Effects of lithium on serum Brain-Derived Neurotrophic Factor in Alzheimer's patients with agitation.

BACKGROUND: There is ample evidence in animal models that lithium increases Brain-Derived Neurotrophic Factor (BDNF) with supporting evidence in human studies. Little is known, however, about the effects of lithium on BDNF in Alzheimer's Dementia (AD). In one study of patients with Mild Cognitive Impairment, serum BDNF increased after treatment with lithium. These patients also showed mild improvement in cognitive function. OBJECTIVES: To evaluate low-dose lithium treatment of agitation in Alzheimer's disease (AD). METHOD: We measured levels of BDNF in patients treated with lithium prior to and after a 12-week randomized placebo-controlled trial. RESULTS: BDNF levels did not change significantly and were not associated with improvement in overall neuropsychiatric symptoms or in cognitive function. CONCLUSIONS: More research is needed to understand the potential effects of lithium on BDNF in AD including whether its use might be dependent on the stage of cognitive decline and dementia.

Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial.

BACKGROUND: A case series suggested efficacy for lithium to treat agitation in dementia, but no placebo-controlled trials have been conducted. OBJECTIVES: To evaluate low-dose lithium treatment of agitation in Alzheimer's disease (AD). METHOD: In a four-site trial, patients with AD and agitation/aggression score ≥4 on the Neuropsychiatric Inventory (NPI) were randomized, double-blind, to lithium carbonate 150-600 mg daily or placebo for 12 weeks. Primary efficacy outcome was change in NPI agitation/aggression; secondary efficacy outcome was treatment response (30% reduction in NPI score for agitation/aggression plus psychosis and a Clinical Global Impression (CGI) score of much or very much improved). Safety profile of lithium was assessed. RESULTS: Fifty-eight of 77 patients (75.3%) completed the trial. In linear mixed effects model analyses, lithium was not significantly superior to placebo for agitation/aggression. Proportion of responders was 31.6% on lithium and 17.9% on placebo (χ2=1.26, p = 0.26). Moderate or marked improvement (CGI) was greater on lithium (10/38=36.8%) than placebo (0/39=0%, Fisher's exact test p <0.001). In exploratory analyses, improvement on lithium was greater than placebo on NPI delusions and irritability/lability (p's<0.05). Lithium showed greater reduction than placebo in patients with high Young Mania Rating Scale scores (ß=5.06; 95%CI,1.18 to 8.94, p = 0.01). Oral dose and serum levels demonstrated similar associations with efficacy outcomes. Lithium did not differ significantly from placebo on safety outcomes. CONCLUSIONS: Low-dose lithium was not efficacious in treating agitation but was associated with global clinical improvement and excellent safety. A larger trial may be warranted of likely lithium-responsive behavioral symptoms that overlap with mania.

Semantic intrusion errors as a function of age, amyloid, and volumetric loss: a confirmatory path analysis.

OBJECTIVE: To examine the direct and indirect effects of age, APOE ϵ4 genotype, amyloid positivity, and volumetric reductions in AD-prone brain regions as it relates to semantic intrusion errors reflecting proactive semantic interference (PSI) and the failure to recover from proactive semantic interference (frPSI) on the Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L), a cognitive stress test that has been consistently more predictive of preclinical and prodromal Alzheimer's disease (AD) than traditional list-learning tests. DESIGN: Cross-sectional study. SETTING: 1Florida Alzheimer's Disease Research Center baseline study. PARTICIPANTS: Two-hundred and twelve participants with Mini-Mental State Examination (MMSE) score above 16 and a broad array of cognitive diagnoses ranging from cognitively normal (CN) to dementia, of whom 58% were female, mean age of 72.1 (SD 7.9). MEASURES: Participants underwent extensive clinical and neuropsychological evaluations, MR and amyloid Positron Emission Tomography/Computer/Computer Tomography (PET/CT) imaging, and analyses of APOE ϵ4 genotype. Confirmatory path analyses were conducted in the structural equation modeling framework that estimated multiple equations simultaneously while controlling for important covariates such as sex, education, language of evaluation, and global cognitive impairment. RESULTS: Both amyloid positivity and decreased brain volumes in AD-prone regions were directly related to LASSI-L Cued B1 and Cued B2 intrusions (sensitive to PSI and frPSI effects) even after controlling for covariates. APOE ϵ4 status did not evidence direct effects on these LASSI-L cognitive markers, but rather exerted their effects on amyloid positivity, which in turn related to PSI and frPSI. Similarly, age did not have a direct relationship with LASSI-L scores, but exerted its effects indirectly through amyloid positivity and volumes of AD-prone brain regions. CONCLUSIONS: Our study provides insight into the relationships among age, APOE ϵ4, amyloid, and brain volumetric reductions as it relates to semantic intrusion errors. The investigation expands our understanding of the underpinnings of PSI and frPSI intrusions in a large cohort.

