Search

Objective: Medial temporal lobe atrophy (MTA) can be used as a biomarker of pathology that affects mechanisms of episodic memory. The authors compared the strength of this biomarker with performance on four memory measures and examined the influence of demographic factors including age, level of education, and primary language (English or Spanish).Methods: The Hopkins Verbal Learning Test-revised, Fuld Object Memory Evaluation (FOME), delayed memory for a story passage, and delayed visual reproduction of the Wechsler Memory Scale-revised tests were administered to 281 subjects who were diagnosed as having no cognitive impairment, mild cognitive impairment (MCI), impaired non-MCI, or dementia. MTA scores were obtained from visual ratings of the hippocampus, entorhinal cortex, and perirhinal cortex on coronal magnetic resonance imaging scans using a magnetization-prepared rapid gradient echo protocol.Results: Age was associated with scores on all memory measures and MTA. Level of educational attainment had no influence on FOME performance but had greater associations with scores on other memory measures. In regression models, FOME scores had the strongest relationship with MTA scores, accounting for 31% of the explained variability. Among subjects with MCI, an index representing the total number of memory tests that were impaired was also predictive of the severity of MTA scores.Conclusion: Among four common tests of memory, the FOME was highly associated with MTA, and it exhibited minimal influences of education. Impairment on more than one memory test was more predictive of MTA than impairment on a single memory test. [ABSTRACT FROM AUTHOR]

There has been increasing interest in determining whether amnestic, nonamnestic and multiple-domain subtypes of mild cognitive impairment (MCI) reflect different disease etiologies. In this study, we examined the extent to which cognitive profiles of nondemented patients with MCI diagnosed with prodromal Alzheimer's disease (AD) differed from those MCI patients diagnosed with vascular disease. We also compared these diagnostic groups to mildly demented patients diagnosed with AD and normal elderly controls. Results indicate that a majority of both MCI-AD and MCI-vascular patients experienced amnestic features and that multiple-domain was the most common presentation. MCI-AD and MCI-vascular groups did not differ on neuropsychological measures tapping memory, language, visuospatial skills/praxis or executive function. Further both MCI groups could be distinguished from dementia patients with regards to performance on measures of memory but not on non-memory measures. Considerable variability was observed in the degree of memory impairment among MCI patients with scores as much as 6 standard deviations below expected mean values. MCI-AD and MCI-vascular patients frequently exhibit both common and overlapping amnestic and nonamnestic features. The implication of these findings for future clinical research is discussed. [ABSTRACT FROM AUTHOR]

Objective: This study examined the association between the Apolipoprotein-E epsilon4 allele (APOE epsilon4) and age of disease onset in a bi-ethnic sample of community dwelling Alzheimer's disease (AD) patients.Design: Cross-sectional study of AD patients evaluated at a University-affiliated outpatient memory disorders clinic.Subjects: A clinic-based cohort of white non-Hispanic (WNH; n=601) and white Hispanic (WH; n = 359) patients diagnosed with possible or probable AD according to NINCDS-ADRDA diagnostic criteria.Measures: Global cognitive functioning of the subjects was evaluated using the Mini-mental State Exam. The age of onset of AD was calculated from the patient's current age minus the reported duration of disease obtained from a knowledgeable family member.Results: A significant relationship was discovered between APOE epsilon4 and age of onset for WNH, with lower ages of onset among patients carrying the epsilon4/epsilon4 and epsilon3/epsilon4 genotypes in relation to patients with the epsilon3/epsilon3 genotype. The results revealed a more modest effect for APOE genotype in the WH cohort, with a lower age of onset witnessed among epsilon4 positive patients (epsilon2/epsilon4, epsilon3/epsilon4 and epsilon4/epsilon4 genotypes) in comparison to epsilon4 negative patients (epsilon2/epsilon2, epsilon2/epsilon3 and epsilon3/epsilon3 genotypes).Conclusion: The association between the epsilon4 allele and earlier age of onset was more pronounced in WNH compared to WH patients, suggesting the impact of APOE polymorphism on clinical phenotype may be different for distinct ethnic groups in the U.S. [ABSTRACT FROM AUTHOR]

Poorer self-rated physical health represents an important outcome of dementia caregiving. However, the impact of specific caregiver and patient factors on this variable remains unclear. This study investigated factors associated with perceived health status among 64 white non-Hispanic family caregivers of community-dwelling Alzheimer's disease (AD) patients. In the current study, greater depressive symptoms reported by the caregiver and older caregiver age predicted poorer self-rated health. The results suggest caregiver variables, rather than patient characteristics, are the principal factors impacting the perceived physical adjustment of AD family caregivers in the community. [ABSTRACT FROM AUTHOR]

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.

