Diffusion MRI relates to plasma Aß42/40 in PET negative participants without dementia.

INTRODUCTION: Magnetic resonance imaging (MRI) biomarkers are needed for indexing early biological stages of Alzheimer's disease (AD), such as plasma amyloid-ß (Aß42/40) positivity in Aß positron emission tomography (PET) negative individuals. METHODS: Diffusion free-water (FW) MRI was acquired in individuals with normal cognition (NC) and mild cognitive impairment (MCI) with Aß plasma-/PET- (NC = 22, MCI = 60), plasma+/PET- (NC = 5, MCI = 20), and plasma+/PET+ (AD dementia = 21) biomarker status. Gray and white matter FW and fractional anisotropy (FAt) were compared cross-sectionally and the relationships between imaging, plasma and PET biomarkers were assessed. RESULTS: Plasma+/PET- demonstrated increased FW (24 regions) and decreased FAt (66 regions) compared to plasma-/PET-. FW (16 regions) and FAt (51 regions) were increased in plasma+/PET+ compared to plasma+/PET-. Composite brain FW correlated with plasma Aß42/40 and p-tau181. DISCUSSION: FW imaging changes distinguish plasma Aß42/40 positive and negative groups, independent of group differences in cognitive status, Aß PET status, and other plasma biomarkers (i.e., t-tau, p-tau181, glial fibrillary acidic protein, neurofilament light). HIGHLIGHTS: Plasma Aß42/40 positivity is associated with brain microstructure decline. Plasma+/PET- demonstrated increased FW in 24 total GM and WM regions. Plasma+/PET- demonstrated decreased FAt in 66 total GM and WM regions. Whole-brain FW correlated with plasma Aß42/40 and p-tau181 measures. Plasma+/PET- demonstrated decreased cortical volume and thickness.

Plasma Alzheimer's biomarkers and brain amyloid in Hispanic and non-Hispanic older adults.

INTRODUCTION: Alzheimer's disease studies often lack ethnic diversity. METHODS: We evaluated associations between plasma biomarkers commonly studied in Alzheimer's (p-tau181, GFAP, and NfL), clinical diagnosis (clinically normal, amnestic MCI, amnestic dementia, or non-amnestic MCI/dementia), and Aß-PET in Hispanic and non-Hispanic older adults. Hispanics were predominantly of Cuban or South American ancestry. RESULTS: Three-hundred seventy nine participants underwent blood draw (71.9 ± 7.8 years old, 60.2% female, 57% Hispanic of which 88% were Cuban or South American) and 240 completed Aß-PET. P-tau181 was higher in amnestic MCI (p = 0.004, d = 0.53) and dementia (p < 0.001, d = 0.97) than in clinically normal participants and discriminated Aß-PET[+] and Aß-PET[-] (AUC = 0.86). P-tau181 outperformed GFAP and NfL. There were no significant interactions with ethnicity. Among amnestic MCI, Hispanics had lower odds of elevated p-tau181 than non-Hispanic (OR = 0.41, p = 0.006). DISCUSSION: Plasma p-tau181 informs etiological diagnosis of cognitively impaired Hispanic and non-Hispanic older adults. Hispanic ethnicity may relate to greater likelihood of non-Alzheimer's contributions to memory loss. HIGHLIGHTS: Alzheimer's biomarkers were measured in Hispanic and non-Hispanic older adults. Plasma p-tau181 related to amnestic cognitive decline and brain amyloid burden. AD biomarker associations did not differ between Hispanic and non-Hispanic ethnicity. Hispanic individuals may be more likely to have non-Alzheimer causes of memory loss.

Poor sleep accelerates hippocampal and posterior cingulate volume loss in cognitively normal healthy older adults.

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 score <5) 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.

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.

Feasibility and Preliminary Efficacy of a Multimodal Approach to Increase Physical Activity in Older Adults With Memory Complaints: The Education for Action Study.

