Cognitive Decrements Research Articles

0171 The Impact of Short-Term Bright Green Light Exposure in Partially Sleep-Deprived Persons

Abstract Introduction Many workers and students experience regular sleep deprivation and daytime sleepiness when they are expected to be performing at their best. The purpose of the current research was to investigate the potential effect of short-term bright green light exposure on daytime performance and sleepiness in partially sleep-deprived persons. Methods Participants were 30 students (19.4±0.89 years; 20 females). On Day 1, participants were loaned a Fitbit to provide an objective measure of activity/sleep and were instructed to sleep no more than 5 hours that night. On Day 2, participants provided information on their sleep time for the previous night and were randomly assigned to a bright light condition (bright green light, 381 Lux) or a standard light condition (control condition, indoor florescent light, 139 Lux). They completed a simple reaction time task, the Arrow Flankers task to measure cognitive inhibition, and the Stanford Sleepiness Scale during three testing periods (baseline, after 20 minutes of light exposure, and after 60 minutes of light exposure). Between the testing periods, participants read a non-fiction book while exposed to their respective light condition. At the end of the study, participants returned their FitBit. Results The Fitbit and self-report sleep data indicated that participants slept 4.9 hours the night between Day 1 and Day 2. Mixed 2 (light condition) x 3 (testing period) ANOVAs indicated that the bright green light condition resulted in a significant decrease in reaction time on the Flankers task but had no significant effect on simple reaction time or subjective sleepiness. Conclusion The current findings suggest that 60 minutes of bright green light exposure could improve performance on a cognitive inhibition task. This suggests that bright green light exposure could be a useful countermeasure for cognitive performance decrements in settings where sleep deprivation is common. Support None to report.

0055 Physiological Based Predictive Models of Vigilance

Abstract Introduction The Naval Submarine Medical Research Laboratory (NSMRL) is developing predictive models to examine how non-invasive, non-disruptive physiological monitoring can be used to track performance decrements due to sleep deficiency. Utilizing biometrics extracted from physiological measures to track performance changes would allow for automated tracking of fatigue and alleviate the overhead necessary to monitor individual schedules and sleep patterns. Methods NSMRL collaborated with the University of Connecticut to run a sleep deprivation study that deprived 20 participants of sleep for a period of up to 25 hours. During this time, subjects completed multiple tasks, including the Psychomotor Vigilance Test (PVT) every few hours. A non-invasive monitoring system collected physiological data from participants, which includes eye tracking, electrocardiography, electrodermal activity, and facial tracking (e.g., blink metrics, heart rate variability, skin conductance levels, facial action units). Using this multimodal approach, biometrics were extracted and evaluated to determine their predictive power on PVT performance. Multiple linear regression, using predictors selected via sequential forward selection, was used to develop a model of performance at an individual level based on a subset of these metrics chosen using principal component regression. Results Thirty-eight biometrics were extracted from the collected data and used to produce a predictive model of PVT performance. Sequential forward selection was used to select 11 primary biometrics. The criteria for primary metric inclusion in the model was minimization of root mean squared error. The resultant model had a correlation coefficient (r) of 0.71 (p < 0.001) with a root mean squared error (RMSE) of 49.8 ms between the predicted reaction time and true reaction time for each subject. Conclusion Non-invasive, non-disruptive monitoring could be used to track individual cognitive performance decrement due to sleep deficiency. This study examined the capability of combining the data from four physiological monitors that can be contained within a wrist worn device and a desk or helmet mounted camera. Utilizing 11 biometrics obtained from these monitors a stepwise regression model was developed that significantly correlates with PVT reaction time at both an individual and group level. Support This work was supported by the Military Operational Medicine Research Program.