Intrusion Errors and Progression of Cognitive Deficits in Older Adults with Mild Cognitive Impairment and PreMCI States.

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.

A Novel Cognitive Stress Test for the Detection of Preclinical Alzheimer Disease: Discriminative Properties and Relation to Amyloid Load.

OBJECTIVE: To examine the utility of a novel "cognitive stress test" to detect subtle cognitive impairments and amyloid load within the brains of neuropsychologically normal community-dwelling elders. METHODS: Participants diagnosed as cognitively normal (CN), subjective memory impairment (SMI), mild cognitive impairment (MCI), and preclinical mild cognitive impairment (PreMCI) were administered the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), a sensitive test of proactive semantic interference (PSI), retroactive semantic interference, and, uniquely, the ability to recover from the effects of PSI. Ninety-three subjects (31 men and 62 women) were recruited from three academic institutions in a research consortium. A subset of these individuals underwent 18F florbetapir positron emission tomography scanning. Relative percentages of impairment for each diagnostic group on the LASSI-L were calculated by χ(2) and Fisher's exact tests. Spearman's rho was used to examine associations between amyloid load and different cognitive measures. RESULTS: LASSI-L deficits were identified among 89% of those with MCI, 47% with PreMCI, 33% with SMI, and 13% classified as CN. CN subjects had no difficulties with recovery from PSI, whereas SMI, preMCI, and MCI participants evidenced deficits in recovery from PSI effects. Among a subgroup of participants with normal scores on traditional neuropsychological tests, the strong associations were between the failure to recover from the effects of PSI and amyloid load in the brain. CONCLUSION: Failure to recover or compensate for the effects of PSI on the LASSI-L distinguishes the LASSI-L from other widely used neuropsychological tests and appears to be sensitive to subtle cognitive impairments and increasing amyloid load.

APOE ε4 carriers may undergo synaptic damage conferring risk of Alzheimer's disease.

INTRODUCTION: Pathogenesis of Alzheimer's disease (AD) in apolipoprotein E ε4 (APOE ε4) carriers remains unclear. We hypothesize that APOE isoforms have differential effects on synaptic function. METHODS: We compared levels of CSF neurogranin (Ng) between APOE ε4 carriers and noncarriers in 399 subjects with normal cognition, mild cognitive impairment (MCI), and AD. We examined associations between Ng levels and age, education, gender, CSF-Aß42, and tau protein. RESULTS: Neurogranin levels were significantly higher in APOE ε4 carriers compared to APOE ε4 noncarriers with MCI. Levels of Ng between the APOE ε4 carriers and APOE ε4 noncarriers with AD did not differ. Ng levels were correlated with MMSE and levels of tau and Aß42. DISCUSSION: Significantly higher CSF Ng levels in APOE ε4 carriers with MCI may reflect synaptic injury underlying early cognitive impairment. Neurogranin may be an early biomarker of AD and important for disease diagnosis and timing of intervention in APOE ε4 carriers.