In this randomized controlled pilot trial, the authors explored the feasibility, technology compliance, and preliminary efficacy of the Education for Action (EDU-ACT), a multimodal intervention combining evidence-based strategies of physical activity (PA) education and coaching in PA levels over 4 weeks between EDU-ACT and control groups. The authors also assessed pre-post changes in neurocognitive function, functional mobility and dual-task performance, sleep and quality of life. Thirty-two sedentary older adults with memory complaints (age = 66 ± 5.3) completed the study (EDU-ACT = 18 and control = 14). The EDU-ACT adherence rate was 95%, and compliance of daily PA reporting was, on average, 22.7 days (94.6%). The EDU-ACT group demonstrated a significantly greater number of steps, processing speed, and dual-task performance when compared with controls (p < .05). In this study, a multimodal, evidence-based, low-cost intervention was feasible, well-accepted, with high adherence and compliance rates, and effective at promoting clinically meaningful increases in PA, for at least 1 month postintervention, in older adults with memory complaints.

Associations Between Country where Education is Obtained and Cognitive Functioning Among South American and Caribbean Older Adults Living in the U.S.

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.

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.

Mild behavioral impairment as a predictor of cognitive functioning in older adults.

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.

Neuropsychiatric symptoms as a distinguishing factor between memory diagnoses.

OBJECTIVES: To determine whether neuropsychiatric symptoms (NPS) are able to differentiate those with mild cognitive impairment (MCI) and dementia from persons who are cognitively healthy. METHODS: Multinomial and binary logistic regressions were used to assess secondary data of a sample (n = 613) of older adults with NPS. Analyses evaluated the ability to differentiate between diagnoses, as well as the influence of these symptoms for individuals with amnestic MCI (MCI-A), non-amnestic MCI (MCI-NA), and dementia compared with those who are cognitively healthy. RESULTS: Persons with MCI were more likely to have anxiety, apathy, and appetite changes compared with cognitively healthy individuals. Persons with dementia were more likely to have aberrant motor behaviors, anxiety, apathy, appetite changes, and delusions compared with those who were cognitively healthy. Individuals with any type of cognitive impairment were more likely to have anxiety, apathy, appetite changes, and delusions. Specifically, anxiety, apathy, appetite changes, and disinhibition were predictors of MCI-A; agitation and apathy were predictors of MCI-NA; and aberrant motor behaviors, anxiety, apathy, appetite changes, and delusions were predictors of dementia. Finally, nighttime behavior disorders were less likely in individuals with dementia. CONCLUSIONS: The present study's results demonstrate that specific NPS are differentially represented among types of cognitive impairment and establish the predictive value for one of these cognitive impairment diagnoses.

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).

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).

A clinically-translatable machine learning algorithm for the prediction of Alzheimer's disease conversion: further evidence of its accuracy via a transfer learning approach.

BACKGROUND: In a previous study, we developed a highly performant and clinically-translatable machine learning algorithm for a prediction of three-year conversion to Alzheimer's disease (AD) in subjects with Mild Cognitive Impairment (MCI) and Pre-mild Cognitive Impairment. Further tests are necessary to demonstrate its accuracy when applied to subjects not used in the original training process. In this study, we aimed to provide preliminary evidence of this via a transfer learning approach. METHODS: We initially employed the same baseline information (i.e. clinical and neuropsychological test scores, cardiovascular risk indexes, and a visual rating scale for brain atrophy) and the same machine learning technique (support vector machine with radial-basis function kernel) used in our previous study to retrain the algorithm to discriminate between participants with AD (n = 75) and normal cognition (n = 197). Then, the algorithm was applied to perform the original task of predicting the three-year conversion to AD in the sample of 61 MCI subjects that we used in the previous study. RESULTS: Even after the retraining, the algorithm demonstrated a significant predictive performance in the MCI sample (AUC = 0.821, 95% CI bootstrap = 0.705-0.912, best balanced accuracy = 0.779, sensitivity = 0.852, specificity = 0.706). CONCLUSIONS: These results provide a first indirect evidence that our original algorithm can also perform relevant generalized predictions when applied to new MCI individuals. This motivates future efforts to bring the algorithm to sufficient levels of optimization and trustworthiness that will allow its application in both clinical and research settings.

