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Background: Lower cerebral blood flow (CBF) and excessive brain atrophy are linked to Alzheimer’s disease (AD). It is still undetermined whether reduced CBF precedes or follows brain tissue loss. Objective: We compared total CBF (tCBF), global cerebral perfusion (GCP), and volumes of AD-prone regions between cognitively normal (CN) and early amnestic mild cognitive impairment (aMCI) and tested their associations with cognitive performance to assess their predictive value for differentiation between CN and early aMCI. Methods: A total of 74 participants (mean age 69.9±6.2 years, 47 females) were classified into two groups: 50 CN and 24 aMCI, of whom 88% were early aMCI. tCBF, GCP, and global and regional brain volumetry were measured using phase-contrast and T1-weighted MRI. Neuropsychological tests tapping global cognition and four cognitive domains (memory, executive function, language, and visuospatial) were administered. Comparisons and associations were investigated using analyses of covariance (ANCOVA) and linear regression analyses, respectively. Results: Women had significantly higher GCP than men. Both, tCBF and GCP were significantly reduced in aMCI compared with CN, while differences in volumes of cerebral gray matter, white matter, and AD-prone regions were not significant. tCBF and GCP were significantly associated with global cognition (standardized beta (stβ) = 0.324 and stβ= 0.326) and with memory scores (stβ≥0.297 and stβ≥0.264) across all participants. Associations of tCBF and GCP with memory scores were also significant in CN (stβ= 0.327 and stβ= 0.284) and in aMCI (stβ= 0.627 and stβ= 0.485). Conclusion: Reduced tCBF and GCP are sensitive biomarkers of early aMCI that likely precede brain tissue loss.

Background: LASSI-L is a novel neuropsychological test specifically designed for the early diagnosis of Alzheimer’s disease (AD) based on semantic interference. Objective: To examine the cognitive and neural underpinnings of the failure to recover from proactive semantic and retroactive semantic interference. Methods: One hundred and fifty-five patients consulting for memory loss were included. Patients underwent neuropsychological assessment, including the LASSI-L, and FDG-PET imaging. They were categorized as subjective memory complaints (SMC) (n=32), pre-mild cognitive impairment (MCI) due to AD (Pre-MCI) (n=39), MCI due to AD (MCI-AD) (n=71), and MCI without evidence of neurodegeneration (MCI-NN) (n=13). Voxel-based brain mapping and metabolic network connectivity analyses were conducted. Results: A significant group effect was found for all the LASSI-L scores. LASSI-L scores measuring failure to recover from proactive semantic interference and retroactive semantic interference were predicted by other neuropsychological tests with a precision of 64.1 and 44.8%. The LASSI-L scores were associated with brain metabolism in the bilateral precuneus, superior, middle and inferior temporal gyri, fusiform, angular, superior and inferior parietal lobule, superior, middle and inferior occipital gyri, lingual gyrus, and posterior cingulate. Connectivity analysis revealed a decrease of node degree and centrality in posterior cingulate in patients showing frPSI. Conclusion: Episodic memory dysfunction and the involvement of the medial temporal lobe, precuneus and posterior cingulate constitute the basis of the failure to recover from proactive semantic interference and retroactive semantic interference. These findings support the role of the LASSI-L in the detection, monitoring and outcome prediction during the early stages of AD.

Cross-cultural differences in the association between neuropsychiatric symptoms and Alzheimer's disease (AD) biomarkers are not well understood. This study aimed to (1) compare depressive symptoms and frequency of reported apathy across diagnostic groups of participants with normal cognition (CN), mild cognitive impairment (MCI), and dementia, as well as ethnic groups of Hispanic Americans (HA) and European Americans (EA); (2) evaluate the relationship between depression and apathy with Aβ deposition and brain atrophy. Statistical analyses included ANCOVAs, chi-squared, nonparametric tests, correlations, and logistic regressions. Higher scores on the Geriatric Depression Scale (GDS-15) were reported in the MCI and dementia cohorts, while older age corresponded with lower GDS-15 scores. The frequency of apathy differed across diagnoses within each ethnicity, but not when comparing ethnic groups. Reduced volume in the rostral anterior cingulate cortex (ACC) significantly correlated with and predicted apathy for the total sample after applying false discovery rate corrections (FDR), controlling for covariates. The EA group separately demonstrated a significant negative relationship between apathy and superior frontal volume, while for HA, there was a relationship between rostral ACC volume and apathy. Apathy corresponded with higher Aβ levels for the total sample and for the CN and HA groups.

