive function.

Age-related declines in cognitive abilities occur as early as middle-age in humans and rhesus monkeys. Specifically, performance by aged individuals on tasks of executive function (EF) and working memory (WM) is characterized by greater frequency of errors, shorter memory spans, increased frequency of perseverative responses, impaired use of feedback and reduced speed of processing. However, how aging precisely differentially impacts specific aspects of these cognitive functions and the distinct brain areas mediating cognition are not well understood. The prefrontal cortex (PFC) is known to mediate EF and WM and is an area that shows a vulnerability to age-related alterations in neuronal morphology. In the current study, we show that performance on EF and WM tasks exhibited significant changes with age and these impairments correlate with changes in biophysical properties of L3 pyramidal neurons in lateral LPFC (LPFC). Specifically, there was a significant age-related increase in excitability of Layer 3 LPFC pyramidal neurons, consistent with previous studies. Further, this age-related hyperexcitability of LPFC neurons was significantly correlated with age-related decline on a task of WM, but not an EF task. The current study characterizes age-related performance on tasks of WM and EF and provides insight into the neural substrates that may underlie changes in both WM and EF with age.

Biomarkers of Alzheimer's disease in Black and/or African American Alzheimer's Disease Neuroimaging Initiative (ADNI) participants.

Majority of dementia research is conducted in non-Hispanic White participants despite a greater prevalence of dementia in other racial groups. To obtain a better understanding of biomarker presentation of Alzheimer's disease (AD) in the non-Hispanic White population, this study exclusively examined AD biomarker abnormalities in 85 Black and/or African American participants within the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants were classified by the ADNI into 3 clinical groups: cognitively normal, mild cognitive impairment, or dementia. Data examined included demographics, apolipoprotein E (APOE) ε4, cerebrospinal fluid (CSF) Aß1-42, CSF total tau (t-tau), CSF phosphorylated tau (p-tau), 3T magnetic resonance imaging (MRI), and measures of cognition and function. Analyses of variance and covariance showed lower cortical thickness in 5 of 7 selected MRI regions, lower hippocampal volume, greater volume of white matter hyperintensities, lower measures of cognition and function, lower measures of CSF Aß1-42, and greater measures of CSF t-tau and p-tau between clinical groups. Our findings confirmed greater AD biomarker abnormalities between clinical groups in this sample.

Identification of an APOE ε4-specific blood-based molecular pathway for Alzheimer's disease risk.

INTRODUCTION: The precise apolipoprotein E (APOE) ε4-specific molecular pathway(s) for Alzheimer's disease (AD) risk are unclear. METHODS: Plasma protein modules/cascades were analyzed using weighted gene co-expression network analysis (WGCNA) in the Alzheimer's Disease Neuroimaging Initiative study. Multivariable regression analyses were used to examine the associations among protein modules, AD diagnoses, cerebrospinal fluid (CSF) phosphorylated tau (p-tau), and brain glucose metabolism, stratified by APOE genotype. RESULTS: The Green Module was associated with AD diagnosis in APOE ε4 homozygotes. Three proteins from this module, C-reactive protein (CRP), complement C3, and complement factor H (CFH), had dose-dependent associations with CSF p-tau and cognitive impairment only in APOE ε4 homozygotes. The link among these three proteins and glucose hypometabolism was observed in brain regions of the default mode network (DMN) in APOE ε4 homozygotes. A Framingham Heart Study validation study supported the findings for AD. DISCUSSION: The study identifies the APOE ε4-specific CRP-C3-CFH inflammation pathway for AD, suggesting potential drug targets for the disease.Highlights: Identification of an APOE ε4 specific molecular pathway involving blood CRP, C3, and CFH for the risk of AD.CRP, C3, and CFH had dose-dependent associations with CSF p-Tau and brain glucose hypometabolism as well as with cognitive impairment only in APOE ε4 homozygotes.Targeting CRP, C3, and CFH may be protective and therapeutic for AD onset in APOE ε4 carriers.

Annualized changes in rate of amyloid deposition and neurodegeneration are greater in participants who become amyloid positive than those who remain amyloid negative.

This study longitudinally examined participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who underwent a conversion in amyloid-beta (Aß) status in comparison to a group of ADNI participants who did not show a change in amyloid status over the same follow-up period. Participants included 136 ADNI dementia-free participants with 2 florbetapir positron emission tomography (PET) scans. Of these participants, 68 showed amyloid conversion as measured on florbetapir PET, and the other 68 did not. Amyloid converters and non-converters were chosen to have representative demographic data (age, education, sex, diagnostic status, and race). The amyloid converter group showed increased prevalence of APOE ε4 (p < 0.001), greater annualized percent volume loss in selected magnetic resonance imaging (MRI) regions (p < 0.05), lower cerebrospinal fluid Aß1-42 (p < 0.001), and greater amyloid retention (as measured by standard uptake value ratios) on florbetapir PET scans (p < 0.001) in comparison to the non-converter group. These results provide compelling evidence that important neuropathological changes are occurring alongside amyloid conversion.

Curcumin improves reversal learning in middle-aged rhesus monkeys.

Age-related impairments in cognitive function occur in multiple animal species including humans and nonhuman primates. Humans and rhesus monkeys exhibit a similar pattern of cognitive decline beginning in middle age, particularly within the domain of executive function. The prefrontal cortex is the brain region most closely associated with mediating executive function. Previous studies in rhesus monkeys have demonstrated that normal aging leads to an increase in myelin degradation in the prefrontal regions that correlates with cognitive decline. This myelin deterioration is thought to result, at least in part, from the age-related emergence of chronic low levels of inflammation. One therapeutic that may arrest the deleterious effects of neuroinflammation is curcumin (CUR), the primary component of the spice turmeric. CUR has been shown to be a potent anti-inflammatory and antioxidant and improves performance on tasks for working memory and motor function. In the present study, middle-aged monkeys (12-21 years old) were given daily dietary supplementation of 500 mg of curcumin or vehicle over a period of 3-4 years. Here, we present data from a series of both object and spatial reversal tasks. Compared to vehicle, the CUR group showed enhanced performance on object, but not spatial reversal learning. These findings suggest that curcumin may improve specific aspects of executive function. (PsycInfo Database Record (c) 2022 APA, all rights reserved).