Domain general processes moderate age-related performance differences on the mnemonic similarity task

ABSTRACTSeveral prominent domain general theories (e.g., processing speed and inhibitory function) have been developed to explain cognitive changes associated with aging. A bias to “pattern complete” in aging has also been suggested to account for some of the age-related changes in episodic memory. The current experiments test whether domain-general processes of cognitive aging moderate age-related performance decrements on the mnemonic similarity task, a task thought to rely on hippocampal pattern separation and completion. The study phase of the mnemonic similarity task, a memory task with old, new, and similar trials at recognition, was manipulated to assess the contribution of processing speed (Experiment 1 – different encoding times) and inhibitory function (Experiment 2 – item-level directed forgetting) to age-related performance differences in a sample of 100 healthy younger and older adults. Both experiments exhibited significant interactions between age group and encoding manipulation, replicating a decrement in performance in older adults, and indicating that processing speed and inhibitory function moderate this effect. Results suggest that age-related differences in performance on the mnemonic similarity task can at least partially be accounted for by experimental manipulations of domain general processes that also decline with age.

Impact of polysubstance use on social and non-affective cognitive performance among treatment-seeking individuals with alcohol use disorders

BackgroundIndividuals with alcohol use disorder (AUD) display deficits across a range of cognitive processes. Decrements in social cognition may be particularly important for interpersonal functioning and post-treatment adaptation. Although social cognitive deficits are associated with chronic use of numerous substances, the role of polysubstance use in AUD-associated deficits remains largely unaddressed. MethodsCommunity volunteers (n = 49; 22 men) and inpatient treatment-seekers with AUD were administered neurocognitive tasks indexing emotion processing and non-affective cognitive functioning. Tasks included an emotion discrimination task, a working memory task with affective stimuli, a general face processing (control) task, two measures of executive function, and two measures of visual spatial function. AUD subgroups included individuals with no recent (6-month) polysubstance use (AUD-Only; n = 22; 15 men), and those with at least weekly use (Poly-SU; n = 22; 18 men). ResultsPoly-SU individuals evinced disadvantaged performance relative to other groups on the emotion discrimination task [ps ≤ 0.001], affective working memory task [ps ≤ 0.050], and two executive function measures [ps ≤ 0.051]. No differences were observed for visual spatial functioning [ps ≥ 0.498] or general face processing [ps ≥ 0.190]. No performance differences between AUD-Only and community volunteers were noted. ConclusionsResults extend the emerging literature exploring emotion processing in AUD and add to the established literature regarding cognitive deficits in this population. The data suggest that among individuals with AUD, those with polysubstance use may be particularly vulnerable to deficits in decoding emotional face content. The current work highlights the need to incorporate more nuanced and careful considerations of polysubstance use in the design and analysis for future investigations of alcohol-associated deficits in emotion processing.

Self-Reported Sleep Need, Subjective Resilience, and Cognitive Performance Following Sleep Loss and Recovery Sleep.

Individuals vary in response to sleep loss: some individuals are "vulnerable" and demonstrate cognitive decrements following insufficient sleep, while others are "resistant" and maintain baseline cognitive capability. Physiological markers (e.g., genetic polymorphisms) have been identified that can predict relative vulnerability. However, a quick, cost-effective, and feasible subjective predictor tool has not been developed. The objective of the present study was to determine whether two factors-"subjective sleep need" and "subjective resilience"-predict cognitive performance following sleep deprivation. Twenty-seven healthy, sleep-satiated young adults participated. These individuals were screened for sleep disorders, comorbidities, and erratic sleep schedules. Prior to 40 hours of in-laboratory total sleep deprivation, participants were questioned on their subjective sleep need and completed a validated resilience scale. During and after sleep deprivation, participants completed a 5-minute psychomotor vigilance test every 2 hours. Both subjective resilience and subjective sleep need individually failed to predict performance during sleep loss. However, these two measures interacted to predict performance. Individuals with low resilience and low sleep need had poorer cognitive performance during sleep loss. However, in individuals with medium or high resilience, psychomotor vigilance test performance was not predicted by subjective sleep need. Higher resilience may be protective against sleep loss-related neurobehavioral impairments in the context of subjective sleep need. Following sleep loss (and recovery sleep), trait resilient individuals may outperform those with lower resiliency on real-world tasks that require continuous attention. Future studies should determine whether the present findings generalize to other, operationally relevant tasks and additional cognitive domains.

Anterior Cingulate Structure and Perfusion is Associated with Cerebrospinal Fluid Tau among Cognitively Normal Older Adult APOEɛ4 Carriers.