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 (Aβ-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 Aβ-PET., Results: A total of 239 participants underwent blood draw and Aβ-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 Aβ-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 Aβ-PET (95.8%) than high p-tau217 and positive Aβ-PET (86.3%). Analyses within ethnicity-specific subgroups suggested similar p-tau217 performance., Discussion: Plasma p-tau217 (ALZPath) relates to brain Aβ 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 Aβ-PET were measured in Hispanic/Latino and non-Hispanic/Latino older adults.Plasma p-tau217 accurately discriminated Aβ-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 Aβ-PET were strong within both Hispanic/Latino and non-Hispanic/Latino groups., Competing Interests: The authors report no disclosures relevant to the content of this work. STDeK reports being a consultant with Biogen, Prevail, Vaccinex, and Acumen Dementia. DEV reports consulting for Neuroimaging Solutions. All other authors report no disclosures. Author disclosures are available in the Supporting information., (© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: We aimed to evaluate the psychometric properties and diagnostic accuracy of the 32-item version of the Multilingual Naming Test (MINT) in participants from 2 ethnic groups (European Americans [EA; n = 106] and Hispanic Americans [HA; n = 175]) with 3 diagnostic groups (cognitively normal [CN], n = 94, mild cognitive impairment [MCI], n = 148, and dementia, n = 39)., Method: An Item Response Theory model was used to evaluate items across ethnicity and language groups (Spanish and English), resulting in a 24-item version. We analyzed the MINT discriminant and predictive validity across diagnostic groups., Results: A total of 8 items were differentially difficult between languages in the 32-item version of the MINT. EA scored significantly higher than HA, but the difference was not significant when removing those 8 items (controlling for Education). The Receiver Operating Characteristics showed that the MINT had poor accuracy when identifying CN participants and was acceptable in identifying dementia participants but unacceptable in classifying MCI participants. Finally, we tested the association between MINT scores and magnetic resonance imaging volumetric measures of language-related areas in the temporal and frontal lobes. The 32-item MINT in English and Spanish and the 24-item MINT in Spanish were significantly correlated with the bilateral middle temporal gyrus. The left fusiform gyrus correlated with MINT scores regardless of language and MINT version. We also found differential correlations depending on the language of administration., Conclusions: Our results highlight the importance of analyzing cross-cultural samples when implementing clinical neuropsychological tests such as the MINT., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: The LASSI-L measure was developed by RC and DL at the University of Miami, who hold intellectual property rights. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Curiel Cid, Crocco, Duara, Vaillancourt, Asken, Armstrong, Adjouadi, Georgiou, Marsiske, Wang, Rosselli, Barker, Ortega, Hincapie, Gallardo, Alkharboush, DeKosky, Smith and Loewenstein.)

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 Aβ-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 Aβ-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 Aβ-PET[+] and Aβ-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., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

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-β peptide fragments (Aβ42/Aβ40), 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., Competing Interests: The LASSI-L measure was developed by DL and RC at the University of Miami, who holds intellectual property rights. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Curiel Cid, Ortega, Crocco, Hincapie, McFarland, Duara, Vaillancourt, DeKosky, Smith, Sfakianaki, Rosselli, Barker, Adjouadi, Barreto, Feito and Loewenstein.)

Objective: The interaction of ethnicity, progression of cognitive impairment, and neuroimaging biomarkers of Alzheimer's Disease remains unclear. We investigated the stability in cognitive status classification (cognitively normal [CN] and mild cognitive impairment [MCI]) of 209 participants (124 Hispanics/Latinos and 85 European Americans)., Methods: Biomarkers (structural MRI and amyloid PET scans) were compared between Hispanic/Latino and European American individuals who presented a change in cognitive diagnosis during the second or third follow-up and those who remained stable over time., Results: There were no significant differences in biomarkers between ethnic groups in any of the diagnostic categories. The frequency of CN and MCI participants who were progressors (progressed to a more severe cognitive diagnosis at follow-up) and non-progressors (either stable through follow-ups or unstable [progressed but later reverted to a diagnosis of CN]) did not significantly differ across ethnic groups. Progressors had greater atrophy in the hippocampus (HP) and entorhinal cortex (ERC) at baseline compared to unstable non-progressors (reverters) for both ethnic groups, and more significant ERC atrophy was observed among progressors of the Hispanic/Latino group. For European Americans diagnosed with MCI, there were 60% more progressors than reverters (reverted from MCI to CN), while among Hispanics/Latinos with MCI, there were 7% more reverters than progressors. Binomial logistic regressions predicting progression, including brain biomarkers, MMSE, and ethnicity, demonstrated that only MMSE was a predictor for CN participants at baseline. However, for MCI participants at baseline, HP atrophy, ERC atrophy, and MMSE predicted progression.

Objective: To provide high-quality healthcare, it is essential to understand values that guide the healthcare decisions of older adults. We investigated the types of values that culturally diverse older adults incorporate in medical decision making., Methods: Focus groups were held with older adults who varied in cognitive status (mildly impaired versus those with normal cognition) and ethnicity (Hispanic and non-Hispanic). Investigators used a qualitative descriptive approach to analyze transcripts and identify themes., Results: Forty-nine individuals (49% with cognitive impairment; 51% Hispanic) participated. Participants expressed a wide range of values relating to individual factors, familial/cultural beliefs and expectations, balancing risks and benefits, receiving decisional support, and considering values other than their own. Participants emphasized that values are individual-specific, influenced by aging, and change throughout life course. Participants described barriers and facilitators that interfere with or promote value solicitation and incorporation during medical encounters., Conclusion: Study findings highlight that in older adults with various health experiences, cognitive and physical health status, and sociocultural backgrounds, medical decisions are influenced by a variety of values., Practical Implications: Clinicians should take time to elicit, understand, and reassess the different types of values of older adults., (Copyright © 2021 Elsevier B.V. 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.

