The Impact of Awareness of and Concern About Memory Performance on the Prediction of Progression From Mild Cognitive Impairment to Alzheimer Disease Dementia.

OBJECTIVE: To investigate the relationship of awareness of and concern about memory performance to progression from mild cognitive impairment (MCI) to Alzheimer disease (AD) dementia. METHODS: Participants (n = 33) had a diagnosis of MCI at baseline and a diagnosis of MCI or AD dementia at follow-up. Participants were categorized as "Stable-MCI" if they retained an MCI diagnosis at follow-up (mean follow-up = 18.0 months) or "Progressor-MCI" if they were diagnosed with AD dementia at follow-up (mean follow-up = 21.6 months). Awareness was measured using the residual from regressing a participant's objective memory score onto their subjective complaint score (i.e., residual<0 indicates overestimation of performance). Concern was assessed using a questionnaire examining the degree of concern when forgetting. Logistic regression was used to determine whether the presence of these syndromes could predict future diagnosis of AD dementia, and repeated measures analysis of covariance tests were used to examine longitudinal patterns of these syndromes. RESULTS: Baseline anosognosia was apparent in the Progressor-MCI group, whereas participants in the Stable-MCI group demonstrated relative awareness of their memory performance. Baseline awareness scores successfully predicted whether an individual would progress to AD-dementia. Neither group showed change in awareness of performance over time. Neither group showed differences in concern about memory performance at baseline or change in concern about performance over time. CONCLUSION: These data suggest that anosognosia may appear prior to the onset of AD dementia, while anosodiaphoria likely does not appear until later in the AD continuum. Additionally, neither group showed significant changes in awareness or concern over time, suggesting that change in these variables may happen over longer periods.

Orbitofrontal cortex encodes memories within value-based schemas and represents contexts that guide memory retrieval.

There are a substantial number of studies showing that the orbitofrontal cortex links events to reward values, whereas the hippocampus links events to the context in which they occur. Here we asked how the orbitofrontal cortex contributes to memory where context determines the reward values associated with events. After rats learned object-reward associations that differed depending on the spatial context in which the objects were presented, neuronal ensembles in orbitofrontal cortex represented distinct value-based schemas, each composed of a systematic organization of the representations of objects in the contexts and positions where they were associated with reward or nonreward. Orbitofrontal ensembles also represent the different spatial contexts that define the mappings of stimuli to actions that lead to reward or nonreward. These findings, combined with observations on complementary memory representation within the hippocampus, suggest mechanisms through which prefrontal cortex and the hippocampus interact in support of context-guided memory.

Recent contributions to the field of subjective cognitive decline in aging: A literature review.

Subjective cognitive decline (SCD) is defined as self-experienced, persistent concerns of decline in cognitive capacity in the context of normal performance on objective cognitive measures. Although SCD was initially thought to represent the "worried well," these concerns can be linked to subtle brain changes prior to changes in objective cognitive performance and, therefore, in some individuals, SCD may represent the early stages of an underlying neurodegenerative disease process (e.g., Alzheimer's disease). The field of SCD research has expanded rapidly over the years, and this review aims to provide an update on new advances in, and contributions to, the field of SCD in key areas and themes identified by researchers in this field as particularly important and impactful. First, we highlight recent studies examining sociodemographic and genetic risk factors for SCD, including explorations of SCD across racial and ethnic minoritized groups, and examinations of sex and gender considerations. Next, we review new findings on relationships between SCD and in vivo markers of pathophysiology, utilizing neuroimaging and biofluid data, as well as associations between SCD and objective cognitive tests and neuropsychiatric measures. Finally, we summarize recent work on interventions for SCD and areas of future growth in the field of SCD.

Longitudinal Trajectories of Participant- and Study Partner-Rated Cognitive Decline, in Relation to Alzheimer's Disease Biomarkers and Mood Symptoms.