Evidence suggests the ɛ4 allele of the apolipoprotein E (APOE) gene may accelerate an age-related process of cortical thickening and cerebral blood flow (CBF) reduction in the anterior cingulate cortex (ACC). Although the neural basis of this association remains unclear, evidence suggests it might reflect early neurodegenerative processes. However, to date, associations between cerebrospinal fluid (CSF) biomarkers of neurodegeneration, such as CSF tau, and APOE-related alterations in ACC cortical thickness (CTH) and CBF have yet to be explored. The current study explored the interaction of CSF tau and APOE genotype (ɛ4+, ɛ4-) on FreeSurfer-derived CTH and arterial spin labeling MRI-measured resting CBF in the ACC (caudal ACC [cACC] and rostral ACC [rACC]) among a sample of 45 cognitively normal older adults. Secondary analyses also examined associations between APOE, CTH/CBF, and cognitive performance. In the cACC, higher CSF tau was associated with higher CTH and lower CBF in ɛ4+, whereas these relationships were not evident in ɛ4-. In the rACC, higher CSF tau was associated with higher CTH for both ɛ4+ and ɛ4-, and with lower CBF only in ɛ4+. Significant interactions of CSF tau and APOE on CTH/CBF were not observed in two posterior reference regions implicated in Alzheimer's disease. Secondary analyses revealed a negative relationship between cACC CTH and executive functioning in ɛ4+ and a positive relationship in ɛ4-. Findings suggest the presence of an ɛ4-related pattern of increased CTH and reduced CBF in the ACC that is associated with biomarkers of neurodegeneration and subtle decrements in cognition.

The cognitive and psychological effects of living with type 1 diabetes: a narrative review.

Across the lifespan, type 1 diabetes mellitus has a profound (neuro)psychological impact. In young people, type 1 diabetes can interfere with psychosocial development and hamper school performance. In adulthood, it can interfere with work life, relationships and parenting. A substantial minority of adults with type 1 diabetes experience coping difficulties and high diabetes‐related distress. In youth and adulthood, type 1 diabetes is related to mild cognitive decrements as well as affective disorders, such as depression and anxiety. There is limited literature available that explores the interaction between cognitive and psychological comorbidity and underlying mechanisms. The aims of the present narrative review were to summarize the current state of the literature regarding both cognitive and psychological comorbidities in type 1 diabetes across the lifespan, and to explore potential links between the two domains of interest to make suggestions for future research and clinical practice.

The neuroprotective effect and action mechanism of polyphenols in diabetes mellitus-related cognitive dysfunction

Diabetes mellitus (DM) is a complex and prevalent metabolic disorder worldwide. Strong evidence has emerged that DM is a risk factor for the accelerated rate of cognitive decline and the development of dementia. Though traditional pharmaceutical agents are efficient for the management of DM and DM-related cognitive decrement, long-term use of these drugs are along with undesired side effects. Therefore, tremendous studies have focused on the therapeutic benefits of natural compounds at present. Ample evidence exists to prove that polyphenols are capable to modulate diabetic neuropathy with minimal toxicity and adverse effects. To describe the benefits and mechanisms of polyphenols on DM-induced cognitive dysfunction. In this review, we introduce an updated overview of associations between DM and cognitive dysfunction. The risk factors as well as pathological and molecular mechanisms of DM-induced cognitive dysfunction are summarized. More importantly, many active polyphenols that possess preventive and therapeutic effects on DM-induced cognitive dysfunction and the potential signaling pathways involved in the action are highlighted. The therapeutic effects of polyphenols on DM-related cognitive dysfunction pave a novel way for the management of diabetic encephalopathy.

Functional equivalence of stem cell and stem cell-derived extracellular vesicle transplantation to repair the irradiated brain.