Objective: To determine whether cognition is associated with mortality among older US adults. Methods: We studied 5,989 National Health and Nutrition Examination Survey participants age 60+ in years 1999–2014 with mortality follow-up through 2015. Cognitive function was measured in one standard deviation decrements using the Digit Symbol Substitution Test (DSST), Animal Fluency (AnFl), and two Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) tests. Results: Each decrement in cognitive function was associated with increased risk of mortality overall (DSST HR: 1.36, 95% CI: 1.25, 1.48), among women only (AnFl: 1.51, 95% CI: 1.02, 2.24), and among those with less than a high school education only (AnFl HR: 1.46, 95% CI: 1.09, 1.97; CERAD-WL HR: 1.34, 95% CI: 1.07, 1.67; and CERAD-DR HR: 1.38, 95% CI: 1.05, 1.82). Discussion: Among US adults, lower cognitive functioning was associated with mortality; associations were stronger among women and those with less education.

Despite the growing emphasis to identify early biological markers that can detect the progressive accumulation of brain pathology in the complex pathophysiologic cascade that occurs in Alzheimer’s disease (AD), we continue to employ the same neuropsychological paradigms that were developed to detect dementia or frank cognitive impairment. It has become increasingly clear that we cannot expect to measure clinically meaningful change in relationship to these emerging preclinical biomarkers using these traditional cognitive assessment paradigms, nor will we advance the efforts to identify the earliest cognitive changes that emerge in AD. Over the last decade, a few novel promising cognitive assessment paradigms have emerged that have shown promise in identifying subtle cognitive deficits in AD which aids in early detection and monitoring of meaningful cognitive change over time. Some of these cognitive assessment paradigms are reviewed here, including semantic interference, semantic intrusion errors, memory binding, and binding of face and name associations. These paradigms may be useful for AD clinical trials focused on secondary prevention if there is sufficient rigor to suggest that they correlate with AD biomarkers, having robust sensitivity, specificity, and predictive utility among culturally and linguistically diverse populations at-risk for AD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01192-0.

Background: Machine learning is a promising tool for biomarker-based diagnosis of Alzheimer’s disease (AD). Performing multimodal feature selection and studying the interaction between biological and clinical AD can help to improve the performance of the diagnosis models. Objective: This study aims to formulate a feature ranking metric based on the mutual information index to assess the relevance and redundancy of regional biomarkers and improve the AD classification accuracy. Methods: From the Alzheimer’s Disease Neuroimaging Initiative (ADNI), 722 participants with three modalities, including florbetapir-PET, flortaucipir-PET, and MRI, were studied. The multivariate mutual information metric was utilized to capture the redundancy and complementarity of the predictors and develop a feature ranking approach. This was followed by evaluating the capability of single-modal and multimodal biomarkers in predicting the cognitive stage. Results: Although amyloid-β deposition is an earlier event in the disease trajectory, tau PET with feature selection yielded a higher early-stage classification F1-score (65.4%) compared to amyloid-β PET (63.3%) and MRI (63.2%). The SVC multimodal scenario with feature selection improved the F1-score to 70.0% and 71.8% for the early and late-stage, respectively. When age and risk factors were included, the scores improved by 2 to 4%. The Amyloid-Tau-Neurodegeneration [AT(N)] framework helped to interpret the classification results for different biomarker categories. Conclusion: The results underscore the utility of a novel feature selection approach to reduce the dimensionality of multimodal datasets and enhance model performance. The AT(N) biomarker framework can help to explore the misclassified cases by revealing the relationship between neuropathological biomarkers and cognition.

