To identify novel associations between modifiable physical and health variables, Alzheimer’s disease (AD) biomarkers, and cognitive function in a cohort of older adults with Mild Cognitive Impairment (MCI).

Metrics of cardiometabolic risk, stress, inflammation, neurotrophic/growth factors, AD, and cognition were assessed in 154 MCI participants (Mean age = 74.1 years) from the Alzheimer’s Disease Neuroimaging Initiative. Partial Least Squares analysis was employed to examine associations among these physiological variables and cognition.

Latent variable 1 revealed a unique combination of AD biomarkers, neurotrophic/growth factors, education, and stress that were significantly associated with specific domains of cognitive function, including episodic memory, executive function, processing speed, and language, representing 45.2% of the cross-block covariance in the data. Age, body mass index, and metrics tapping basic attention or premorbid IQ were not significant.

Our data-driven analysis highlights the significant relationships between metrics associated with AD pathology, neuroprotection, and neuroplasticity, primarily with tasks tapping episodic memory, executive function, processing speed, and verbal fluency rather than more basic tasks that do not require mental manipulation (basic attention and vocabulary). These data also indicate that biological metrics are more strongly associated with episodic memory, executive function, and processing speed than chronological age in older adults with MCI.

While emotional responses experienced in-the-moment appear to remain intact in Parkinson’s disease (PD), no study has tested whether this extends to the prediction of future emotional responses. The present study aimed to provide the first assessment of affective forecasting capacity in this cohort.

A positively and negatively valenced affective forecasting task and broader clinical battery were completed by a PD group (ns = 28 and 37, respectively) and a demographically matched neurotypical control group (ns = 38 and 39, respectively).

No group differences emerged on the two tasks, with the two groups underestimating their level of happiness and overestimating their level of negative affect to a similar degree. Affective forecasting error scores were unrelated to clinical characteristics.

Given that affective forecasting relies on self-projection into the future, a skill shown to often be disrupted in this cohort, impairments were expected. However, this study provides initial evidence that this may not be the case. These findings are potentially important given that how we think about and envisage the future affectively is a major determinant of goal-directed behavior. Further work is now needed to establish whether these findings are robust and generalize to other types of affective stimuli.

The aim of this study was to model the relationships among white matter hyperintensities (WMHs), depressive symptoms, and cognitive function and to examine the mediating effect of depressive symptoms on the relationship between WMHs and cognitive impairment.

We performed structural equation modeling using cross-sectional data from 1158 patients from the Clinical Research for Dementia of South Korea (CREDOS) registry who were diagnosed with mild-to-moderate dementia. Periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs) were obtained separately on the protocol of magnetic resonance imaging (MRI). Depression and cognitive function were assessed using the Korean Form of the Geriatric Depression Scale (KGDS) and the Seoul Neuropsychological Screening Battery (SNSB), respectively.

The model that best reflected the relationships among the variables was the model in which DWMHs affected cognitive function directly and indirectly through the depressive symptoms; on the other hand, PWMHs only directly affected cognitive function.

This study presents the mediation model including the developmental pathway from DWMHs to cognitive impairment through depressive symptoms and suggests that the two types of WMHs may affect cognitive impairment through different pathways.

The Weigl Colour-Form Sorting Test is a brief, widely used test of executive function. So far, it is unknown whether this test is specific to frontal lobe damage. Our aim was to investigate Weigl performance in patients with focal, unilateral, left or right, frontal, or non-frontal lesions.

We retrospectively analysed data from patients with focal, unilateral, left or right, frontal (n = 37), or non-frontal (n = 46) lesions who had completed the Weigl. Pass/failure (two correct solutions/less than two correct solutions) and errors were analysed.

A greater proportion of frontal patients failed the Weigl than non-frontal patients, which was highly significant (p < 0.001). In patients who failed the test, a significantly greater proportion of frontal patients provided the same solution twice. No significant differences in Weigl performance were found between patients with left versus right hemisphere lesions or left versus right frontal lesions. There was no significant correlation between performance on the Weigl and tests tapping fluid intelligence.

The Weigl is specific to frontal lobe lesions and not underpinned by fluid intelligence. Both pass/failure on this test and error types are informative. Hence, the Weigl is suitable for assessing frontal lobe dysfunction.

To compare longitudinal verbal fluency performance among Latinx Spanish speakers who develop Alzheimer’s disease to those who do not develop dementia in absolute number of words produced on each task and their ratio to combine both scores.

