An enhanced delayed recognition measure for the Logical Memory subtest of the Wechsler Memory Scale - IV.

We provide a supplemental measure based on the Logical Memory (LM) subtest of the Wechsler Memory Scale - IV (Wechsler, 2008) to assist in distinguishing deficient memory storage from compromised retrieval operations. A 20-item five-option multiple choice delayed recognition test for the LM stories is described, followed by descriptive data based on a normative sample of 273 neuropsychologically normal outpatient referrals to a neuropsychology clinic. The analysis indicated that about 43% to 48% of the neuropsychology referrals exhibited retrieval difficulties and were able to store more information in long-term memory than they were able to retrieve on the delayed free recall trial. The 20-item measure, freely available to qualified clinicians, provides useful information regarding a person's ability to store and access newly acquired information.

The Cognitive Difficulties Scale (CDS): Psychometric Characteristics in a Clinical Referral Sample.

OBJECTIVE: To evaluate the psychometric characteristics of the Cognitive Difficulties Scale (CDS), a 39-item Likert-type self-report instrument that requires a fifth grade reading level. The CDS is a popular instrument that has been shown to predict cognitive decline in older persons. METHOD: Participants were 512 consecutive outpatient referrals (71% women, mean age 60.6, and education 14.6 years) for a neuropsychological examination in a memory disorders clinic as part of a broader neurodiagnostic workup for cognitive decline. A principal components analysis was followed by a varimax rotation (Kaiser). Factor scores were investigated in relation to multiple internal and external criteria including demographics, Cronbach's alpha, Digit Span, and Wechsler Memory Scale-IV Logical Memory (LM) and Visual Reproduction (VR), and Minnesota Multiphasic Personality Inventory (MMPI)-2 measures of depression, anxiety, somatic preoccupations, and thought disturbance. RESULTS: Six dimensions of cognitive complaint emerged accounting for 64% of the variance: attention/concentration, praxis, prospective memory, speech problems, memory for people's names, and temporal orientation. The factors showed good internal consistency (alphas > .850). Correlations with Digit Span, LM, and VR were all nonsignificant. CDS scores were associated with MMPI-2 measures of anxiety, depression, somatic preoccupation, and thought disturbance. Percentiles and T-scores were derived for raw scores on the CDS and its six component subscales. CONCLUSION: The CDS is a multidimensional measure of subjective cognitive complaints that provides clinicians with a psychometrically sound basis for deriving a profile with six subscale scores. The test has clinical utility and is a potentially useful tool in research involving age-related cognitive changes and meta-cognition.

A cognitive stress test for prodromal Alzheimer's disease: Multiethnic generalizability.

INTRODUCTION: Culturally fair cognitive assessments sensitive to detecting changes associated with prodromal Alzheimer's disease are needed. METHODS: Performance of Hispanic and non-Hispanic older adults on the Loewenstein-Acevedo Scale of Semantic Interference and Learning (LASSI-L) was examined in persons with amnestic mild cognitive impairment (aMCI) or normal cognition. The association between a novel cognitive marker, the failure to recover from proactive semantic interference (frPSI), and cortical thinning was explored. RESULTS: English-speaking aMCI participants scored lower than cognitively normal participants on all LASSI-L indices, while Spanish-speaking aMCI participants scored lower in learning, frPSI, and delayed recall. Healthy controls obtained equivalent scores on all indices except retroactive semantic interference. English-speaking and Spanish-speaking aMCI participants had equivalent scores except English speaker's greater vulnerability to frPSI. Across aMCI groups, frPSI was associated with cortical thinning of the entorhinal cortex and precuneus (r = -0.45 to r = 0.52; P < .005). DISCUSSION: In diverse populations, LASSI-L performance differentiated patients with aMCI from cognitively normal older adults and was associated with thinning in Alzheimer's disease-prone regions, suggesting its clinical utility.

Visual Object Discrimination Impairment as an Early Predictor of Mild Cognitive Impairment and Alzheimer's Disease.