There is currently a lack of consensus among neuropsychologists about which cognitive assessment paradigms hold the most promise in identifying subtle cognitive deficits in preclinical Alzheimer's Disease (AD) and which are most useful for monitoring risk of cognitive deterioration. Many widely used instruments are older versions of tests originally developed for the assessment of dementia or traumatic brain injury. Current efforts to digitize these measures provides more uniform and remote assessment, which is an advancement, but does not reflect significant changes in paradigmatic underpinnings or recent advances in cognitive neuroscience.This work provides an overview of novel Cognitive Challenge Tests (CCTs) that employ semantic interference paradigms that uniquely measure the failure to recover from proactive semantic interference (frPSI). Other salient methods to measure meaningful cognitive change in early stage AD are also presented, as well as how they compare with traditional neuropsychological assessments. Finally, future directions for the development of more effective assessment paradigms are discussed.frPSI is a cognitive marker which measures the persistent inability to learn new semantically competing stimuli despite multiple opportunities to do so. frPSI and deficits in semantic inhibitory control have repeatedly shown utility for the early detection of AD during its preclinical stages. These novel cognitive markers have been related to various biomarkers of AD and neurodegeneration among culturally diverse older adults.To meet the critical needs of a rapidly evolving field, cognitive assessment instruments must show sufficient scientific rigor including robust sensitivity, specificity, and predictive utility among culturally and linguistically diverse populations and importantly, be correlated to AD biomarkers. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

We examined the association between bilingualism, executive function (EF), and brain volume in older monolinguals and bilinguals who spoke English, Spanish, or both, and were cognitively normal (CN) or diagnosed with Mild Cognitive Impairment (MCI) or dementia. Gray matter volume (GMV) was higher in language and EF brain regions among bilinguals, but no differences were found in memory regions. Neuropsychological performance did not vary across language groups over time; however, bilinguals exhibited reduced Stroop interference and lower scores on Digit Span Backwards and category fluency. Higher scores on Digit Span Backwards were associated with a younger age of English acquisition, and a greater degree of balanced bilingualism was associated with lower scores in category fluency. The initial age of cognitive decline did not differ between language groups. The influence of bilingualism appears to be reflected in increased GMV in language and EF regions, and to a lesser degree, in EF.

Given the interdependence of multiple factors in age-related vestibular loss (e.g., balance, vision, cognition), it is important to examine the individual contributions of these factors with ARVL. While the relationship between the vestibular and visual systems has been well studied ( Bronstein et al., 2015 ), little is known about the association of the peripheral vestibular system with neurodegenerative disorders ( Cronin et al., 2017 ). Further, emerging research developments implicate the vestibular system as an opportunity for examining brain function beyond balance, and into other areas, such as cognition and psychological functioning. Additionally, the bidirectional impact of psychological functioning is understudied in ARVL. Recognition of ARVL as part of a multifaceted aging process will help guide the development of integrated interventions for patients who remain at risk for decline. In this review, we will discuss a wide variety of characteristics of the peripheral vestibular system and ARVL, how it relates to neurodegenerative diseases, and correlations between ARVL and balance, vision, cognitive, and psychological dysfunction. We also discuss clinical implications as well as future directions for research, with an emphasis on improving care for patients with ARVL.