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To analyze (1) whether there are ethnic differences in the severity of depressive symptoms between groups of elders classified as cognitively normal (CN) or amnestic mild cognitive impairment (aMCI) and (2) the influence of depressive symptoms on specific cognitive performance by ethnicity across diagnoses, controlling for covariates., Methods: 164 Hispanics residing in the United States (HAs) and European Americans (EAs) (100 women; Mage = 72.1, SD = 8.0) were diagnosed as either CN or aMCI. Depressive symptoms were measured with the Geriatric Depression Scale (GDS-15). Cognition was assessed using the Loewenstein-Acevedo Scales for Semantic Interference and Learning (semantic memory), Multilingual Naming Test (confrontation naming), and the Stroop Test (Color-Word condition; executive function). A 2 × 2 univariate ANCOVA as well as linear and logistic regressions explored differences in depressive symptoms among diagnostic and ethnic groups., Results: Higher depression was seen in aMCI compared to the CN group for both ethnicities, after controlling for age, education, gender, and Mini-Mental State Examination score. Greater levels of depression also predicted lower scores in confrontation naming and semantic memory for only the EA group and marginally in scores of executive function for HA participants. GDS-15 scores of ≤ 4 also predicted less likelihood of aMCI diagnosis., Conclusions: Severity of depressive symptoms was associated with greater cognitive impairment, independent of ethnicity. Significant results suggest detrimental effects of depression on clinical diagnoses most evidently for subjects from the EA group., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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).

The threshold for amyloid positivity by visual assessment on PET has been validated by comparison to amyloid load measured histopathologically and biochemically at post mortem. As such, it is now feasible to use qualitative visual assessment of amyloid positivity as an in-vivo gold standard to determine those factors which can modify the quantitative threshold for amyloid positivity. We calculated quantitative amyloid load, measured as Standardized Uptake Value Ratios (SUVRs) using [18-F]florbetaben PET scans, for 159 Hispanic and non-Hispanic participants, who had been classified clinically as Cognitively Normal (CN), Mild Cognitive Impairment (MCI) or Dementia (DEM). PET scans were visually rated as amyloid positive (A+) or negative (A-), and these judgments were used as the gold standard with which to determine (using ROC analyses) the SUVR threshold for amyloid positivity considering factors such as age, ethnicity (Hispanic versus non-Hispanic), gender, cognitive status, and apolipoprotein E ε4 carrier status. Visually rated scans were A+ for 11% of CN, 39.0% of MCI and 70% of DEM participants. The optimal SUVR threshold for A+ among all participants was 1.42 (sensitivity = 94%; specificity = 92.5%), but this quantitative threshold was higher among E4 carriers (SUVR = 1.52) than non-carriers (SUVR = 1.31). While mean SUVRs did not differ between Hispanic and non-Hispanic participants;, a statistically significant interaction term indicated that the effect of E4 carrier status on amyloid load was greater among non-Hispanics than Hispanics. Visual assessment, as the gold standard for A+, facilitates determination of the effects of various factors on quantitative thresholds for amyloid positivity. A continuous relationship was found between amyloid load and global cognitive scores, suggesting that any calculated threshold for the whole group, or a subgroup, is artefactual and that the lowest calculated threshold may be optimal for the purposes of early diagnosis and intervention., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

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).

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., (© 2018 American Academy of Neurology.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

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., (Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: This study examined the association between a history of heavy alcohol use and smoking, presence of the apolipoprotein-E epsilon 4 allele (APOE epsilon4), and age of disease onset in a community dwelling sample of 685 Alzheimer's disease (AD) patients spanning three ethnic groups., Design: Cross-sectional study of AD patients evaluated at a University-affiliated outpatient memory disorders clinic., Subjects: A clinic-based cohort of white non-Hispanic (WNH; n = 397), white Hispanic (WH; n = 264), and African-American (AA; n = 24) patients diagnosed with possible or probable AD according to NINCDS-ADRDA diagnostic criteria., Measurements: The age of onset of AD was obtained from a knowledgeable family member. All patients were assessed for APOE genotype. History of alcohol and tobacco consumption prior to the onset of dementia was obtained via an interview with the patient and the primary caregiver. A history of heavy drinking was defined as >2 drinks per day and a history of heavy smoking was defined as > or =1 pack per day., Results: Presence of an APOE epsilon4 allele, a history of heavy drinking, or a history of heavy smoking were each associated with an earlier onset of AD by 2-3 years. Patients with all three risk factors were likely to be diagnosed with AD nearly 10 years earlier than those with none of the risk factors., Conclusion: The results suggest that APOE epsilon4 and heavy drinking and heavy smoking lower the age of onset for AD in an additive fashion.