Cranial radiotherapy, although beneficial for the treatment of brain tumors, inevitably leads to normal tissue damage that can induce unintended neurocognitive complications that are progressive and debilitating. Ionizing radiation exposure has also been shown to compromise the structural integrity of mature neurons throughout the brain, an effect believed to be at least in part responsible for the deterioration of cognitive health. Past work has shown that cranially transplanted human neural stem cells (hNSCs) or their extracellular vesicles (EVs) afforded long‐term beneficial effects on many of these cognitive decrements. To provide additional insight into the potential neuroprotective mechanisms of cell‐based regenerative strategies, we have analyzed hippocampal neurons for changes in structural integrity and synaptic remodeling after unilateral and bilateral transplantation of hNSCs or EVs derived from those same cells. Interestingly, hNSCs and EVs similarly afforded protection to host neurons, ameliorating the impact of irradiation on dendritic complexity and spine density for neurons present in both the ipsilateral and contralateral hippocampi 1 month following irradiation and transplantation. These morphometric improvements were accompanied by increased levels of glial cell‐derived growth factor and significant attenuation of radiation‐induced increases in postsynaptic density protein 95 and activated microglia were found ipsi‐ and contra‐lateral to the transplantation sites of the irradiated hippocampus treated with hNSCs or hNSC‐derived EVs. These findings document potent far‐reaching neuroprotective effects mediated by grafted stem cells or EVs adjacent and distal to the site of transplantation and support their potential as therapeutic agents to counteract the adverse effects of cranial irradiation.

Neurocognitive impairment in type 2 diabetes mellitus.

There is emerging evidence that cognitive impairment could be a diabetes mellitus-related complication. It has been suggested that diabetic people are at increased risk of cognitive decline, since the metabolic and vascular disturbances of the disease affect brain function. Additionally, prolonged exposure to olther potential detrimental factors leads to irreversible cognitive decrements over time due to the aging process. Neurocognitive impairment signifies decreased performance in cognitive domains such as verbal and nonverbal memory, both immediate and delayed memory, executive function, attention, visuospatial and psychomotor performance, information processing speed, semantic knowledge, and language abilities. The aim of the present article is to review the existing literature on the issue of the neurocognitive decline in type 2 diabetes. A literature search of databases was performed, using as keywords "diabetes" and "cognitive impairment," and the reference list of papers so identified were examined, with only English language papers being used. Understanding and preventing diabetes-associated cognitive deficits remains a key priority for future research. It is important to ascertain whether interventions to delay diabetes onset or better control of established disease could prevent some of its adverse effects on cognitive skills.

Sleep inertia: current insights.

Sleep inertia, or the grogginess felt upon awakening, is associated with significant cognitive performance decrements that dissipate as time awake increases. This impairment in cognitive performance has been observed in both tightly controlled in-laboratory studies and in real-world scenarios. Further, these decrements in performance are exaggerated by prior sleep loss and the time of day in which a person awakens. This review will examine current insights into the causes of sleep inertia, factors that may positively or negatively influence the degree of sleep inertia, the consequences of sleep inertia both in the laboratory and in real-world settings, and lastly discuss potential countermeasures to lessen the impact of sleep inertia.

C-23 Impact of Social Support on Cognitive Vascular Risk Factors in Latino Older Adults

Abstract Objective Central Americans have a cardiovascular disease (CVD) health advantage, as they are half as likely to carry CVD as European Americans, despite having an equivalent degree of vascular risk factors (VRFs). We examined the impact of social support on this paradox and the relationship to cognitive decrements among Costa Rican older adults. Methods We identified predictors of the CVD health advantage (VRFs in the absence of CVD: Heart Attack, MI, Stroke). Hypertension (HTN) and CVD were coded as present or absent based on medical history. Of 315 participants, 146 (46%) had HTN but no CVD, 59 (19%) had CVD, and 110 had neither HTN nor CVD. To estimate ROC curves, we applied canonical discriminant analysis to item groups based on the discipline cluster. The discriminant analysis identified items that maximally differentiated the diagnostic groups in a step-wise fashion. Results Social support and social engagement were stronger predictors of the health advantage than subjective memory complaints. Social Support was a reliable indicator of CVD health advantage (accuracy = 93%, sensitivity = 93%, specificity = 89%). Social Engagement was a reliable discriminator of diagnostic groups (accuracy = 84%, sensitivity = 88%, specificity =75%) versus subjective memory complaints (accuracy = 79%, sensitivity of 82%, specificity of 74%). Conclusion Our exploratory analyses suggest that social support is an important predictor of living with VRFs but not developing CVD. Current studies are underway to examine the contribution of these risk factors to the development of dementia and cognitive impairment to maximize cost-effective interventions.