An evaluation of deficits in semantic cueing and proactive and retroactive interference as early features of Alzheimer's disease.

OBJECTIVES: To determine the degree to which susceptibility to different types of semantic interference may reflect the initial manifestations of early Alzheimer's disease (AD) beyond the effects of global memory impairment. METHODS: Normal elderly (NE) subjects (n = 47), subjects with amnestic mild cognitive impairment (aMCI; n = 34), and subjects with probable AD (n = 40) were evaluated by using a unique cued recall paradigm that allowed for evaluation of both proactive and retroactive interference effects while controlling for global memory impairment (i.e., Loewenstein-Acevedo Scales of Semantic Interference and Learning [LASSI-L] procedure). RESULTS: Controlling for overall memory impairment, aMCI subjects had much greater proactive and retroactive interference effects than NE subjects. LASSI-L indices of learning by using cued recall revealed high levels of sensitivity and specificity, with an overall correct classification rate of 90%. These measures provided better discrimination than traditional neuropsychological measures of memory function. CONCLUSIONS: The LASSI-L paradigm is unique and unlike other assessments of memory in that items posed for cued recall are explicitly presented, and semantic interference and cueing effects can be assessed while controlling for initial level of memory impairment. This is a powerful procedure that allows the participant to serve as his or her own control. The high levels of discrimination between subjects with aMCI and normal cognition that exceeded traditional neuropsychological measures makes the LASSI-L worthy of further research in the detection of early AD.

The computerized LASSI-BC Test versus the Standard LASSI-L Paper-and-Pencil Version in Community-Based-Samples.

Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical AD determined by Aß load using PET. The goal of this study was to compare a new computerized version of the LASSI-L (LASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the LASSI-L. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the LASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the LASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil LASSI-L. Overall, the LASSI-BC was comparable, and in some ways, superior to the paper-and-pencil LASSI-L. Advantages of the LASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.

The Association Between Plasma Amyloid-ß 42/40 and Percentage of Semantic Intrusion Errors in Mild Cognitive Impairment.

Background: Semantic intrusion errors (SIEs) are both sensitive and specific to PET amyloid-ß (Aß) burden in older adults with amnestic mild cognitive impairment (aMCI). Objective: Plasma Aß biomarkers including the Aß42/40 ratio using mass spectrometry are expected to become increasingly valuable in clinical settings. Plasma biomarkers are more clinically informative if linked to cognitive deficits that are salient to Alzheimer's disease (AD). Methods: This study included 119 older adults enrolled in the 1Florida Alzheimer's Disease Research Center (ADRC), 45 aMCI participants scored below the established Aß42/40 ratio cut-off of 0.160 using the Quest AD-Detect™ assay indicating Aß positivity (Aß+), while 50 aMCI participants scored above this cut-off indicating Aß negative status (Aß-). Additionally, 24 cognitively unimpaired (CU) persons scored above the cut-off of 0.160 (Aß-). Results: The aMCI plasma Aß+ group evidenced the greatest percentage of SIEs, followed by the aMCI Aß-. The CU Aß- group exhibited the lowest percentage of SIEs. After adjustment for global cognitive impairment, aMCI plasma Aß+ continued to demonstrate greater SIEs on tests tapping the failure to recover from proactive semantic interference (frPSI) as compared to the aMCI Aß-group. Using pre-established cut-offs for frPSI impairment, 8.3% of CU Aß- participants evidenced deficits, compared to 37.8% of aMCI Aß-, and 74.0% of aMCI Aß+. Conclusions: SIEs reflecting frPSI were associated with aMCI Aß+ status based on the Aß42/40 ratio. Results suggest the importance of SIEs as salient cognitive markers that map onto underlying AD pathology in the blood.

Different aspects of failing to recover from proactive semantic interference predicts rate of progression from amnestic mild cognitive impairment to dementia.