Background: Susceptibility to proactive semantic interference (PSI) and the inability to ameliorate these difficulties with one additional learning trial have repeatedly been implicated as early features of incipient Alzheimer’s disease (AD). Unfortunately, persistent failure to recover from PSI (frPSI) after repeated learning trials, are not captured by existing memory measures, or been examined in pre-mild cognitive impairment (PreMCI). Objective: A novel Cognitive Stress Test (CST) was employed to measure the impact of PSI, initial failure to recover from PSI and persistent effects of PSI, despite multiple learning trials of the new to-be-remembered material (pfrPSI). We hypothesized that PSI deficits on the CST would persist in both PreMCI and amnestic MCI (aMCI) groups over repeated learning trials when compared to cognitively unimpaired (CU) older adults. Methods: One hundred fifty older adults (69 CU, 31 PreMCI, and 50 aMCI) underwent a standardized clinical and neuropsychological evaluation. The CST was independent of diagnostic classification. Results: Even after adjusting for strength of initial learning, aMCI and PreMCI groups demonstrated greater persistent PSI (pfrPSI) relative to the CU group despite repeated learning trials of List B. Further, the aMCI group made a higher number of semantic intrusion errors relative to the PreMCI and CU groups on all List B Cued Recall trials. Conclusion: Persistent PSI appears to be a common feature of aMCI and PreMCI. The possible theoretical mechanisms and empirical implications of these new findings are discussed.

The increasing prevalence of AD among Hispanics calls for a need for examining factors that affect cognitive functioning and risk of AD among Hispanic older adults. The current study examined cognitive functioning among older Hispanic adults living in the U.S. from two Hispanic regions, South America and the Caribbean, in relation to the country where education was obtained. Participants (n = 139) were stratified into groups based on Hispanic education region and diagnostic categories: cognitively normal and amnestic MCI (aMCI). Results of Pearson correlations showed that among Hispanic Americans in general, there were significant positive correlations between the country of education to performance on measures of episodic, verbal, and word list tests. When examined separately by region and diagnosis, only cognitively normal (CN) South Americans showed significant relationships between country of education and cognitive functioning in these areas. Results of general linear models controlling for education identified differences in neuropsychological performance between groups with the CN groups demonstrating better performance than the aMCI groups within each region. Overall, it was evident that relationships between years of education obtained outside of the U.S. and cognitive functioning were not similar among individuals from these two disparate Spanish speaking regions. This is the first study to examine the country where education was obtained among individuals from countries located in different regions with different cultures that may influence their education and cognitive development throughout life. Findings contribute to the cross-cultural neuropsychological literature in understanding factors that are unique to Hispanic older adults at risk for developing AD.

Background: Perivascular spaces (PVS) are fluid-filled compartments surrounding small intracerebral vessels that transport fluid and clear waste. Objective: We examined associations between PVS count, vascular and neurodegenerative risk factors, and cognitive status among the predominantly Hispanic participants of the FL-VIP Study of Alzheimer’s Disease Risk. Methods: Using brain MRI (n = 228), we counted PVS in single axial image through the basal ganglia (BG) and centrum semiovale (CSO). PVS per region were scored as 0 (none), 1 (40). Generalized linear models examined PVS associations with vascular risk factors and a composite vascular comorbidity risk (VASCom) score. Results: Our sample (mean age 72±8 years, 61% women, 60% Hispanic, mean education 15±4 years, 33% APOE4 carriers) was 59% hypertensive, 21% diabetic, 66% hypercholesteremic, and 30% obese. Mean VASCom score was 2.3±1.6. PVS scores ranged from 0–4 in the BG (mean 1.3±0.7) and CSO (mean 1.2±0.9), and 0–7 combined (mean 2.5±1.4). In multivariable regression models, BG PVS was associated with age (β= 0.03/year, p

Background: Plasma NfL (pNfL) levels are elevated in many neurological disorders. However, the utility of pNfL in a clinical setting has not been established. Objective: In a cohort of diverse older participants, we examined: 1) the association of pNfL to age, sex, Hispanic ethnicity, diagnosis, and structural and amyloid imaging biomarkers; and 2) its association to baseline and longitudinal cognitive and functional performance. Methods: 309 subjects were classified at baseline as cognitively normal (CN) or with cognitive impairment. Most subjects had structural MRI and amyloid PET scans. The most frequent etiological diagnosis was Alzheimer’s disease (AD), but other neurological and neuropsychiatric disorders were also represented. We assessed the relationship of pNfL to cognitive and functional status, primary etiology, imaging biomarkers, and to cognitive and functional decline. Results: pNfL increased with age, degree of hippocampal atrophy, and amyloid load, and was higher in females among CN subjects, but was not associated with Hispanic ethnicity. Compared to CN subjects, pNfL was elevated among those with AD or FTLD, but not those with neuropsychiatric or other disorders. Hippocampal atrophy, amyloid positivity and higher pNfL levels each added unique variance in predicting greater functional impairment on the CDR-SB at baseline. Higher baseline pNfL levels also predicted greater cognitive and functional decline after accounting for hippocampal atrophy and memory scores at baseline. Conclusion: pNfL may have a complementary and supportive role to brain imaging and cognitive testing in a memory disorder evaluation, although its diagnostic sensitivity and specificity as a stand-alone measure is modest. In the absence of expensive neuroimaging tests, pNfL could be used for differentiating neurodegenerative disease from neuropsychiatric disorders.