Honesty in reporting suicidal ideations and behaviors in Alzheimer’s disease, mild cognitive impairment, and dementias

<p class="abstract"><strong>Background:</strong> Detection of patients’ suicidal ideations and behaviors (SIB) is critical to patient safety. It is important to consider the needs, abilities and propensity for honesty in reporting SIB in populations with compromised cognitive abilities. We surveyed patients with compromised cognitive abilities to determine if they feel they would report SIB and the conditions under which they would be honest in reporting SIB?</p><p class="abstract"><strong>Methods:</strong> Patients reporting diagnoses such as Alzheimer’s disease (AD), mild cognitive impairment (MCI) or other dementias completed online surveys. Participants were asked their likelihood for honesty, preferences and comfort when answering questions on SIB in-person and using electronic self-report.</p><p class="abstract"><strong>Results:</strong> 73 patients with AD, MCI or other dementias, 95% reported they were likely to report SIB honestly electronically and 92% would be honest with a health care provider (HCP). However, 96% would be honest in-person with an HCP they knew but less than 88% said they would be honest if they didn’t know the HCP.</p><p class="abstract"><strong>Conclusions: </strong>These data suggest that patients with cognitive conditions may be more likely to report SIB truthfully using electronic self-report than a clinical face to face interview but that either form of reporting is an effective methodology for obtaining honest responses about SIB. Taking the FDA guidance on suicidality and the potential for cognitive decrements in this population, multiple tools for assessing depression and SIB should be implemented when treating or working this population.</p>

Olfactory Dysfunction Mediates Adiposity in Cognitive Impairment of Type 2 Diabetes: Insights From Clinical and Functional Neuroimaging Studies.

Large numbers of people with type 2 diabetes are obese. However, changes in cognition and related brain function in obese people with diabetes have not been characterized. Here, we investigated cognition, olfactory function, and odor-induced brain alterations in these patients and therapeutic effects of glucagon-like peptide 1 receptor agonists (GLP-1Ras) on their psychological behavior and olfactory networks. Cognitive, olfactory, and odor-induced brain activation assessments were administered to 35 obese and 35 nonobese people with type 2 diabetes and 35 control subjects matched for age, sex, and education. Among them, 20 obese individuals with diabetes with inadequate glycemic control and metformin monotherapy received GLP-1Ra treatment for 3 months and were reassessed for metabolic, cognitive, olfactory, and neuroimaging changes. Obese subjects with diabetes demonstrated lower general cognition and olfactory threshold scores, decreased left hippocampal activation, and disrupted seed-based functional connectivity with right insula compared with nonobese subjects with diabetes. Negative associations were found between adiposity and episodic memory and between fasting insulin and processing speed test time in diabetes. Mediation analyses showed that olfactory function and left hippocampus activation mediated these correlations. With 3-month GLP-1Ra treatment, obese subjects with diabetes exhibited improved Montreal Cognitive Assessment (MoCA) score, olfactory test total score, and enhanced odor-induced right parahippocampus activation. Obese subjects with type 2 diabetes showed impaired cognition and dysfunctional olfaction and brain networks, the latter of which mediated adiposity in cognitive impairment of diabetes. GLP-1Ras ameliorated cognitive and olfactory abnormalities in obese subjects with diabetes, providing new perspectives for early diagnosis and therapeutic approaches for cognitive decrements in these patients.

A Review of Cognitive Outcomes Across Movement Disorder Patients Undergoing Deep Brain Stimulation.