Background and Purpose: White matter hyperintensities (WMHs) are frequently characterized as markers of cerebrovascular disease, whereas medial temporal atrophy (MTA) is a recognized marker of Alzheimer disease (AD). Our purpose was to test the reliability of a visual rating system (VRS) in evaluating WMHs and MTA and in distinguishing healthy from cognitively impaired subjects., Materials and Methods: Subjects (n = 192) enrolled in the Florida Alzheimer's Disease Research Center were diagnosed with no cognitive impairment, nonamnestic mild cognitive impairment (na-MCI), amnestic MCI (a-MCI), or probable AD. The severity of WMHs was assessed on T2-weighted fluid-attenuated inversion recovery axial MR images, and the severity of MTA was evaluated on 1.5-mm-thick coronal MR images by using a computer-based visual rating system. Cardiovascular risk factor scores were calculated as the sum of 10 independent cardiovascular risk factors., Results: WMH and MTA scores were greater in subjects with probable AD, relative to those with no cognitive impairment and na-MCI. MTA scores differentiated subjects with a-MCI from those with no cognitive impairment and na-MCI. The total WMH score was significantly related to MTA (r = 0.39; P < .001) but not to cardiovascular risk factor scores (r = 0.07; P = not significant). The overall correct classification rate of probable AD versus no cognitive impairment by using MTA scores was 81.8%, improving to 86.5% when combined with WMH scores., Conclusions: Both MTA and WMH scores distinguished subjects with no cognitive impairment and probable AD. Combining MTA and WMH scores improved the correct classification rate, whereas WMH scores were significantly related to MTA scores, but not to cardiovascular risk factor scores. This finding suggests that among subjects with a-MCI and probable AD, WMHs on MR images are primarily associated with neurodegenerative disease.

The purpose of this study was to evaluate whether distinct subtypes of depression could be identified in patients with Alzheimer's disease and, if so, to evaluate the patients in these subgroups. Ratings on the Cornell Scale for Depression in Dementia (CSDD) of 306 patients with Alzheimer's disease, 129 of whom were Spanish- and 177 English-speaking, were subjected to latent class analysis. Four subgroups were identified based on CSDD symptoms. These included an asymptomatic group, groups with mild and more severe typical depression, and a group characterized by prominent anxiety and irritability in addition to sadness. Group differences on demographic, cognitive, clinical, and functional status measures were explored via chi-square tests and analyses of variance. Results show that for some patients with Alzheimer's disease, patterns of symptoms of depression are similar to those in younger adult populations. A distinct subtype may exist, however, with prominent anxiety and irritability.

Objective: Although mild cognitive impairment (MCI) is characterized by performance on memory and other measures below expected normative values, neither a scientific rationale nor a consensus exists regarding which measures have the most use or the optimal cutoffs to use to establish impairment., Methods: Different memory measures were administered to 80 normal community-dwelling subjects divided into two age groups. This provided conormed data on eight different memory indices by which to compare 23 nondemented clinically diagnosed patients with MCI who met all other criteria for Alzheimer disease (AD)., Results: On immediate memory for passages, delayed visual reproduction, object memory, and a measure sensitive to semantic interference, 70%-78% of patients with MCI were identified as impaired at 1.5 standard deviations or greater below expected levels. Conditional logistical regression for age-matched samples indicated that consideration of raw scores for these neuropsychologic tests in combination did not significantly change the odds of MCI diagnosis. When impairment relative to the total normal elderly sample was calculated based on one or more impairments at a 1.5 or greater cutoff, specificity fell below acceptable levels when more than three memory measures were considered., Conclusion: An array of widely used neuropsychologic measures demonstrated utility in distinguishing patients with MCI-AD from cognitively normal community-dwelling elders. The appropriateness of more or less stringent cutoffs was highly influenced by the number of measures considered. These findings have important implications regarding the choice of cut points for impairment used for the diagnosis of MCI in both research and clinical settings.

The cyclooxygenase-2 enzyme (COX-2) is of particular importance in the inflammatory response and recent findings have demonstrated a considerable role in Alzheimer's disease (AD) pathogenesis. In order to assess the possible putative role of a COX-2 polymorphism (765G/C) in AD, we examined its distribution in 161 community-based controls and 168 AD clinic-based cases previously recruited from memory disorder clinics in Tampa and Miami, Florida. There were no significant differences between the two groups in age/age of onset or gender. A significant difference was observed in the distribution of the COX-2 -765 alleles between AD cases and controls (chi(2) = 6.565, p = .010; OR = .596; CI = [.401-.888], p = .011), with the frequency of the C allele being higher in controls. In addition, a significant difference was observed for this polymorphism by genotype (chi(2) = 6.561, p = .038) and by presence or absence of C+ genotypes (chi(2) = 6.207, p = .013; OR = .464, CI = [.351-.885], p = .013). In this sample, the C allele of COX-2 -765 promoter polymorphism is associated with decreased risk of Alzheimer's disease, a finding which further supports the involvement of COX-2 in AD etiology.