Introduction: This study investigated the role of proactive semantic interference (frPSI) in predicting the progression of amnestic Mild Cognitive Impairment (aMCI) to dementia, taking into account various cognitive and biological factors. Methods: The research involved 89 older adults with aMCI who underwent baseline assessments, including amyloid PET and MRI scans, and were followed longitudinally over a period ranging from 12 to 55 months (average 26.05 months). Results: The findings revealed that more than 30% of the participants diagnosed with aMCI progressed to dementia during the observation period. Using Cox Proportional Hazards modeling and adjusting for demographic factors, global cognitive function, hippocampal volume, and amyloid positivity, two distinct aspects of frPSI were identified as significant predictors of a faster decline to dementia. These aspects were fewer correct responses on a frPSI trial and a higher number of semantic intrusion errors on the same trial, with 29.5% and 31.6 % increases in the likelihood of more rapid progression to dementia, respectively. Discussion: These findings after adjustment for demographic and biological markers of Alzheimer's Disease, suggest that assessing frPSI may offer valuable insights into the risk of dementia progression in individuals with aMCI.

Plasma p-tau217 concordance with amyloid PET among ethnically diverse older adults.

INTRODUCTION: Commercially available plasma p-tau217 biomarker tests are not well studied in ethnically diverse samples. METHODS: We evaluated associations between ALZPath plasma p-tau217 and amyloid-beta positron emission tomography (Aß-PET) in Hispanic/Latino (88% of Cuban or South American ancestry) and non-Hispanic/Latino older adults. One- and two-cutoff ranges were derived and evaluated to assess agreement with Aß-PET. RESULTS: A total of 239 participants underwent blood draw and Aß-PET (age 70.8 ± 7.8, 55.2% female, education 15.6 ± 3.4 years, 48.9% Hispanic/Latino, 94.9% white). Plasma p-tau217 showed excellent discrimination of Aß-PET positive and negative participants (visual read: AUC = 0.91 [0.87-0.95], p < 0.001; Centiloids quantification: AUC = 0.90 [0.86-0.94]). There was a greater percent agreement between low p-tau217 and negative Aß-PET (95.8%) than high p-tau217 and positive Aß-PET (86.3%). Analyses within ethnicity-specific subgroups suggested similar p-tau217 performance. DISCUSSION: Plasma p-tau217 (ALZPath) relates to brain Aß in Hispanic/Latino and non-Hispanic/Latino older adults. Independent validation and replication are necessary to establish reference ranges and inform appropriate contexts of use across ethno-racially diverse populations. HIGHLIGHTS: Plasma p-tau217 (ALZPath) and Aß-PET were measured in Hispanic/Latino and non-Hispanic/Latino older adults.Plasma p-tau217 accurately discriminated Aß-PET positive and negative participants.Applying a two-cutoff "intermediate" plasma p-tau217 approach could reduce need for more invasive and costly testing.Plasma p-tau217 associations with Aß-PET were strong within both Hispanic/Latino and non-Hispanic/Latino groups.

A Novel Computerized Cognitive Test for the Detection of Mild Cognitive Impairment and Its Association with Neurodegeneration in Alzheimer's Disease Prone Brain Regions.

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 that are sensitive enough to measure the early brain-behavior manifestations of AD and that correlate with biomarkers of neurodegeneration are needed to identify and monitor individuals at risk for dementia. Weak sensitivity to early cognitive change has been a major limitation of traditional cognitive assessments. In this study, we focused on expanding our previous work by determining whether a digitized cognitive stress test, the Loewenstein-Acevedo Scales for Semantic 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 brain regions. Data was gathered from 111 older adults who were comprehensively evaluated and administered the LASSI-BC. Eighty-seven of these participants (51 CU; 36 aMCI) underwent MR imaging. The volumes of 12 AD-prone brain regions were related to LASSI-BC and other memory tests 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 0.876 (76.1% sensitivity, 82.7% specificity). Further, frPSI on the LASSI-BC was associated with volumetric reductions in the hippocampus, amygdala, inferior temporal lobes, precuneus, and posterior cingulate.