Introduction: Among persons with amnestic mild cognitive impairment (aMCI), intrusion errors on subscales that measure proactive semantic interference (PSI) may be among the earliest behavioral markers of elevated Alzheimer’s disease brain pathology. While there has been considerable cross-sectional work in the area, it is presently unknown whether semantic intrusion errors are predictive of progression of cognitive impairment in aMCI or PreMCI (not cognitively normal but not meeting full criteria for MCI). Methods: This study examined the extent to which the percentage of semantic intrusion errors (PIE) based on total responses on a novel cognitive stress test, the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), could predict clinical/cognitive outcomes over an average 26-month period in older adults initially diagnosed with aMCI, PreMCI, and normal cognition. Results: On the LASSI-L subscale sensitive to PSI, a PIE cut point of 44% intrusion errors distinguished between those at-risk individuals with PreMCI who progressed to MCI over time compared to individuals with PreMCI who reverted to normal on longitudinal follow-up. Importantly, PIE was able to accurately predict 83.3% of aMCI individuals who later progressed to dementia. Discussion: These preliminary findings indicate that PIE on LASSI-L subscales that measure PSI may be a useful predictor of clinical progression overtime in at-risk older adults.

During the prodromal stage of Alzheimer’s disease (AD), neurodegenerative changes can be identified by measuring volumetric loss in AD-prone brain regions on MRI. Cognitive assessments sensitive enough to measure the early brain-behavior manifestations of AD and correlate with biomarkers of neurodegeneration are needed to identify and monitor individuals at risk for dementia. Weak sensitivity to early cognitive change has been one major limitation of traditionally used assessment tools. In this study, we focused on expanding our previous work by determining whether a digitized cognitive stress test, the Loewenstein-Acevedo Scales for Sematic Interference and Learning, Brief Computerized Version (LASSI-BC) could differentiate between Cognitively Unimpaired (CU) and amnestic Mild Cognitive Impairment (aMCI) groups. A second focus was to correlate LASSI-BC performance to volumetric reductions in AD-prone regions. Data was gathered from 127 older adults who were comprehensively evaluated and administered the LASSI-BC. Eighty-seven of these participants (51 CU; 36 aMCI) underwent MRI imaging. The volumes of 12 AD-prone brain regions were related to LASSI-BC and other memory indices correcting for False Discovery Rate (FDR). Results indicated that, even after adjusting for initial learning ability, the failure to recover from proactive semantic interference (frPSI) on the LASSI-BC differentiated between CU and aMCI groups. An optimal combination of frPSI and initial learning strength on the LASSI-BC yielded an area under the ROC curve of .876 (76.1% sensitivity, 82.7% specificity). Further, LASSI-BC measures of frPSI were associated with volumetric reductions in AD prone regions including the hippocampus, amygdala, inferior temporal lobes, precuneus and posterior cingulate.