Mild cognitive impairment (MCI), a major risk factor for dementia, has an amnestic subtype that has a high probability of progressing to Alzheimer's disease. The rate of progression may be predicted by the severity of memory impairment at baseline, the severity of hippocampal atrophy, and, possibly, the presence of an epsilon4 allele of the apolipoprotein E gene. MCI can be diagnosed using purely clinical or a combination of clinical and neuropsychologic criteria. Treatment trials show no disease-modifying effect. The radiologists' role is to determine whether or not the hallmarks of degenerative and vascular disease of the brain are present, aiding in the diagnosis of the cause of MCI.

Context: Alzheimer Disease (AD) is often diagnosed at a moderately advanced stage, even though its early detection has become increasingly important, because of the continuing development of treatments that may improve its outcome., Objective: To determine if a free memory screening program is associated with an earlier diagnosis of AD, compared with traditional referral methods, such as by physicians and family members., Design, Setting, and Participants: A retrospective study of 1489 consecutive patients with AD who presented to an outpatient memory disorders clinic between 1993 and 2002. Subjects were classified according to referral source (memory screening, physician, family/friend, other), and self-reported ethnicity (white non-Hispanic, white Hispanic). The associations between referral source and the presenting cognitive and behavioral status of subjects were evaluated using analysis of variance and logistic regression analyses, after controlling for potentially confounding factors., Main Outcome Measures: Score on the Folstein Mini-Mental State Examination (MMSE), duration of cognitive symptoms, and presence of psychosis, defined as delusions and/or hallucinations., Results: After controlling for ethnicity, gender, and the year of diagnosis, subjects with AD, who were referred by the memory screening program, scored significantly higher at presentation on the MMSE (20.8 +/- 5.7), than those referred by physicians (18.8 +/- 6.6), family/friends (16.8 +/- 6.6), or other referral sources (15.3 +/- 7.1). Subjects with AD, referred by the memory screening program, also had a lower reported duration of illness at presentation, and a decreased frequency of psychosis compared with those referred by family/friend and other methods. Other factors related to a diagnosis of AD at a later stage included female gender, Hispanic ethnicity, and a diagnosis early in the 1993 to 2002 time period., Conclusions: The memory screening program referred patients with AD to a memory clinic at an earlier phase of illness compared with traditional methods such as physician referral.

Objective: This cross-sectional study examined the relationship between subjective memory complaints and the apolipoprotein epsilon 4 allele (epsilon4), a genetic risk factor for Alzheimer's disease (AD), among cognitively normal subjects identified from a community memory screening., Design: The sample comprised 232 consecutive white non-Hispanic older adults who presented to a free community-based memory-screening program at a University affiliated memory disorders center. Participants were classified as cognitively normal based on scores on the age and educated adjusted Folstein Mini-Mental Status Exam (MMSAdj) and a brief Delayed Verbal Recall Test (DRT). Subjects were assessed for APOE genotype, subjective memory complaints (Memory Questionnaire, MQ), depressive symptoms (Hamilton Depression Rating Scale, HDRS), and history of four major medical conditions that have been associated with memory loss (stroke/transient ischemic attack [TIA], atherosclerotic heart disease, hypertension, and diabetes). A hierarchical regression analysis was performed to examine the association between APOE genotype and memory complaints after controlling for a host of potential confounding factors., Results: The APOE epsilon4 allele frequency for cognitively normal subjects was 0.13. Subjective memory complaints were predicted by depressive symptoms and a history of stroke/TIA. They were not associated with APOE genotype, MMSAdj score, DRT score, age, education, gender, and reported history of atherosclerotic heart disease, hypertension, or diabetes., Conclusion: The results did not suggest an association between subjective memory complaints and the APOE epsilon4 allele in this sample of cognitively intact subjects. This indicates that memory complaints may confer risk for future dementia through pathways independent of APOE genotype. The results also show that older adults with memory complaints are at increased risk for underlying depression., (Copyright (c) 2004 John Wiley & Sons, Ltd.)

Impairment in delayed recall has traditionally been considered a hallmark feature of Alzheimer's disease (AD). However, vulnerability to semantic interference may reflect early manifestations of the disorder. In this study, 26 mildly demented AD patients (mild AD), 53 patients with mild cognitive impairment without dementia (MCI), and 53 normal community-dwelling elders were first presented 10 common objects that were recalled over 3 learning trials. Subjects were then presented 10 new semantically related objects followed by recall for the original targets. After controlling for the degree of overall memory impairment, mild AD patients demonstrated greater proactive but equivalent retroactive interference relative to MCI patients. Normal elderly subjects exhibited the least amount of proactive and retroactive interference effects. Recall for targets susceptible to proactive interference correctly classified 81.3% of MCI patients and 81.3% of normal elderly subjects, outperforming measures of delayed recall and rate of forgetting. Adding recognition memory scores to the model enhanced both sensitivity (84.6%) and specificity (88.5%). A combination of proactive and retroactive interference measures yielded sensitivity of 84.6% and specificity of 96.2% in differentiating mild AD patients from normal older adults. Susceptibility to proactive semantic interference may be an early cognitive feature of MCI and AD patients presenting for clinical evaluation.