Relationship between Cognitive Performance and Measures of Neurodegeneration among Hispanic and White Non-Hispanic Individuals with Normal Cognition, Mild Cognitive Impairment, and Dementia.

OBJECTIVES: The aim of this study was to determine the presence and severity of potential cultural and language bias in widely used cognitive and other assessment instruments, using structural MRI measures of neurodegeneration as biomarkers of disease stage and severity. METHODS: Hispanic (n=75) and White non-Hispanic (WNH) (n=90) subjects were classified as cognitively normal (CN), amnestic mild cognitive impairment (aMCI) and mild dementia. Performance on the culture-fair and educationally fair Fuld Object Memory Evaluation (FOME) and Clinical Dementia Rating Scale (CDR) between Hispanics and WNHs was equivalent, in each diagnostic group. Volumetric and visually rated measures of the hippocampus entorhinal cortex, and inferior lateral ventricles (ILV) were measured on structural MRI scans for all subjects. A series of analyses of covariance, controlling for age, depression, and education, were conducted to compare the level of neurodegeneration on these MRI measures between Hispanics and WNHs in each diagnostic group. RESULTS: Among both Hispanics and WNH groups there was a progressive decrease in volume of the hippocampus and entorhinal cortex, and an increase in volume of the ILV (indicating increasing atrophy in the regions surrounding the ILV) from CN to aMCI to mild dementia. For equivalent levels of performance on the FOME and CDR, WNHs had greater levels of neurodegeneration than did Hispanic subjects. CONCLUSIONS: Atrophy in medial temporal regions was found to be greater among WNH than Hispanic diagnostic groups, despite the lack of statistical differences in cognitive performance between these two ethnic groups. Presumably, unmeasured factors result in better cognitive performance among WNH than Hispanics for a given level of neurodegeneration. (JINS, 2018, 24, 176-187).

Does a cognitive stress test predict progression from mild cognitive impairment to dementia equally well in clinical versus population-based settings?

ABSTRACTBackground:Evidence suggests that semantic interference may be a sensitive indicator of early dementia. We examined the utility of the Semantic Interference Test (SIT), a cognitive stress memory paradigm which taps proactive and retroactive semantic interference, for predicting progression from mild cognitive impairment (MCI) to dementia in both a clinical and a population-based sample. METHODS: Participants with MCI in the clinical (n = 184) and population-based (n = 435) samples were followed for up to four years. We employed receiver operating characteristic (ROC) methods to establish optimal thresholds for four different SIT indices. Threshold performance was compared in the two samples using logistic and Cox proportional hazard regression models. RESULTS: Within four years, 42 (22.8%) MCI individuals in the clinical sample and 45 (10.3%) individuals in the population-based sample progressed to dementia. Overall classification accuracy of SIT thresholds ranged from 61.4% to 84.8%. Different subtests of the SIT had slightly different performance characteristics in the two samples. However, regression models showed that thresholds established in the clinical sample performed similarly in the population sample before and after adjusting for demographics and other baseline neuropsychological test scores. CONCLUSIONS: Despite differences in demographic composition and progression rates, baseline SIT scores predicted progression from MCI to dementia similarly in both samples. Thresholds that best predicted progression were slightly below thresholds established for distinguishing between amnestic MCI and cognitively normal subjects in clinical practice. This confirms the utility of the SIT in both clinical and population-based samples and establishes thresholds most predictive of progression of individuals with MCI.

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.

Proactive Semantic Interference is Associated with Total and Regional Abnormal Amyloid Load in Non-Demented Community-Dwelling Elders: A Preliminary Study.

OBJECTIVE: To evaluate the relationship between susceptibility to proactive semantic interference (PSI) and retroactive semantic interference (RSI) and brain amyloid load in non-demented elders. METHODS: 27 participants (11 cognitively normal [CN] with subjective memory complaints, 8 CN without memory complaints, and 8 with mild cognitive impairment [MCI]) underwent complete neurological and neuropsychological evaluations. Participants also received the Semantic Interference Test (SIT) and AV-45 amyloid PET imaging. RESULTS: High levels of association were present between total amyloid load, regional amyloid levels, and the PSI measure (in the entire sample and a subsample excluding MCI subjects). RSI and other memory measures showed much weaker associations or no associations with total and regional amyloid load. No associations between amyloid levels and non-memory performance were observed. CONCLUSIONS: In non-demented individuals, vulnerability to PSI was highly associated with total and regional beta-amyloid load and may be an early cognitive marker of brain pathology.