OBJECTIVE: Detection of cognitive impairment suggestive of risk for Alzheimer's disease (AD) progression is crucial to the prevention of incipient dementia. This study was performed to determine if performance on a novel object discrimination task improved identification of earlier deficits in older adults at risk for AD. METHOD: In total, 135 participants from the 1Florida Alzheimer's Disease Research Center [cognitively normal (CN), Pre-mild cognitive impairment (PreMCI), amnestic mild cognitive impairment (aMCI), and dementia] completed a test of object discrimination and traditional memory measures in the context of a larger neuropsychological and clinical evaluation. RESULTS: The Object Recognition and Discrimination Task (ORDT) revealed significant differences between the PreMCI, aMCI, and dementia groups versus CN individuals. Moreover, relative risk of being classified as PreMCI rather than CN increased as an inverse function of ORDT score. DISCUSSION: Overall, the obtained results suggest that a novel object discrimination task improves the detection of very early AD-related cognitive impairment, increasing the window for therapeutic intervention. (JINS, 2019, 25, 688-698).

Types of errors on a semantic interference task in mild cognitive impairment and dementia.

OBJECTIVE: This research aimed to determine whether qualitative analysis of different types of intrusion errors on a verbal cognitive task was useful in detecting subtle cognitive impairment in preclinical stages prior to the progression to dementia. METHOD: Different types of semantic intrusions on the Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L) were compared across 160 individuals diagnosed as cognitively normal (CN), amnestic Mild Cognitive Impairment (aMCI), and dementia. The sample included Hispanics and non-Hispanic European Americans. RESULTS: Across diagnostic groups, the most common type of intrusion error was actual targets presented from a competing word list under conditions eliciting proactive semantic interference (PSI), and retroactive semantic interference (RSI), followed by intrusions that represented one of three overlapping semantic categories but none of the targets from List A or B. Nonsemantic intrusions rarely occurred. These competing list intrusions (CLI) and semantically related intrusions (SRI) differentiated between aMCI and CN participants. Further, these intrusion error were related to brain amyloid load, indicating their importance as potential primary markers of AD-related neurodegeneration. Ethnicity effects were not seen across the types of intrusion errors. CONCLUSIONS: Two types of intrusion errors (CLI and SRI) showed differences between the CN and aMCI group, with the aMCI group evidencing a higher rate of these intrusion errors compared with the CN group. These results support previous literature about the LASSI-L's sensitivity at the earliest stages of abnormal aging. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Effects of Bilingualism on Verbal and Nonverbal Memory Measures in Mild Cognitive Impairment.

OBJECTIVES: Maintaining two active languages may increase cognitive and brain reserve among bilingual individuals. We explored whether such a neuroprotective effect was manifested in the performance of memory tests for participants with amnestic mild cognitive impairment (aMCI). METHODS: We compared 42 bilinguals to 25 monolinguals on verbal and nonverbal memory tests. We used: (a) the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), a sensitive test that taps into proactive, retroactive, and recovery from proactive semantic interference (verbal memory), and (b) the Benson Figure delayed recall (nonverbal memory). A subsample had volumetric MRI scans. RESULTS: The bilingual group significantly outperformed the monolingual group on two LASSI-L cued recall measures (Cued A2 and Cued B2). A measure of maximum learning (Cued A2) showed a correlation with the volume of the left hippocampus in the bilingual group only. Cued B2 recall (sensitive to recovery from proactive semantic interference) was correlated with the volume of the hippocampus and the entorhinal cortex of both cerebral hemispheres in the bilingual group, as well as with the left and right hippocampus in the monolingual group. The memory advantage in bilinguals on these measures was associated with higher inhibitory control as measured by the Stroop Color-Word test. CONCLUSIONS: Our results demonstrated a superior performance of aMCI bilinguals over aMCI monolinguals on selected verbal memory tasks. This advantage was not observed in nonverbal memory. Superior memory performance of bilinguals over monolinguals suggests that bilinguals develop a different and perhaps more efficient semantic association system that influences verbal recall. (JINS, 2019, 25, 15-28).

Utilizing semantic intrusions to identify amyloid positivity in mild cognitive impairment.