Objective: To determine the conversion rates to dementia in patients diagnosed with mild cognitive impairment (MCI) thought to be caused by incipient Alzheimer's disease (MCI-AD) or with MCI with features of vascular disease (MCI-Vas)., Methods: On the basis of patient history, neurocognitive, neurological and MRI evaluation, 99 patients were diagnosed with MCI-AD and 35 with MCI-Vas. Conversion to dementia over an average of a 2.4 +/- 1.8-year period was determined., Results: Over the follow-up period, 44% converted to dementia, 51.5% remained classified as MCI, and 4.5% were reclassified as cognitively normal. The conversion rate to dementia was significantly faster at 3 years for the MCI-AD (50.5%) than for the MCI-Vas group (25.7%). The neuropsychological test found to best differentiate converters from non-converters was the Fuld-OME, a measure of learning and recall. Age, education, gender or APOE epsilon4 allele frequency did not differentiate converters from non-converters., Conclusions: MCI-AD and MCI-Vas are clinically meaningful subtypes of MCI that may convert to dementia at different rates. Prospective studies on larger subsets of MCI patients are required to confirm these findings., (2004 S. Karger AG, Basel)

Objective: The authors evaluated the usefulness and psychometric properties of the Semantic Interference Test (SIT) in patients with mild Alzheimer disease (AD)., Methods: Subjects were first presented with 10 common objects to be learned over three trials. Proactive interference was assessed by having subjects recall 10 new objects that were semantically related to the previous ones. Retroactive interference was assessed by having subjects recall the original 10 objects., Results: Controlling for overall memory impairment, very mildly impaired AD patients demonstrated significantly greater proactive and retroactive interference effects than the normal, community-dwelling comparison group. The proactive score alone and the combined proactive-plus-retroactive score index were more effective than traditional neuropsychological measures of delayed recall in distinguishing between the very mildly impaired AD group and the normal-comparison group., Conclusion: The authors discuss the potential usefulness of the SIT in identifying vulnerability to semantic interference in early AD.

Alzheimer disease (AD) is the most common dementing illness in the elderly, but there is equivocal evidence regarding the frequency of other disorders such as Lewy body disease (LBD), vascular dementia (VaD), frontotemporal dementia (FTD), and hippocampal sclerosis (HS). This ambiguity may be related to factors such as the age and gender of subjects with dementia. Therefore, the objective of this study was to calculate the relative frequencies of AD, LBD, VaD, FTD, and HS among 382 subjects with dementia from the State of Florida Brain Bank and to study the effect of age and gender on these frequencies. AD was the most frequent pathologic finding (77%), followed by LBD (26%), VaD (18%), HS (13%), and FTD (5%). Mixed pathology was common: Concomitant AD was present in 66% of LBD patients, 77% of VaD patients, and 66% of HS patients. The relative frequency of VaD increased with age, whereas the relative frequencies of FTD and LBD declined with age. Males were overrepresented among those with LBD, whereas females were overrepresented among AD subjects with onset age over 70 years. These estimates of the a priori probabilities of dementing disorders have implications for clinicians and researchers.

Objective: The relationship between the epsilon 4 allele of the apolipoprotein E gene (APOE-epsilon4) located on chromosome 19 and Alzheimer's disease is well documented among Caucasian populations. However, the findings of research addressing the link between APOE polymorphism and neurocognitive functioning in populations of African origin from around the world have been equivocal. Therefore, the current study explored the relation of APOE-epsilon4 with cognitive impairment in a sample of community-dwelling English-speaking elderly blacks., Methods: All participants (N = 57) were recruited consecutively from a community memory-screening program at a University affiliated Memory Disorders Clinic and evaluated using standardized assessment procedures. Cognitive impairment was classified according to an age and education adjusted Mini-Mental State Exam score of less than 24 as well as poorer functioning on a measure of delayed verbal memory., Results: Increased risk for global cognitive dysfunction (OR = 9.5, 95 percent CI = 2.3-55.3, p = .004) and poorer verbal recall performance (beta = -.36, p = .006) were linked with the APOE epsilon4 allele after controlling for the potentially confounding effects of age, education, and gender., Conclusions: This investigation supports the role of APOE polymorphism in determining neurocognitive impairment among black elders residing in the community.

The epsilon 4 (epsilon 4) and epsilon 2 (epsilon 2) alleles of the apolipoprotein gene (APOE) located on chromosome 19 have been associated with increased and decreased risk for Alzheimer disease (AD) in older adults, respectively. However, there is a dearth of studies examining the relation of APOE polymorphism with cognitive functioning among community-dwelling ethnic minority elderly. This study examined the risk for cognitive impairment associated with the APOE epsilon 4 and epsilon 2 alleles in a community-based cohort of non-Hispanic white (NHW; N = 739) and white Hispanics (WH; N=321). All patients were recruited consecutively from a memory-screening program and evaluated using standardized assessment procedures. Cognitive impairment was classified according to an age and education adjusted Folstein Mini-Mental State Exam (MMSAdj) score of less than 24. The results indicated the APOE epsilon 4 allele was associated with increased risk for cognitive dysfunction in NHW and WH after controlling for the effects of age, education, and gender. This risk was generally observed to be dose-dependent, with greater risk among epsilon 4 homozygotes in relation to epsilon 4 heterozygotes. The epsilon 2 allele of APOE did not confer decreased risk for cognitive impairment among NHW and WH. This study supports the relation of APOE polymorphism to cognitive dysfunction among two ethnic populations residing in the community.

