José R. Carrión-Baralt

Professional Considerations for Improving the Neuropsychological Evaluation of Hispanics: A National Academy of Neuropsychology Education Paper

In a national survey, 82% of U.S. neuropsychologists who offered services to Hispanics self-reported inadequate preparation to work with this population (Echemendia, Harris, Congett, Diaz, & Puente, 1997). The purpose of this paper is to improve the quality and accessibility of neuropsychological services for Hispanic people living in the United States by giving guidance for service delivery, training, and organizational policy. General guidance towards this end comes from professional ethics for psychologists and interpreters/translators, federal civil rights law, the International Test Commission, and the Office of Minority Health of the U.S. Department of Health and Human Services, among others. This guidance is specifically applied here to cover professional cultural and linguistic competence of neuropsychologists, psychometrists, interpreters, translators, and consultants; languages of evaluation; use of interpreters; evaluation of acculturation; test translation, adaptation, and interpretation; application of test norms; intervention issues; reimbursement; and organizational issues.

C-reactive protein and memory function suggest antagonistic pleiotropy in very old nondemented subjects

SIR—A possible role of inflammation in the development of dementia [1] has led to investigations examining whether C-reactive protein (CRP), a systemic marker of inflammation, is associated with worse cognitive function and decline in old age. Elevated CRP has been associated with worse global and specific cognitive functioning [2–7], although other studies have found no relationship between CRP and cognition [8–10]. Most studies have examined samples averaging <75 years [3–6, 9, 10]. We hypothesised that elevated CRP would be related to worse cognitive function in very old cognitively healthy subjects.

Impact of APOE ε4 on the Cognitive Performance of a Sample of Non-Demented Puerto Rican Nonagenarians

APOE epsilon4 is a major risk factor for Alzheimers disease. It has also been associated with cognitive impairment and cognitive decline in young-olds, but the impact of the epsilon4 allele on cognitive function in very late life is still unclear. The object of this study was to evaluate the association of the epsilon4 allele of APOE with the cognitive performance of a sample of non-demented oldest-olds. Eighty-seven Spanish-speaking Puerto Rican non-demented nonagenarians were administered a complete neuropsychological assessment and provided a blood sample used for APOE genotyping. A factor analysis generated two factors: 1) verbal memory; and 2) visuo-spatial, naming and attention tasks, accounting for 43.6% of the overall variance in the 13 original neuropsychological variables. The multivariate analysis reflected, after controlling for gender, education, and age, the APOE epsilon4 carriers performed better in overall cognition (both factors analyzed together) than non-carriers (T;{2} = 0.082, F(2,80) = 3.289, p = 0.042). Neither gender nor the gender by APOE epsilon4 status interaction was associated with differences in cognition. In conclusion, the results of this study suggest that, among these Puerto Rican non-demented nonagenarians, being an APOE epsilon4 allele carrier is associated with better cognition.

C-reactive protein and familial risk for dementia: a phenotype for successful cognitive aging.

Objectives: Identifying phenotypes for successful cognitive aging, intact cognition into late-old age (>age 75), can help identify genes and neurobiological systems that may lead to interventions against and prevention of late-life cognitive impairment. The association of C-reactive protein (CRP) with cognitive impairment and dementia, observed primarily in young-elderly samples, appears diminished or reversed in late-old age (75+ years). A family history study determined if high CRP levels in late-old aged cognitively intact probands are associated with a reduced risk of dementia in their first-degree family members, suggesting a familial successful cognitive aging phenotype. Methods: The primary sample was 1,329 parents and siblings of 277 cognitively intact male veteran probands at least 75 years old. The replication sample was 202 relatives of 51 cognitively intact community-ascertained probands at least 85 years old. Relatives were assessed for dementia by proband informant interview. Their hazard ratio (HR) for dementia as a function of the probands log-transformed CRP was calculated using the proportional hazards model. Results: Covarying for key demographics, higher CRP in probands was strongly associated with lower risk of dementia in relatives (HR = 0.55 [95% confidence interval (CI) 0.41, 0.74], p < 0.02). The replication sample relationship was in the same direction, stronger in magnitude, and also significant (HR = 0.15 [95% CI 0.06, 0.37], p < 0.0001). Conclusions: Relatives of successful cognitive aging individuals with high levels of CRP are relatively likely to remain free of dementia. High CRP in successful cognitive aging individuals may constitute a phenotype for familial—and thus possibly genetic—successful cognitive aging.