Introduction: Although the benefit in motor symptoms for well-selected patients with deep brain stimulation (DBS) has been established, cognitive declines associated with DBS can produce suboptimal clinical responses. Small decrements in cognition can lead to profound effects on quality of life. The growth of indications, the expansion of surgical targets, the increasing complexity of devices, and recent changes in stimulation paradigms have all collectively drawn attention to the need for re-evaluation of DBS related cognitive outcomes.Methods: To address the impact of cognitive changes following DBS, we performed a literature review using PubMed. We searched for articles focused on DBS and cognition. We extracted information about the disease, target, number of patients, assessment of time points, cognitive battery, and clinical outcomes. Diseases included were dystonia, Tourette syndrome (TS), essential tremor (ET), and Parkinson's disease (PD).Results: DBS was associated with mild cognitive issues even when rigorous patient selection was employed. Dystonia studies reported stable or improved cognitive scores, however one study using reliable change indices indicated decrements in sustained attention. Additionally, DBS outcomes were convoluted with changes in medication dose, alleviation of motor symptoms, and learning effects. In the largest, prospective TS study, an improvement in attentional skills was noted, whereas smaller studies reported variable declines across several cognitive domains. Although, most studies reported stable cognitive outcomes. ET studies largely demonstrated deficits in verbal fluency, which had variable responses depending on stimulation setting. Recently, studies have focused beyond the ventral intermediate nucleus, including the post-subthalamic area and zona incerta. For PD, the cognitive results were heterogeneous, although deficits in verbal fluency were consistent and related to the micro-lesion effect.Conclusion: Post-DBS cognitive issues can impact both motor and quality of life outcomes. The underlying pathophysiology of cognitive changes post-DBS and the identification of pathways underpinning declines will require further investigation. Future studies should employ careful methodological designs. Patient specific analyses will be helpful to differentiate the effects of medications, DBS and the underlying disease state, including disease progression. Disease progression is often an underappreciated factor that is important to post-DBS cognitive issues.

SAT-261 Prospective Study of the Association between Early Adrenarche and Cognitive Function in Children with Cushing Disease

Background: Previously, we reported a decline in cognitive scores of children with endogenous Cushing syndrome (CS); however, the generalizability of the findings is limited due to the small sample size. The present study investigated the relationship between change in cognitive scores prior to and one-year post transsphenoidal surgery, with age at initial presentation, duration of illness, and history of premature adrenarche (PA) as covariates. Both cortisol and adrenal androgens have key roles in the organizational and the maturational changes in brain structure and function during adolescence. Method: Prospective study of 41 children (17 females; 12 ±3 yr.) diagnosed with Cushing’s disease (CD), who completed diverse sets of cognitive measures prior to and one-year post-remission: (Wechsler Intelligence Scale for Children (WISC) or Wechsler Adult Intelligence Scale of Intelligence (WASI), Woodcock Johnson Psychoeducational Battery, California Verbal Learning, and Trail making tests. Linear regression of delta change in IQ test scores (from baseline to 1-year remission) with covariates of age, duration of illness, and history of premature adrenarche was used to analyze the data. Results: At baseline, children with CD had average to above average intelligence. Change in scores from baseline to 1-year remission was significant for performance IQ (PIQ), verbal IQ (VIQ), full IQ (FIQ), subsets: information, similarities, arithmetic, vocabulary, coding, and block design (p<0.01). Younger age at baseline with a history of PA was associated with a greater decrement in scores PIQ VIQ FIQ, coding, and block design(p<0.01). At baseline, serum DHEAS levels were discordant with pubertal stage in subjects <14yrs age; this discrepancy resolved at 1-yr remission. Conclusion: Younger age at baseline was a predictor of decrement in all summary IQ measures and some subset measures (picture completion, coding, & block design, arithmetic), (p < 0.01). Older age at presentation was associated with less of a decline in cognitive function measures, which suggests that after a return to eucortisolemia, the response of older adolescents is more similar to adult CD patients. At baseline, younger children with CD had DHEAS levels discordant with pubertal stage and were more likely to experience cognitive decrement after remission, suggesting that timing of adrenarche is an important moderator of cognitive function in children with CD.