The authors examined the prevalence and clinical correlates of mood disturbance in 96 Cuban American (CA) Alzheimer's disease (AD) patients. Depression (Cornell Scale for Depression in Dementia score > or = 7) was evident in 39.6% of the participants and showed associations with comorbid psychosis, lower education, and decreased length of residence in the United States, a measure of acculturation. Mood disturbance was not related to age, gender, marital status, cognitive dysfunction, functional impairment, history of significant alcohol use, or coexisting medical conditions. The results of this investigation suggest that signs and symptoms of depression are common neuropsychiatric disturbances in CA AD patients residing in the community.

Category fluency tasks are an important component of neuropsychological assessment, especially when evaluating for dementia syndromes. The growth in the number of Spanish-speaking elderly in the United States has increased the need for appropriate neuropsychological measures and normative data for this population. This study provides norms for English and Spanish speakers, over the age of 50, on 3 frequently used measures of category fluency: animals, vegetables, and fruits. In addition, it examines the impact of age, education, gender, language, and depressed mood on total fluency scores and on scores on each of these fluency measures. A sample of 702 cognitively intact elderly, 424 English speakers, and 278 Spanish speakers, participated in the study. Normative data are provided stratified by language, age, education, and gender. Results evidence that regardless of the primary language of the examinee, age, education, and gender are the strongest predictors of total category fluency scores, with gender being the best predictor of performance after adjusting for age and education. English and Spanish speakers obtained similar scores on animal and fruit fluency, but English speakers generated more vegetable exemplars than Spanish speakers. Results also indicate that different fluency measures are affected by various factors to different degrees.

There is a relative dearth of studies examining the cognitive and neuropsychiatric features of black Alzheimer's disease (AD) patients in the United States. Therefore, this cross-sectional investigation reported on the prevalence and clinical correlates of depression and psychosis in a community-dwelling black AD sample. The study participants comprised 55 English-speaking black patients evaluated consecutively at a university-affiliated memory disorders clinic. All patients were evaluated utilizing standardized procedures and diagnosed with possible or probable AD according to the criteria established by the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Disorders Association. The presence of neuropsychiatric symptoms, including major depression and psychosis (delusions or hallucinations) was established via a semistructured psychiatric interview with the patient and primary care giver. The level of global cognitive impairment was rated with the Mini-Mental State Examination. The results showed that major depression and psychosis were observed in 20% and 58% of the sample, respectively. Mood disturbance was linked with low education, whereas psychosis was associated with greater cognitive dysfunction. This study provides important insight into the clinical characteristics of community-dwelling black AD patients. It is clear that continued research in the area of ethnicity and dementia is warranted to better understand the clinical needs of blacks and other minority populations in the United States that are afflicted with AD.

Since it has been postulated that mood disturbance in nondemented older adults may represent a prodromal feature of dementia for a subgroup of patients, it would be expected that patients with these symptoms would evidence a greater prevalence of family history of dementia. In a sample of 3225 community-dwelling cognitively intact elderly recruited from a free memory-screening program, we found that current depression was more common in participants with a positive versus a negative family history of dementia in first-degree relatives (17% versus 11%; Fisher's Exact Test, P < .0001). This relationship remained significant after controlling for age, education, gender, ethnicity, and Folstein Mini-Mental State Examination score (OR = 1.5; 95% CI = 1.2-1.9, Wald X2 = 15.5, P < .001). The results suggest that symptoms of depression may herald the onset of an incipient dementia syndrome in a subset of geriatric patients. Alternatively, the results may be indicative of familial aggregation of dementia and depression.

Objective: This study investigated predictors of positive (satisfaction) and negative (burden) appraisal among Cuban American (CA) caregivers of Alzheimer's disease (AD) patients., Design: Cross-sectional study of AD patients and their family caregivers., Setting: A university-affiliated outpatient memory disorders clinic., Subjects: A convenience sample of 40 CA family caregivers of patients diagnosed with probable or possible AD according to NINCDS-ADRDA diagnostic criteria., Measures: AD patients: Mini-Mental State Examination (MMSE), Blessed Dementia Scale (BDS) and the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). Caregivers: Caregiving Burden Scale (CBS), Caregiving Satisfaction Scale (CSS), Perceived Emotional Support scale (PES) and the Short Form-36 Health Survey-General Health Index (GH)., Results: Appraised burden was predicted by increased patient behavioral pathology, female caregiver gender and lower levels of perceived emotional support. The association between older caregiver age and increased burden approached significance. Older caregiver age and higher levels of perceived social support were shown to predict appraised satisfaction. Post-hoc analyses also indicated that length of residence in the United States, a measure of acculturation, was not associated with positive or negative appraisal., Conclusion: Appraised burden and satisfaction represent important outcomes of dementia care that show relations with distinct factors among CA caregivers. It is clear that further research is warranted in order to ascertain the relationship of ethnicity or culture to the process and psychological consequences of dementia caregiving. Continued investigations into predictors of caregiving satisfaction are also recommended., (Copyright 2000 John Wiley & Sons, Ltd.)