Heritability of Cognitive Functions in Families of Successful Cognitive Aging Probands from the Central Valley of Costa Rica

We sought to identify cognitive phenotypes for family/genetic studies of successful cognitive aging (SCA; maintaining intact cognitive functioning while living to late old age). We administered a battery of neuropsychological tests to nondemented nonagenarians (n = 65; mean age = 93.4 ± 3.0) and their offspring (n = 188; mean age = 66.4 ± 5.0) from the Central Valley of Costa Rica. After covarying for age, gender, and years of education, as necessary, heritability was calculated for cognitive functions at three pre-defined levels of complexity: specific neuropsychological functions (e.g., delayed recall, sequencing), three higher level cognitive domains (memory, executive functions, attention), and an overall neuropsychological summary. The highest heritability was for delayed recall (h² = 0.74, se = 0.14, p < 0.0001) but significant heritabilities involving memory were also observed for immediate recall (h² = 0.50), memory as a cognitive domain (h² = 0.53), and the overall neuropsychological summary (h² = 0.42). Heritabilities for sequencing (h² = 0.42), fluency (h² = 0.39), abstraction (h² = 0.36), and the executive functions cognitive domain (h² = 0.35) were also significant. In contrast, the attention domain and memory recognition were not significantly heritable in these families. Among the heritable specific cognitive functions, a strong pleiotropic effect (i.e., evidence that these may be influenced by the same gene or set of genes) for delayed and immediate recall was identified (bivariate statistic = 0.934, p < 0.0001) and more modest but significant effects were found for four additional bivariate relationships. The results support the heritability of good cognitive function in old age and the utilization of several levels of phenotypes, and they suggest that several measures involving memory may be especially useful for family/genetic studies of SCA.

The Neuropsychological Performance of Nondemented Puerto Rican Nonagenarians

Background/Aims: While the oldest old are the fastest growing segment of the US population, normative neuropsychological data for nondemented oldest old Spanish speakers are nonexistent. This study sought to evaluate the neuropsychological performance of nondemented nonagenarians residing in Puerto Rico and to compare their results with those of a similar English-speaking sample from New York. Methods: We studied 81 subjects who had a complete CERAD neuropsychological assessment in Spanish. We used multiple regression analysis to predict performance on the CERAD battery and ANCOVA to compare the Puerto Rico and New York samples. Results: In 10 out of the 13 neuropsychological tests administered, education was a significant predictor of performance. There were significant differences between the Puerto Rico and New York groups only in the Trail Making Tests. Conclusions: In this Puerto Rican sample, education was the strongest predictor of neuropsychological performance, which is consistent with previous studies. When education level is properly accounted for, the performance of Puerto Rican nonagenarians in the CERAD battery does not differ from the performance of US English-speaking nonagenarians.