Background: The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) is an increasingly utilized cognitive stress test designed to identify early cognitive changes associated with incipient neurodegenerative disease. Objective: To examine previously derived cut-points for cognitively unimpaired older adults that were suggestive of performance impairment on multiple subscales of the LASSI-L. These cut-points were applied to a new sample of older adults who were cognitive healthy controls (HC: n = 26) and those on the Alzheimer’s disease (AD) continuum from early stage mild cognitive impairment (EMCI: n = 28), late stage MCI (LMCI: n = 18) to mild AD (AD: n = 27). Methods: All participants were administered the LASSI-L. All cognitively impaired participants were PET amyloid positive which likely reflects underlying AD neuropathology, while cognitively normal counterparts were deemed to have amyloid negative scans. Results: There was a monotonic relationship between the number of deficits on LASSI-L subscales and independent classification of study groups with greater severity of cognitive impairment. Importantly, taken together, impairment on maximum learning ability and measures of proactive semantic interference (both reflected by cued recall and intrusion errors) correctly classified 74.1% of EMCI, 94.4% of LMCI, and 96.3% of AD. Only 7.7% of HC were incorrectly classified as having impairments. Conclusion: A modest number of LASSI-L subscales taking approximately 8 minutes to administer, had excellent discriminative ability using established cut-offs among individuals with presumptive stages of AD. This has potential implications for both clinical practice and clinical research settings targeting AD during early prodromal stages.

Objective To investigate the association between the functional activities questionnaire (FAQ) and brain biomarkers (bilateral hippocampal volume [HV], bilateral entorhinal volume [ERV], and entorhinal cortical thickness [ERT]) in cognitively normal (CN) individuals, mild cognitive impairment (MCI), or dementia. Method In total, 226 participants (137 females; mean age = 71.76, SD = 7.93; Hispanic Americans = 137; European Americans = 89) were assessed with a comprehensive clinical examination, a neuropsychological battery, a structural magnetic resonance imaging, and were classified as CN or diagnosed with MCI or dementia. Linear regression analyses examined the association between functional activities as measured by the FAQ on brain biomarkers, including HV, ERV, and ERT, controlling for age, education, global cognition, gender, and ethnicity. Results The FAQ significantly predicted HV, ERV, and ERT for the entire sample. However, this association was not significant for ERV and ERT when excluding the dementia group. The FAQ score remained a significant predictor of HV for the non-dementia group. Age, education, gender, ethnicity, Montreal Cognitive Assessment score, and FAQ were also significant predictors of HV for the overall sample, suggesting that younger Hispanic females with fewer years of education, higher global mental status, and better functioning, were more likely to have larger HV. Conclusion FAQ scores were related to HV in older adults across clinical groups (CN, MCI, and dementia), but its association with the entorhinal cortex was driven by individuals with dementia. Demographic variables, including ethnicity, additionally influenced these associations.

Objective:To assess the influence of mild behavioral impairment (MBI) on the cognitive performance of older adults who are cognitively healthy or have mild cognitive impairment (MCI).Methods:Secondary data analysis of a sample (n = 497) of older adults from the Florida Alzheimer’s Disease Research Center who were either cognitively healthy (n = 285) or diagnosed with MCI (n = 212). Over half of the sample (n = 255) met the operationalized diagnostic criteria for MBI. Cognitive domains of executive function, attention, short-term memory, and episodic memory were assessed using a battery of neuropsychological tests.Results:Older adults with MBI performed worse on tasks of executive function, attention, and episodic memory compared to those without MBI. A significant interaction revealed that persons with MBI and MCI performed worse on tasks of episodic memory compared to individuals with only MCI, but no significant differences were found in performance in cognitively healthy older adults with or without MBI on this cognitive domain. As expected, cognitively healthy older adults performed better than individuals with MCI on every domain of cognition.Conclusions:The present study found evidence that independent of cognitive status, individuals with MBI performed worse on tests of executive function, attention, and episodic memory than individuals without MBI. Additionally, those with MCI and MBI perform significantly worse on episodic memory tasks than individuals with only MCI. These results provide support for a unique cognitive phenotype associated with MBI and highlight the necessity for assessing both cognitive and behavioral symptoms.