The objective of this study was to test the utility of additional delayed recall of the three recall items of the Folstein Mini Mental State Evaluation (MMSE) as a screening measure for mild cognitive impairment and dementia in the elderly. It used a cross-sectional study of subjects, who were administered a brief memory screening battery which included the MMSE and extended delayed recall of the three MMSE recall items at 5 minute intervals. The criteria for cognitive status was determined on the basis of the neurological and neuropsychological evaluation. One hundred and two elderly persons who were recruited through a memory screening program were diagnosed as cognitively normal (N=52), mild cognitively impaired (N=24), or demented (N=26). The observed sensitivity of 83.3% and specificity of 90.4% was achieved across three delayed recall trials in differentiating cases with mild cognitive impairment (without dementia) from individuals with normal cognition and was superior to the total MMSE score alone (sensitivity/specificity: 70.8%/84.6%). Cumulative recall for the three MMSE items across only two delayed recall trials demonstrated a sensitivity of 96.2% and specificity of 90.4% in differentiating between cases of dementia versus cases diagnosed with no cognitive impairment. The three trial delayed recall score enhanced prediction of mild cognitive impairment in at-risk elderly living with the community and may have promise in the development of future screening batteries., (Copyright 2000 John Wiley & Sons, Ltd.)

Objective: This cross-sectional study examined the relationship of behavioral and psychological symptoms to cognitive and functional impairment in Alzheimer's disease (AD)., Design: One hundred and fourteen patients were evaluated consecutively at a university-affiliated outpatient memory disorders clinic and diagnosed with possible or probable Alzheimer's disease (AD) according to NINCDS-ADRDA criteria. Subjects were assessed with the Behavioral Pathology in Alzheimer's Disease Scale (BEHAVE-AD), Revised Memory and Behavior Problem Checklist (RMBPC), Blessed Dementia Scale (BDS), and Mini-Mental State Examination (MMSE)., Results: Several symptoms of behavioral pathology showed associations with MMSE scores, including activity disturbances, delusions, and hallucinations. After controlling for the variance associated with the MMSE, activity disturbances, diurnal disturbances, delusions, and hallucinations were linked with BDS scores., Conclusions: The results suggest that some non-cognitive symptoms may be related to the neurobiologic mechanisms underlying the increased cognitive dysfunction in AD. Specific symptoms of behavioral pathology may also impact a patient's ability to perform important self-maintenance behaviors., (Copyright 2000 John Wiley & Sons, Ltd.)

Objective: To evaluate the sensitivity and specificity of the clinical features of three published diagnostic criteria for diffuse Lewy body disease (DLBD) using autopsy-confirmed Alzheimer's (AD), DLBD and AD+DLBD (mixed) dementia cases., Design: Retrospective chart review of an autopsy series of 56 patients selected from the State of Florida Brain Bank on the basis of a pathological diagnosis of either pure AD, DLBD (pure and common forms) or AD+DLBD (mixed) dementia. Clinical features were assessed by three raters blind to the pathological diagnosis., Results: The existing criteria for a clinical diagnosis of DLBD were highly specific (90-100%) but not very sensitive (49-63%) in the differential diagnosis of DLBD versus AD; sensitivity did improve (61-74%) when mixed AD+DLBD cases were eliminated. Clinical features that occur more frequently in DLBD than in AD were unspecified hallucinations, unspecified EPS, fluctuating course and rapid progression. Post-hoc analysis also indicated that hallucinations and EPS were more common early in the disease course of DLBD than in AD. Empirically derived criteria, formulated using the most prevalent clinical features, demonstrated sensitivity values of 57-96% for pure forms and 43-91% for mixed forms., Conclusions: This study demonstrated that additional improvements in the established criteria for DLBD are needed. Our empirically derived criteria enhanced the distinction of DLBD from AD while allowing the clinician the choice of maximizing sensitivity with acceptable specificity, and vice versa., (Copyright 1999 John Wiley & Sons, Ltd.)

The relationship between a premorbid history of depression and the depressive syndrome in Alzheimer's disease (AD) remains equivocal. In the current study, we compared the prevalence of depression among patients with and without a history of mood disturbance prior to the onset of dementia. The sample comprised 243 AD outpatients evaluated consecutively at a university-affiliated memory disorders center. The results indicated that a positive history of depression was more common among patients with current depression compared to those without current depression (23% vs 11%, Fisher's Exact Test, P = .03). This relationship remained significant after controlling for the effects of age, education, gender, ethnicity, and level of cognitive impairment (odds ratio = 2.6, 95% confidence interval = 1.01-6.61, P = .04). Neither gender nor the interaction of gender and history of depression was shown to confer risk for current depressive symptoms. The present investigation suggests that premorbid depression may alter the risk for mood disturbance in AD.