Semantic intrusion errors are associated with plasma Ptau-181 among persons with amnestic mild cognitive impairment who are amyloid positive.

Introduction: Semantic intrusion errors (SI) have distinguished between those with amnestic Mild Cognitive Impairment (aMCI) who are amyloid positive (A+) versus negative (A-) on positron emission tomography (PET). Method: This study examines the association between SI and plasma - based biomarkers. One hundred and twenty-eight participants received SiMoA derived measures of plasma pTau-181, ratio of two amyloid-ß peptide fragments (Aß42/Aß40), Neurofilament Light protein (NfL), Glial Fibrillary Acidic Protein (GFAP), ApoE genotyping, and amyloid PET imaging. Results: The aMCI A+ (n = 42) group had a higher percentage of ApoE ɛ4 carriers, and greater levels of pTau-181 and SI, than Cognitively Unimpaired (CU) A- participants (n = 25). CU controls did not differ from aMCI A- (n = 61) on plasma biomarkers or ApoE genotype. Logistic regression indicated that ApoE ɛ4 positivity, pTau-181, and SI were independent differentiating predictors (Correct classification = 82.0%; Sensitivity = 71.4%; Specificity = 90.2%) in identifying A+ from A- aMCI cases. Discussion: A combination of plasma biomarkers, ApoE positivity and SI had high specificity in identifying A+ from A- aMCI cases.

Persistent Failure to Recover from Proactive Semantic Interference on the Cognitive Stress Test Differentiates Between Amnestic Mild Cognitive Impairment, Pre-Mild Cognitive Impairment, and Cognitively Unimpaired Older Adults.

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.

A Teleneuropsychology Protocol for the Cognitive Assessment of Older Adults During COVID-19.

The Coronavirus Disease 2019 (COVID-19) pandemic prompted the need for a teleneuropsychology protocol for the cognitive assessment of older adults, who are at increased risk for both COVID-19 and dementia. Prior recommendations for teleneuropsychological assessment did not consider many of the unique challenges posed by COVID-19. The field is still in need of clear guidelines and standards of care for the assessment of older adults under the current circumstances. Advantages of teleneuropsychological assessment during the COVID-19 pandemic include reduced risk of contracting the virus, eliminating travel time and reducing cost, and more rapid access to needed services. Challenges include disparities in technology access among patients, reduced control over the testing environment, impeded ability to make behavioral observations, and limited research on valid and reliable cognitive assessment measures. The aim of this perspective review is to propose a teleneuropsychological protocol to facilitate neuropsychological assessment utilizing a virtual platform. The proposed protocol has been successful with our clinical and research populations and may help neuropsychologists implement teleneuropsychology services without compromising validity or reliability. However, there is increasing need for research on teleneuropsychological assessment options for both clinical and research purposes.

The relationship of semantic intrusions to different etiological subtypes of MCI and cognitively healthy older adults.

INTRODUCTION: There is increasing evidence that susceptibility to proactive semantic interference (PSI) and the failure to recover from PSI (frPSI) as evidenced by intrusion errors may be early cognitive markers of both preclinical and prodromal Alzheimer's disease (AD). METHODS: One hundred forty-five participants were administered extensive clinical and neuropsychological evaluations including the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), a sensitive cognitive stress test measuring PSI and frPSI. Participants also underwent structural magnetic resonance imaging (MRI) and amyloid positron emission tomography/computed tomography (PET/CT) imaging. RESULTS: PSI and frPSI errors were much more prevalent in the mild cognitive impairment (MCI)-AD (amyloid positive) group than the other diagnostic groups. The number of intrusion errors observed across the other MCI groups without amyloid pathology and those with normal cognition were comparable. DISCUSSION: Semantic intrusion errors on the LASSI-L occur much less frequently in persons who have different types of non-AD-related MCI and may be used as an early cognitive marker of prodromal AD.