OBJECTIVES: This study examined the association of cultural factors and literacy to neuropsychological performance and measures of regional brain atrophy among Hispanic elders diagnosed with amnestic Mild Cognitive Impairment (aMCI). METHOD: Acculturation and literacy levels were measured among 45 subjects tested in Spanish; their primary language. Scores for measures of memory, executive functioning, and verbal fluency, as well as volumetric analysis of MRI scans of left hemisphere structures commonly affected by Alzheimer’s disease (AD) were examined. Linear regression models were employed to examine the association of acculturation and literacy to neuropsychological performance and MRI measures. RESULTS: After controlling for age, higher literacy levels were associated with better performance on phonemic verbal fluency (r = 0.300, p < .05), while higher levels of acculturation to the U.S. was associated with poorer performance on category verbal fluency (r = 0.300, p < .05). There was a significant inverse relationship after controlling for age between literacy and the left entorhinal cortex (r = −0.455, p < .05), left precuneus (r = −0.457, p < .05), and left posterior cingulate (r = −0.415, p < .05). CONCLUSIONS: Results of the current pilot study indicate that high acculturation to the U.S. among aMCI immigrants from Latin-American countries may hinder performance on verbal learning measures when they are administered in one’s primary language. Moreover, in this cohort, a higher literacy level, which is indicative of greater cognitive reserve, was associated with better performance in language measures, but with greater atrophy in brain regions susceptible to neurodegenerative disease. These preliminary findings should be further examined among larger cohorts and using more diverse measures, which capture other cultural constructs.

Increasing rates of dementia spectrum disorders among Spanish-speaking geriatric populations necessitate the development of culturally appropriate cognitive screening tests that can identify neurodegenerative disorders in their earliest stages when emerging disease-modifying treatments are most likely to be effective. This scoping review identified 26 brief Spanish language cognitive screening tools (

The effect of acculturation on cognition was examined among 142 older Hispanics: cognitively normal [CN; n = 70], Mild Cognitive Impairment, amnestic [aMCI; n = 27], and Dementia [D; n = 45]. Acculturation levels (high vs. low) were determined using the Short Acculturation Scale for Hispanics (SASH). ANCOVAs used a wide variety of neuropsychological tests as independent variables controlling for age and education. Among CN subjects, the highly acculturated group performed better on Logical Memory delayed recall (LM-II) [F(1, 56) = 9.26, p < .001, [Formula: see text] = 0.14], Digit Span Forward [F(1, 56) = 4.37, p < .05, [Formula: see text] = 0.07], Trail Making Test A [F(1, 56) = 7.74, p < .05, [Formula: see text] = 0.12], and Trail Making Test B [F(1, 56) = 4.66, p = .03, [Formula: see text] = 0.08], indicating that high acculturation was associated with a better performance on tests of episodic memory, auditory attention, working memory, cognitive flexibility, and processing speed among CN Hispanics. ANCOVA analyses were not significant among the other groups. In the absence of acculturation scales in clinical practice, caution should be exerted when interpreting neurocognitive results.

BACKGROUND Modifiable vascular risk factors (VRF) have been implicated in cognitive impairment. OBJECTIVE We compared the prediction of cognitive performance between the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score, a validated tool to estimate dementia risk using VRF, and the Northern Manhattan Study (NOMAS) global vascular risk score (GVRS), created to predict vascular events. METHODS The CAIDE and GVRS scores were calculated based on baseline VRF among 1,290 stroke-free participants in the prospective population-based NOMAS MRI cohort (mean age 64±8 years, 60% women; 66% Hispanic, 17% Black, 15% White; 46% completed high school). Domain-specific Z-scores were derived for episodic and semantic memory, executive function, and processing speed, and averaged to calculate global cognition. RESULTS The CAIDE score was associated with worse global cognition at initial assessment (Beta per SD = -0.347, p