OBJECTIVE: Semantic intrusion (SI) errors may highlight specific breakdowns in memory associated with preclinical Alzheimer disease (AD); however, there have been no investigations to determine whether SI errors occur with greater frequency in persons with amnestic mild cognitive impairment (aMCI) confirmed as amyloid positive (Amy+) vs those who have clinical symptoms of aMCI-AD with negative amyloid scans (suspected non-AD pathology [SNAP]) or persons who are diagnosed with other brain disorders affecting cognition. METHODS: Eighty-eight participants with aMCI underwent brain amyloid PET and MRI scans and were classified as early AD (Amy+), SNAP (Amy-), or other neurological/psychiatric diagnosis (Amy-). We focused on SI on the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) targeting proactive semantic interference (PSI; old semantic learning interferes with new semantic learning), failure to recover from PSI after an additional learning trial (frPSI), and retroactive semantic interference (new semantic learning interferes with memory for old semantic learning). RESULTS: SIs on measures of PSI and frPSI distinguished between Amy+ AD and SNAP and other non-AD cases. PSI and frPSI intrusions evidenced moderately high associations with reduced volumes in the entorhinal cortex, superior temporal regions, and supramarginal gyrus. No such associations were observed in cases with SNAP. CONCLUSIONS: SIs on the LASSI-L related to PSI and frPSI uniquely differentiated Amy+ and Amy- participants with aMCI and likely reflect deficits with inhibition and source memory in preclinical AD not captured by traditional cognitive measures. This may represent a specific, noninvasive test successful at distinguishing cases with true AD from those with SNAP.

Semantic Intrusions and Failure to Recover From Semantic Interference in Mild Cognitive Impairment: Relationship to Amyloid and Cortical Thickness.

BACKGROUND: Accumulating evidence indicates that the failure to recover from the effects of proactive semantic interference [frPSI] represents an early cognitive manifestation of preclinical Alzheimer's disease. A limitation of this novel paradigm has been a singular focus on the number of targets correctly recalled, without examining co-occurring semantic intrusions [SI] that may highlight specific breakdowns in memory. OBJECTIVES: We focused on SI and their relationship to amyloid load and regional cortical thickness among persons with amnestic mild cognitive impairment (aMCI). METHODS: Thirty-three elders diagnosed with aMCI underwent F-18 florbetaben amyloid PET scanning with MRI scans of the brain. We measured the correlation of SI elicited on cued recall trials of the Loewenstein-Acevedo Scales for Semantic Interference and Learning [LASSI-L] with mean cortical amyloid load and regional cortical thickness in AD prone regions. RESULTS: SI on measures sensitive to frPSI was related to greater total amyloid load and lower overall cortical thickness [CTh]. In particular, SI were highly associated with reduced CTh in the left entorhinal cortex [r=-.71; p<.001] and left medial orbital frontal lobe [r=-.64; p<.001]; together accounting for 66% of the explained variability in regression models. CONCLUSION: Semantic intrusions on measures susceptible to frPSI related to greater brain amyloid load and lower cortical thickness. These findings further support the hypothesis that frPSI, as expressed by the percentage of intrusions, may be a cognitive marker of initial neurodegeneration and may serve as an early and distinguishing test for preclinical AD that may be used in primary care or clinical trial settings.

A novel cognitive assessment paradigm to detect Pre-mild cognitive impairment (PreMCI) and the relationship to biological markers of Alzheimer's disease.