Whereas discrepancies between participant- and study partner-reported cognitive concerns on the Alzheimer's disease (AD) continuum have been observed, more needs to be known regarding the longitudinal trajectories of participant- vs. study partner-reported concerns, particularly their relationship to AD biomarkers and mood symptomology. Additionally, it is unclear whether years of in-clinic data collection are needed to observe relationships with AD biomarkers, or whether more frequent, remote assessments over shorter periods of time would suffice. This study primarily sought to examine the relationships between longitudinal trajectories of participant- and study partner-rated cognitive decline and baseline biomarker levels [i.e., amyloid and tau positron emission tomography (PET)], in addition to how mood symptomatology may alter these trajectories of concerns over a 2-year period. Baseline mood was associated with longitudinal participant-rated concerns, such that participants with elevated depression and anxiety scores at baseline had decreasing concerns about cognitive decline over time (fixed estimate = -0.17, 95% CI [-0.29 to -0.05], t = -2.75, df = 457, adj. p = 0.012). A significant interaction between baseline amyloid (fixed estimate = 4.07, 95% CI [1.13-7.01], t = 2.72, df = 353, adj. p = 0.026) and tau (fixed estimate = 3.50, 95% CI [0.95-6.06], t = 2.70, df = 331, adj. p = 0.030) levels was associated with increasing study partner concerns, but not participant concerns, over time. The interaction between amyloid and study partner concerns remained significant when utilizing only the first year of concern-related data collection. Overall, these results suggest that frequent, remote assessment of study partner-reported concerns may offer additional insight into the AD clinical spectrum, as study partners appear to more accurately update their concerns over time with regard to pathology, with these concerns less influenced by participants' mood symptomatology.

Workload Monitoring in Team Sports: Using Elite Cricket as an Example.

Workload monitoring is used to assess athlete preparedness to ensure that they are optimally prepared for competition. Although many workload studies have been done, most are delimited to individual sport athletes and endurance athletes. There is also controversy regarding which measures and in what combinations they should be used. There is a paucity of literature on workload monitoring in team sports such as cricket. Cricket is an interesting and complex sport which has dimensions of many other sports (team and individual) and was the focus of this broad, narrative review. The review highlights the unique demands of the sport and why consideration of the sport in question is important. It further identifies that most of the workload research has been done on fast bowlers with debate surrounding optimal workloads. It calls for research in specific areas and importantly on other player positions considering their unique demands and identifies what can be used currently by practitioners in the field.

Anosognosia for memory deficits in mild cognitive impairment: Insight into the neural mechanism using functional and molecular imaging.

Anosognosia, or loss of insight of memory deficits, is a common and striking symptom in Alzheimer's disease (AD). Previous findings in AD dementia patients suggest that anosognosia is due to both functional metabolic changes within cortical midline structures involved in self-referential processes, as well as functional disconnection between these regions. The present study aims to extend these findings by investigating the neural correlates of anosognosia in the prodromal stage of AD. Here, we used regional brain metabolism (resting state 18-F fluorodeoxyglucose positron emission tomography (FDG-PET)) to unravel the metabolic correlates of anosognosia in subjects with amnestic mild cognitive impairment (aMCI) and subsequently resting state functional magnetic resonance imaging (rs-fMRI) to investigate the intrinsic connectivity disruption between brain regions. Thirty-one subjects (mean age: 74.1; Clinical Dementia Rating (CDR) global score: 0.5) with aMCI, and 251 cognitively normal (CN) older adults (mean age: 73.3; CDR: 0) were included as a reference group for behavioral and FDG data. An anosognosia index was obtained by calculating a discrepancy score between subjective and objective memory scores. All subjects underwent FDG-PET for glucose metabolism measurement, and aMCI subjects underwent additional rs-fMRI for intrinsic connectivity measurement. Voxel-wise correlations between anosognosia and neuroimaging data were conducted in the aMCI subjects. Subjects with aMCI had significantly decreased memory awareness as compared to the CN older adults. Greater anosognosia in aMCI subjects was associated with reduced glucose metabolism in the posterior cingulate (PCC) cortices and hippocampus. Intrinsic connectivity analyses revealed a significant association between anosognosia and attenuated functional connectivity between the PCC seed region and orbitofrontal cortex (OFC) as well as bilateral inferior parietal lobes (IPL). These findings provide further evidence that implicates cortical midline structures and hippocampus in the awareness of memory deficits. Investigating neuroimaging changes that co-vary with memory awareness may improve our ability to identify the cause of anosognosia and ultimately increase our chances for its treatment.

Hippocampal hypometabolism in older adults with memory complaints and increased amyloid burden.