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.

Verbal fluency patterns in mild cognitive impairment and Alzheimer's disease.

BACKGROUND/AIMS: Verbal fluency patterns can assist in differential diagnosis during neuropsychological assessment and identify individuals at risk for developing Alzheimer's disease (AD). While evidence suggests that subjects with AD perform worse on category fluency than letter fluency tasks, the pattern in mild cognitive impairment (MCI) is less well known. METHODS: Performance on the Controlled Oral Word Association Test (COWAT) and Animal fluency was compared in control, amnestic MCI, non-amnestic MCI, and AD groups. The sample included 136 participants matched for age, education, and gender. RESULTS: Both MCI groups performed similarly with a category > letter fluency pattern rather than a category < letter fluency pattern typically observed in AD. The pattern in MCI, albeit relatively more impaired than in controls, was more similar to healthy controls who exhibited a category > letter fluency pattern. CONCLUSION: MCI using a category < letter fluency pattern may not represent AD; however, future research requires longitudinal studies of pattern analysis.

Vascular risk factors and cognitive decline in a population sample.

We examined several vascular factors in relation to the rates of decline in 5 cognitive domains in a population-based cohort. In an age-stratified random sample (N=1982) aged 65+ years, we assessed at baseline the cognitive domains of attention, executive function, memory, language, and visuospatial function, and also vascular, inflammatory, and metabolic indices. Random effects models generated slopes of cognitive decline over the next 4 years; linear models identified vascular factors associated with these slopes, adjusting for demographics, baseline cognition, and potential interactions. Several vascular risk factors (history of stroke, diabetes, central obesity, C-reactive protein), although associated with lower baseline cognitive performance, did not predict rate of subsequent decline. APOE*4 genotype was associated with accelerated decline in language, memory, and executive functions. Homocysteine elevation was associated with faster decline in executive function. Hypertension (history or systolic blood pressure >140 mm Hg) was associated with slower decline in memory. Baseline alcohol consumption was associated with slower decline in attention, language, and memory. Different indices of vascular risk are associated with low performance and with rates of decline in different cognitive domains. Cardiovascular mechanisms explain at least some of the variance in cognitive decline. Selective survival may also play a role.

Free-water imaging reveals unique brain microstructural deficits in hispanic individuals with Dementia.

Prior evidence suggests that Hispanic and non-Hispanic individuals differ in potential risk factors for the development of dementia. Here we determine whether specific brain regions are associated with cognitive performance for either ethnicity along various stages of Alzheimer's disease. For this cross-sectional study, we examined 108 participants (61 Hispanic vs. 47 Non-Hispanic individuals) from the 1Florida Alzheimer's Disease Research Center (1Florida ADRC), who were evaluated at baseline with diffusion-weighted and T1-weighted imaging, and positron emission tomography (PET) amyloid imaging. We used FreeSurfer to segment 34 cortical regions of interest. Baseline Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used as measures of cognitive performance. Group analyses assessed free-water measures (FW) and volume. Statistically significant FW regions based on ethnicity x group interactions were used in a stepwise regression function to predict total MMSE and MoCA scores. Random forest models were used to identify the most predictive brain-based measures of a dementia diagnosis separately for Hispanic and non-Hispanic groups. Results indicated elevated FW values for the left inferior temporal gyrus, left middle temporal gyrus, left banks of the superior temporal sulcus, left supramarginal gyrus, right amygdala, and right entorhinal cortex in Hispanic AD subjects compared to non-Hispanic AD subjects. These alterations occurred in the absence of different volumes of these regions in the two AD groups. FW may be useful in detecting individual differences potentially reflective of varying etiology that can influence cognitive decline and identify MRI predictors of cognitive performance, particularly among Hispanics.