OBJECTIVE: A number of older adults obtain normal scores on formal cognitive tests, but present clinical concerns that raise suspicion of cognitive decline. Despite not meeting full criteria for Mild Cognitive Impairment (MCI), these PreMCI states confer risk for progression to Alzheimer's disease (AD). This investigation addressed a pressing need to identify cognitive measures that are sensitive to PreMCI and are associated with brain biomarkers of neurodegeneration. METHOD: Participants included 49 older adults with a clinical history suggestive of cognitive decline but normal scores on an array of neuropsychological measures, thus not meeting formal criteria for MCI. The performance of these PreMCI participants were compared to 117 cognitively normal (CN) elders on the LASSI-L, a cognitive stress test that uniquely assesses the failure to recover from proactive semantic interference effects (frPSI). Finally, a subset of these individuals had volumetric analyses based on MRI scans. RESULTS: PreMCI participants evidenced greater LASSI- L deficits, particularly with regards to frPSI and delayed recall, relative to the CN group. No differences on MRI measures were observed. Controlling for false discovery rate (FDR), frPSI was uniquely related to increased dilatation of the inferior lateral ventricle and decreased MRI volumes in the hippocampus, precuneus, superior parietal region, and other AD prone areas. In contrast, other LASSI-L indices and standard memory tests were not related to volumetric findings. CONCLUSIONS: Despite equivalent performance on traditional memory measures, the frPSI distinguished between PreMCI and CN elders and was associated with reductions in brain volume in numerous AD-relevant brain regions.

Recovery from Proactive Semantic Interference and MRI Volume: A Replication and Extension Study.

BACKGROUND: The rise in incidence of Alzheimer's disease (AD) has led to efforts to advance early detection of the disease during its preclinical stages. To achieve this, the field needs to develop more sensitive cognitive tests that relate to biological markers of disease pathology. Failure to recover from proactive interference (frPSI) is one such cognitive marker that is associated with volumetric reductions in the hippocampus, precuneus, and other AD-prone regions, and to amyloid load in the brain. OBJECTIVE: The current study attempted to replicate and extend our previous findings that frPSI is a sensitive marker of early AD, and related to a unique pattern of volumetric loss in AD prone areas. METHODS: Three different memory measures were examined relative to volumetric loss and cortical thickness among 45 participants with amnestic mild cognitive impairment. RESULTS: frPSI was uniquely associated with reduced volumes in the hippocampus (r = 0.50) precuneus (r = 0.41), and other AD prone regions, replicating previous findings. Strong associations between frPSI and lower entorhinal cortex volumes and cortical thickness (r≥0.60) and precuneus (r = 0.50) were also observed. CONCLUSION: Unique and strong associations between volumetric reductions and frPSI as observed by Loewenstein and colleagues were replicated. Together with cortical thickness findings, these results indicate that frPSI is worthy of further study as a sensitive and early cognitive marker of AD.

Recovery from Proactive Semantic Interference in Mild Cognitive Impairment and Normal Aging: Relationship to Atrophy in Brain Regions Vulnerable to Alzheimer's Disease.

BACKGROUND: There is growing evidence that proactive semantic interference (PSI) and failure to recover from PSI may represent early features of Alzheimer's disease (AD). OBJECTIVE: This study investigated the association between PSI, recovery from PSI, and reduced MRI volumes in AD signature regions among cognitively impaired and unimpaired older adults. METHODS: Performance on the LASSI-L (a novel test of PSI and recovery from PSI) and regional brain volumetric measures were compared between 38 cognitively normal (CN) elders and 29 older participants with amnestic mild cognitive impairment (MCI). The relationship between MRI measures and performance on the LASSI-L as well as traditional memory and non-memory cognitive measures was also evaluated in both diagnostic groups. RESULTS: Relative to traditional neuropsychological measures, MCI patients' failure to recover from PSI was associated with reduced volumes in the hippocampus (rs = 0.48), precuneus (rs = 0.50); rostral middle frontal lobules (rs = 0.54); inferior temporal lobules (rs = 0.49), superior parietal lobules (rs = 0.47), temporal pole (rs = 0.44), and increased dilatation of the inferior lateral ventricle (rs = -0.49). For CN elders, only increased inferior lateral ventricular size was associated with vulnerability to PSI (rs = -0.49), the failure to recover from PSI (rs = -0.57), and delayed recall on the Hopkins Verbal Learning Test-Revised (rs = -0.48). DISCUSSION: LASSI-L indices eliciting failure to recover from PSI were more highly associated with more MRI regional biomarkers of AD than other traditional cognitive measures. These results as well as recent amyloid imaging studies with otherwise cognitively normal subjects, suggest that recovery from PSI may be a sensitive marker of preclinical AD and deserves further investigation.