OBJECTIVE: To identify the functional and pathologic correlates underlying subjective memory complaints (SMCs) in cognitively normal older adults. METHODS: Two hundred fifty-one older adults underwent resting-state fluorodeoxyglucose (FDG)-PET and Pittsburg compound B-PET ß-amyloid (Aß) imaging and filled out a questionnaire regarding SMCs. Participants were classified into 2 groups based on their Aß burden. Age-adjusted voxel-wise correlations were used to examine SMCs, amyloid status (Aß+ vs Aß-), and the interaction between SMCs and Aß status as predictors of metabolism. Region-of-interest (ROI) analyses were performed to confirm the whole-brain analyses and to test for additional covariates. RESULTS: Greater SMCs correlated with decreased FDG metabolism in the bilateral precuneus, bilateral inferior parietal lobes, right inferior temporal lobe, right medial frontal gyrus, and right orbitofrontal gyrus. A significant interaction effect between SMCs and amyloid burden was found such that Aß+ individuals with increased complaints had decreased FDG metabolism in the bilateral medial temporal lobes. ROI analyses confirmed the voxel-wise analyses result in that decreased precuneus metabolism was associated with greater SMCs regardless of Aß status, age, or thickness, whereas the relationship between hippocampal metabolism and SMCs was a function of Aß, even after adjustment for age, hippocampal volume, or depressive symptoms. CONCLUSIONS: These data show the relevant role of posterior and anterior midline regions in SMCs in older individuals. Decreased hippocampal metabolism may be a specific marker of subclinical changes in cognition due to amyloid pathology. However, longitudinal studies are needed to determine whether our findings foreshadow clinical decline.

The Apathy Evaluation Scale: A Comparison of Subject, Informant, and Clinician Report in Cognitively Normal Elderly and Mild Cognitive Impairment.

BACKGROUND: Apathy is a common neuropsychiatric symptom in Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI). Detecting apathy accurately may facilitate earlier diagnosis of AD. The Apathy Evaluation Scale (AES) is a promising tool for measurement of apathy in prodromal and possibly preclinical AD. OBJECTIVE: To compare the three AES sub-scales - subject-reported (AES-S), informant-reported (AES-I), and clinician-reported (AES-C) - over time in individuals at risk for AD due to MCI and advanced age (cognitively normal [CN] elderly). METHODS: Mixed effects longitudinal models were used to assess predictors of score for each AES sub-scale. Cox proportional hazards models were used to assess which AES sub-scales predict progression from MCI to AD dementia. RESULTS: Fifty-seven MCI and 18 CN subjects (ages 53-86) were followed for 1.4 ± 1.2 years and 0.7 ± 0.7 years, respectively. Across the three mixed effects longitudinal models, the common findings were associations between greater apathy and greater years in study, a baseline diagnosis of MCI (compared to CN), and male gender. CN elderly self-reported greater apathy compared to that reported by informants and clinicians, while individuals with MCI under-reported their apathy compared to informants and clinicians. Of the three sub-scales, the AES-C best predicted transition from MCI to AD dementia. CONCLUSION: In a sample of CN elderly and elderly with MCI, apathy increased over time, particularly in men and those with MCI. AES-S scores may be more sensitive than AES-I and AES-C scores in CN elderly, but less reliable if subjects have MCI. Moreover, the AES-C sub-scale predicted progression from MCI to AD dementia.

Neuropsychiatric Symptoms and Functional Connectivity in Mild Cognitive Impairment.

BACKGROUND: Neuropsychiatric symptoms (NPS), such as apathy and depression, commonly accompany cognitive and functional decline in early Alzheimer's disease (AD). Prior studies have shown associations between affective NPS and neurodegeneration of medial frontal and inferior temporal regions in mild cognitive impairment (MCI) and AD dementia. OBJECTIVE: To investigate the association between functional connectivity in four brain networks and NPS in elderly with MCI. METHODS: NPS were assessed using the Neuropsychiatric Inventory in 42 subjects with MCI. Resting-state functional connectivity in four networks (default mode network, fronto-parietal control network (FPCN), dorsal attention network, and ventral attention network) was assessed using seed-based magnetic resonance imaging. Factor analysis was used to identify two factors of NPS: Affective and Hyperactivity. Linear regression models were utilized with the neuropsychiatric factors as the dependent variable and the four networks as the predictors of interest. Covariates included age, gender, premorbid intelligence, processing speed, memory, head movement, and signal-to-noise ratio. These analyses were repeated with the individual items of the affective factor, using the same predictors. RESULTS: There was a significant association between greater Affective factor symptoms and reduced FPCN connectivity (p = 0.03). There was no association between the Hyperactivity factor and any of the networks. Secondary analyses revealed an association between greater apathy and reduced FPCN connectivity (p = 0.005), but none in other networks. CONCLUSIONS: Decreased connectivity in the FPCN may be associated with greater affective symptoms, particularly apathy, early in AD. These findings extend prior studies, using different functional imaging modalities in individuals with greater disease severity.