A case-control study of the seasonality effects on schizophrenic births on a tropical island

Abstract A substantial body of evidence from dozens of studies in many different countries suggests an excess number of individuals with schizophrenia are born in winter months. The presence of a seasonality effect in regions with year-round warm climate, however, has rarely been examined. The major purpose of this project was to better understand if the seasonality effect on schizophrenic births that has been reported in other, mostly cold regions of the Northern Hemisphere, also can be detected in a warm, tropical climate. We set out to study birth months as risk factors, quantifying the risk for being born with schizophrenia for every month of the winter season in terms of incidence rate ratios (IRRs) in the central region of Puerto Rico. We also analyzed climatic data in order to determine if there was any correlation between the rate of schizophrenic births ( n =710) to births in the general population ( n =101,248) and average rainfall and temperature for every month of the year in our period of study (January 1932–December 1967). Our results suggest that the risk of developing schizophrenia is 36.5% higher for people born in February than for people born in the other months of the year (95% C.I.=6.6–74.8%). We also found correlations between the rate of schizophrenic to control births for any given month, and rainfall 4 months earlier ( r =0.66, p =0.010), and temperature 5 months earlier ( r =0.64, p =0.013) that remained significant after correcting for multiple comparisons.

Association of Apolipoprotein E-e4 and Dementia Declines with Age

OBJECTIVE To study the association of dementia with apolipoprotein E-e4 (APOE-e4) and its interaction with age in a nonagenarian Costa Rican group (N-sample) and a general elderly contrast group (GE-sample). METHODS In both case-control studies, participants were cognitively intact or diagnosed with dementia. The N-sample (N = 112) was at least age 90 years; the GE-sample (N = 98) was at least age 65 years. RESULTS Dementia and APOE-e4 were not significantly associated in the N-sample, but were in the GE-sample. There was a significant interaction of age with APOE-e4 in the N-sample, but not in the GE-sample. Descriptively dividing the N-sample at the median (age 93 years) showed a group interaction: APOE-e4 was more associated with dementia in the younger N-sample than in the older N-sample, where six of seven APOE-e4 carriers were cognitively intact. CONCLUSIONS The results support the reduction in association of APOE-e4 with dementia in extreme old age, consistent with a survivor effect model for successful cognitive aging.

Non-synonymous variants in the AMACR gene are associated with schizophrenia

BACKGROUND The AMACR gene is located in the schizophrenia susceptibility locus on chromosome 5p13, previously identified in a large Puerto Rican pedigree of Spanish origin. The AMACR-encoded protein is an enzyme involved in the metabolism of branched-chain fatty and bile acids. The enzyme deficiency causes structural and functional brain changes, and disturbances in fatty acid and oxidative phosphorylation pathways observed in individuals with schizophrenia. Therefore, AMACR is both a positional and functional candidate gene for susceptibility to schizophrenia. METHODS The study had a two-step design: we performed mutation analysis of the coding and flanking regions of AMACR in affected members of the pedigree, and tested the detected sequence variants for association with schizophrenia in a Puerto Rican case-control sample (n=383) of Spanish descent. RESULTS AND CONCLUSION We identified three missense variants segregating with the disorder in the family, rs2278008, rs2287939 and rs10941112. Two of them, rs2278008 and rs2287939, demonstrated significant differences in genotype (P = 4 × 10-4, P = 4 × 10-4) and allele (P = 1 × 10-4, P = 9.5 × 10-5) frequencies in unrelated male patients compare to controls, with the odds ratios (OR) 2.24 (95% CI: 1.48-3.40) and 2.25 (95% CI: 1.49-3.38), respectively. The G-C-G haplotype of rs2278008-rs2287939-rs10941112 revealed the most significant association with schizophrenia (P = 4.25 × 10-6, OR = 2.96; 95% CI: 1.85-4.76) in male subjects. There were no statistically significant differences in genotype, allele, and haplotype frequencies between female schizophrenia subjects and controls. Our results suggest that AMACR may play a significant role in susceptibility to schizophrenia in male patients.

Prevalence of Dementia in Puerto Rican Veterans is Higher than in Mainland U.S. Veterans

of the DYNOPTA data set and its application to the question of older driver safety. More such work is needed in this important area, and their current and future contributions will be significant. I object, however, to their expansive use of the MMSE to classify persons with respect to cognitive status without reference to other relevant factors, especially education. I encourage them to rethink their classification system in future studies.