Participants included 833 Latinx Spanish-speaking older adults from a community-based prospective cohort in Manhattan. We performed growth curve modeling to investigate the trajectories of letter and semantic fluency, and their ratio (i.e., ‘semantic index’), between individuals who developed Alzheimer’s disease and those who did not (i.e., controls). The semantic index quantifies the proportion of words generated for semantic fluency in relation to the total verbal fluency performance.

Letter fluency performance did not decline in controls; we observed a linear decline in those who developed Alzheimer’s disease. Semantic fluency declined in both groups and showed an increased rate of change over time in the incident Alzheimer’s disease group; in comparison, the control group had a linear and slower decline. There were no group differences in the longitudinal trajectory (intercept and slope) of the semantic index.

A decline in letter fluency and a more rapid and accelerating decline over time in semantic fluency distinguished people who developed Alzheimer’s disease from controls. Using the semantic index was not a superior marker of incident Alzheimer’s disease compared to examining the two fluency scores individually. Results suggest the differential decline in verbal fluency tasks, when evaluated appropriately, may be useful for early identification of Alzheimer’s disease in Latinx Spanish speakers, a historically understudied population.

“Ecological validity” (EV) is classically defined as test’s ability to predict real-world functioning, either alone or together with test’s similarity to real-world tasks. In neuropsychological literature on assessment of executive functions (EF), EV is conceptualized inconsistently, leading to misconceptions about the utility of tests. The goal of this systematic review was to examine how EV is conceptualized in studies of EF tests described as ecologically valid.

MEDLINE and PsychINFO Databases were searched. PRISMA guidelines were observed. After applying inclusion and exclusion criteria, this search yielded 90 articles. Deductive content analysis was employed to determine how the term EV was used.

About 1/3 of the studies conceptualized EV as the test’s ability to predict functional outcomes, 1/3 as both the ability to predict functional outcome and similarity to real-world tasks, and 1/3 were either unclear about the meaning of the term or relied on notions unrelated to classical definitions (e.g., similarity to real-world tasks alone, association with other tests, or the ability to discriminate between populations).

Conceptualizations of the term EV in literature on EF assessment vary grossly, subsuming the notions of criterion, construct, and face validity, as well as sensitivity/specificity. Such inconsistency makes it difficult to interpret clinical utility of tests that are described as ecologically valid. We call on the field to require that, at minimum, the term EV be clearly defined in all publications, or replaced with more concrete terminology (e.g., criterion validity).

Functional neurological symptom disorder (FNSD) is a neuropsychiatric condition characterized by signs/symptoms associated with brain network dysfunction. FNSDs are common and are associated with high healthcare costs. FNSDs are relevant to neuropsychologists, as they frequently present with chronic neuropsychiatric symptoms, subjective cognitive concerns, and/or low neuropsychological test scores, with associated disability and reduced quality of life. However, neuropsychologists in some settings are not involved in care of patients with FNSDs. This review summarizes relevant FNSD literature with a focus on the role of neuropsychologists.

A brief review of the literature is provided with respect to epidemiology, public health impact, symptomatology, pathophysiology, and treatment.

Two primary areas of focus for this review are the following: (1) increasing neuropsychologists’ training in FNSDs, and (2) increasing neuropsychologists’ role in assessment and treatment of FNSD patients.

Patients with FNSD would benefit from increased involvement of neuropsychologists in their care.

Maintaining attention underlies many aspects of cognition and becomes compromised early in neurodegenerative diseases like Alzheimer’s disease (AD). The consistency of maintaining attention can be measured with reaction time (RT) variability. Previous work has focused on measuring such fluctuations during in-clinic testing, but recent developments in remote, smartphone-based cognitive assessments can allow one to test if these fluctuations in attention are evident in naturalistic settings and if they are sensitive to traditional clinical and cognitive markers of AD.

Three hundred and seventy older adults (aged 75.8 +/− 5.8 years) completed a week of remote daily testing on the Ambulatory Research in Cognition (ARC) smartphone platform and also completed clinical, genetic, and conventional in-clinic cognitive assessments. RT variability was assessed in a brief (20-40 seconds) processing speed task using two different measures of variability, the Coefficient of Variation (CoV) and the Root Mean Squared Successive Difference (RMSSD) of RTs on correct trials.