Background: Difficulties in inhibition and self-monitoring are early features of incipient Alzheimer’s disease and may manifest as susceptibility to proactive semantic interference. However, due to limitations of traditional memory assessment paradigms, recovery from interference effects following repeated learning opportunities has not been explored. Objective: This study employed a novel computerized list learning test consisting of repeated learning trials to assess recovery from proactive and retroactive semantic interference. Design: The design was cross-sectional. Setting: Participants were recruited from the community as part of a longitudinal study on normal and abnormal aging. Participants: The sample consisted of 46 cognitively normal individuals and 30 participants with amnestic mild cognitive impairment. Measurements: Participants were administered the Cognitive Stress Test and traditional neuropsychological measures. Step-wise logistic regression was applied to determine which Cognitive Stress Test measures best discriminated between diagnostic groups. This was followed by receiver operating characteristic analyses. Results: Cued A3 recall, Cued B3 recall and Cued B2 intrusions were all independent predictors of diagnostic status. The overall predictive utility of the model yielded 75.9% sensitivity, 91.1% specificity, and an overall correct classification rate of 85.1%. When these variables were jointly entered into receiver operating characteristic analyses, the area under the curve was .923 (p

Background and ObjectivesThe goal of this work was to determine the relationship between diffusion microstructure and early changes in Alzheimer disease (AD) severity as assessed by clinical diagnosis, cognitive performance, dementia severity, and plasma concentrations of neurofilament light chain.MethodsDiffusion MRI scans were collected on cognitively normal participants (CN) and patients with early mild cognitive impairment (EMCI), late mild cognitive impairment, and AD. Free water (FW) and FW-corrected fractional anisotropy were calculated in the locus coeruleus to transentorhinal cortex tract, 4 magnocellular regions of the basal forebrain (e.g., nucleus basalis of Meynert), entorhinal cortex, and hippocampus. All patients underwent a battery of cognitive assessments; neurofilament light chain levels were measured in plasma samples.ResultsFW was significantly higher in patients with EMCI compared to CN in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus (mean Cohen d = 0.54; pfdr < 0.05). FW was significantly higher in those with AD compared to CN in all the examined regions (mean Cohen d = 1.41; pfdr < 0.01). In addition, FW in the hippocampus, entorhinal cortex, nucleus basalis of Meynert, and locus coeruleus to transentorhinal cortex tract positively correlated with all 5 cognitive impairment metrics and neurofilament light chain levels (mean r2 = 0.10; pfdr < 0.05).DiscussionThese results show that higher FW is associated with greater clinical diagnosis severity, cognitive impairment, and neurofilament light chain. They also suggest that FW elevation occurs in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus in the transition from CN to EMCI, while other basal forebrain regions and the entorhinal cortex are not affected until a later stage of AD. FW is a clinically relevant and noninvasive early marker of structural changes related to cognitive impairment.

Poor sleep quality is a known risk factor for Alzheimer's disease. This longitudinal imaging study aimed to determine the acceleration in the rates of tissue loss in cognitively critical brain regions due to poor sleep in healthy elderly individuals. Cognitively-normal healthy individuals, aged ≥60 years, reported Pittsburgh Sleep Quality Index (PSQI) and underwent baseline and 2-year follow-up magnetic resonance imaging brain scans. The links between self-reported sleep quality, rates of tissue loss in cognitively-critical brain regions, and white matter hyperintensity load were assessed. A total of 48 subjects were classified into normal (n = 23; PSQI score5) and poor sleepers (n = 25; PSQI score ≥5). The two groups were not significantly different in terms of age, gender, years of education, ethnicity, handedness, body mass index, and cognitive performance. Compared to normal sleepers, poor sleepers exhibited much faster rates of volume loss, over threefold in the right hippocampus and fivefold in the right posterior cingulate over 2 years. In contrast, there were no significant differences in the rates of volume loss in the cerebral and cerebellar grey and white matter between the two groups. Rates of volume loss in the right posterior cingulate were negatively associated with global PSQI scores. Poor sleep significantly accelerates volume loss in the right hippocampus and the right posterior cingulate cortex. These findings demonstrate that self-reported sleep quality explains inter-individual differences in the rates of volume loss in cognitively-critical brain regions in healthy older adults and provide a strong impetus to offer sleep interventions to cognitively normal older adults who are poor sleepers.