Changes in LASSI-L performance over time among older adults with amnestic MCI and amyloid positivity: A preliminary study.

There is a pressing need to develop measures that are sensitive to the earliest subtle cognitive changes of Alzheimer's disease (AD) to improve early detection and track disease progression. The Loewenstein-Acevedo Scales of Semantic Interference (LASSI-L) has been shown to successfully discriminate between cognitively unimpaired (CU) older adults and those with amnestic mild cognitive impairment (MCI) and to correlate with total and regional brain amyloid load. The present study investigated how the LASSI-L scores change over time among three distinct diagnostic groups. Eighty-six community-dwelling older adults underwent a baseline evaluation including: a clinical interview, a neuropsychological evaluation, Magnetic Resonance Imaging (MRI), and amyloid Positron Emission Tomography (PET). A follow up evaluation was conducted 12 months later. Initial mean values were calculated using one-way ANOVAs and chi-square analyses. Post-hoc comparisons were conducted using Tukey's Honestly Significant Difference (HSD). A 3 × 2 repeated measures analysis was utilized to examine differences in LASSI-L performance over time. The MCI amyloid positive group demonstrated a significantly greater decline in LASSI-L performance than the MCI amyloid negative and CU groups respectively. The scales that best differentiated the three groups included the Cued A2, which taps into maximum learning capacity, and Cued B2, which assesses the failure to recover from proactive semantic interference. Our findings further support the LASSI-L's discriminative validity.

How late-life depression affects cognition: neural mechanisms.

Late-life depression is a major health problem and a significant cause of dysfunction that warrants closer evaluation and study. In contrast to younger depressed patients, most depressed older adults suffer more severe variants of the disorder, including significant cognitive impairments. These cognitive changes add to the severity of symptoms and disability that older depressed patients face and likely reflect compromise of certain neural circuits, linking cognitive impairment to late-life depression. Studies examining clinical correlates, neuropsychological testing, and functional and anatomic imaging have yielded a clearer understanding of the neural mechanisms underlying cognitive deficits in late-life depression. This article discusses cognitive impairment in geriatric depression and how developing a better understanding of its neural correlates may lead to improved understanding and outcome of this specific disorder.

A Brief Version of the LASSI-L Detects Prodromal Alzheimer's Disease States.

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.

Semantic Intrusion Error Ratio Distinguishes Between Cognitively Impaired and Cognitively Intact African American Older Adults.

BACKGROUND: Semantic intrusion errors on memory tests may represent very early cognitive changes associated with elevated Alzheimer's disease pathology within the brain, including amyloid-ß (Aß). Subscales that measure proactive semantic interference (PSI) and intrusions related to PSI on the Loewenstein Acevedo Scales of Semantic Interference and Learning (LASSI-L) have been associated with high levels of brain amyloid load, structural changes on brain MRI in Hispanic and non-Hispanic groups. It is presently unknown whether intrusion errors or other measures of the LASSI-L can differentiate between African-American (AA) older adults diagnosed with amnestic mild cognitive impairment (aMCI) or classified as cognitively normal (CN). OBJECTIVE: This study examined the extent to which a high percentage of semantic intrusion errors on LASSI-L subscales susceptible to PSI and other LASSI-L measures could differentiate between AA aMCI and CN groups. METHODS: Forty-eight AA older adults were recruited (27 CN and 21 aMCI) and received a through clinical and neuropsychological evaluation. The LASSI-L was administered independent of diagnostic classification. RESULTS: With and without statistical adjustment for literacy, AA aMCI participants scored lower on all LASSI-L measures. ROC analyses revealed an area under the curve exceeding 90% and correctly classified 86% of AA aMCI with 82% specificity for AA CN participants. CONCLUSIONS: Percentage of intrusion errors on the LASSI-L subscales susceptible to PSI differentiated AA aMCI from AA CN. This adds to emerging evidence indicating that the LASSI-L may be culturally appropriate and can differentiate between aMCI and CN in diverse ethnic/cultural groups.