Symptomatic participants showed greater variability compared to cognitively normal participants. When restricted to cognitively normal participants, APOE ε4 carriers exhibited greater variability than noncarriers. Both CoV and RMSSD showed significant, and similar, correlations with several in-clinic cognitive composites. Finally, both RT variability measures significantly mediated the relationship between APOE ε4 status and several in-clinic cognition composites.

Attentional fluctuations over 20–40 seconds assessed in daily life, are sensitive to clinical status and genetic risk for AD. RT variability appears to be an important predictor of cognitive deficits during the preclinical disease stage.

Evidence-based diagnostic methods have clinical and research applications in neuropsychology. A flexible Bayesian model was developed to yield diagnostic posttest probabilities from a single person’s neuropsychological score profile by utilizing sample descriptive statistics of the test battery across diagnostic populations of interest.

Three studies examined the model’s performance. One simulation examined estimation accuracy of true z-scores. A diagnostic accuracy simulation utilized descriptive statistics from two popular neuropsychological tests, the Wechsler Adult Intelligence Scale–IV (WAIS-IV) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The final simulation examined posterior predictive accuracy of scores to those reported in the WAIS manual.

The model produced minimally biased z-score estimates (root mean square errors: .02–.18) with appropriate credible intervals (95% credible interval empirical coverage rates: .94–1.00). The model correctly classified 80.87% of simulated normal, mild cognitive impairment, and Alzheimer’s disease cases using a four subtest WAIS-IV and the RBANS compared to accuracies of 60.67–65.60% from alternative methods. The posterior predictions of raw scores closely aligned to percentile estimates published in the WAIS-IV manual.

This model permits estimation of posttest probabilities for various combinations of neuropsychological tests across any number of clinical populations with the principal limitation being the accessibility of applicable reference samples. The model produced minimally biased estimates of true z-scores, high diagnostic classification rates, and accurate predictions of multiple reported percentiles while using only simple descriptive statistics from reference samples. Future nonsimulation research on clinical data is needed to fully explore the utility of such diagnostic prediction models.

Self- and informant-ratings of functional abilities are used to diagnose mild cognitive impairment (MCI) and are commonly measured in clinical trials. Ratings are assumed to be accurate, yet they are subject to biases. Biases in self-ratings have been found in individuals with dementia who are older and more depressed and in caregivers with higher distress, burden, and education. This study aimed to extend prior findings using an objective approach to identify determinants of bias in ratings.

Participants were 118 individuals with MCI and their informants. Three discrepancy variables were generated including the discrepancies between (1) self- and informant-rated functional status, (2) informant-rated functional status and objective cognition (in those with MCI), and (3) self-rated functional status and objective cognition. These variables served as dependent variables in forward linear regression models, with demographics, stress, burden, depression, and self-efficacy as predictors.

Informants with higher stress rated individuals with MCI as having worse functional abilities relative to objective cognition. Individuals with MCI with worse self-efficacy rated their functional abilities as being worse compared to objective cognition. Informant-ratings were worse than self-ratings for informants with higher stress and individuals with MCI with higher self-efficacy.

This study highlights biases in subjective ratings of functional abilities in MCI. The risk for relative underreporting of functional abilities by individuals with higher stress levels aligns with previous research. Bias in individuals with MCI with higher self-efficacy may be due to anosognosia. Findings have implications for the use of subjective ratings for diagnostic purposes and as outcome measures.

Recent studies in Alzheimer’s disease (AD) have suggested that AD patients are not always able to rely on their feeling of familiarity to improve their memory decisions to the same extent as healthy participants. This underuse of familiarity in AD could result from a learned reinterpretation of fluency as a poor cue for memory that would prevent them to attribute a feeling of fluency to a previous encounter. The primary goal of this study was to determine whether AD patients could relearn the association between processing fluency and past exposure after being repeatedly exposed to situations where using this association improves the accuracy of their memory decisions.

Thirty-nine patients with probable AD were recruited and asked to complete several recognition tests. During these tests, participants were put either in a condition where the positive contingency between fluent processing and previous encounters with an item was systematically confirmed (intervention condition) or in a condition where there was no correlation between fluency and prior exposure (control condition). The efficacy of the intervention was evaluated at three time points (baseline, posttest, and 3-month follow-up).

Our results indicated that all AD patients do not benefit to the same extent from the training. Two variables appeared to influence the likelihood that participants increase and maintain their reliance on the fluency cues after the intervention: the ability to detect the fluency manipulation and the preservation of implicit metacognitive skills.

These findings indicate the importance of metacognition for inferential attribution processes in memory.