Irregular structural networks of gray matter in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) induces dementia and cognitive decrements indicating the impairment of the central nervous system. While there is evidence showing abnormalities in white-matter structural networks in T2DM, the topological features of gray matter are still unknown. The study enrolled 30 right-handed T2DM patients and 20 healthy control subjects with matched age, gender, handedness, and education. Graph theoretical analysis of magnetic resonance imaging on gray matter volume was conducted to explore large-scale structural networks of brain. Although retaining small-worldness characteristics, the structural networks of grey matter in the T2DM group exhibited an increased clustering coefficient, prolonged characteristic path, decreased global efficiency, and more vulnerability to random failures or targeted attacks compared with controls. Additionally, the degree of structural networks in both T2DM and control groups was distributed exponentially in truncated power law. Our findings suggest that T2DM disturbed the overall topological features of gray matter networks, which provides a novel insight into the neurobiological mechanisms accounting for the cognitive impairment of T2DM patients.

A Multifactor Approach to Mild Cognitive Impairment.

Mild cognitive impairment (MCI) represents an intermediate stage between normal cognition and dementia. Individuals with MCI are at increased risk of conversion to dementia, and the rate of progression of MCI to dementia is dependent on age, gender, and education. MCI may be diagnosed using neuropsychological criteria using cut-offs representing decrements in cognition, or using criteria to assess for a decline in functional status. The ability to determine the status of dementia-related biomarkers has allowed for better staging and prognostication in different forms of MCI. MCI is now recognized as a significant target stage for future therapies. These future therapies aim to reduce the rate of conversion of individuals with MCI to dementia. In this article, we review different conceptions of MCI, the diagnosis and prognostication of MCI, and presently available management approaches for this condition.

Investigating the role of expectancy in caffeine withdrawal using the balanced placebo design.

This study investigated psychological influences on drug withdrawal symptomatology using a caffeine-based model. Using the 2×2 balanced placebo design caffeine dose (given caffeinated vs decaffeinated coffee) was crossed with dose expectancy (told caffeine vs. decaf) among 87 (16-hr abstinent) regular coffee consumers in a 2-day study. There were effects of expectancy and pharmacology that differed depending on the measure. Those told decaf reported greater caffeine cravings than those told caffeine 45min and 8hr postmanipulation. There were no expectancy effects on withdrawal symptoms or cognitive performance. There were pharmacological effects on all measures. Those given decaf reported greater withdrawal symptoms and showed poorer cognitive performance 45min and 8hr postmanipulation, with effects for headache and flu-like symptoms first emerging 8hr postmanipulation (i.e., 24hr abstinence in given decaf conditions). Caffeine readministration alleviated all withdrawal symptoms and cognitive decrements within 45min. No drug by expectancy interactions were observed. These findings confirm a strong pharmacological basis for caffeine withdrawal and an important role of cognition in drug craving. Future research should investigate the role of expectancy in drug withdrawal and craving and the potential use of expectancy manipulations in symptom prevention and management.

Compensatory Hippocampal Connectivity in Young Adults With Early-Stage Type 2 Diabetes.

Middle-aged to elderly patients with type 2 diabetes mellitus (T2DM) exhibit reduced functional connectivity and brain atrophy underlying cognitive decrements; however, little is known about brain abnormalities in young patients. To detect brain anatomical and functional changes in young patients with T2DM during the early disease stage. Case-control study. Tertiary referral hospital. Thirty-five young patients with T2DM (<40 years of age) with no detectable microangiopathy and 32 nondiabetic control subjects. None. Subjects underwent neuropsychological assessments and structural and resting-state functional MRI. Both voxel-based morphometry and resting-state functional connectivity analyses were performed. No significant differences in brain volume were observed between the patients with T2DM and the controls after controlling for age, sex, education, and body mass index. Compared with the controls, the patients showed greater connectivity of the left hippocampus with the left inferior frontal gyrus and the left inferior parietal lobule. Moreover, the enhanced functional connectivity of left hippocampus with the left inferior frontal gyrus significantly correlated with disease severity (urinary albumin-to-creatinine ratio) (r = 0.613, P < 0.001) and executive function (completion time of Stroop Color and Word Test) (r = -0.461, P = 0.005) after false discovery rate correction. Our findings suggest an adaptive compensation of brain function to counteract the insidious cognitive decrements during the early stage of T2DM. Additionally, the functional alterations occurring before changes in brain structure and peripheral microangiopathy might serve as early biomarkers related to cognitive decrements.