Search

For some cardiovascular risk factors, association with risk for cognitive impairment observed in early old age is reduced, or paradoxically even reversed, as age of outcome increases. Successful cognitive aging is intact cognition in the oldest-old; we define resistant successful cognitive aging as successful cognitive aging despite high risk. The protected survivor model posits that a minority of the general population has a protective factor that mitigates the negative effect of a risk factor on successful cognitive aging for the unprotected majority. As age increases, differential failure rates increase the proportion of survivors with protection. Among the unprotected, the proportion with low risk increases, but among those with protection, high risk and low risk do not differ. Due to differential mortality, half the survivors are eventually protected - a majority among those with high risk, and a minority among those with low risk. According to the protective survivor model, an example of Simpson's paradox, the association of the risk factor with survival does not change within an individual, but the association in the surviving population changes as its age increases. We created quantitative illustrations of a simplified protected survivor model applied to successful cognitive aging to explain how the usual association of a risk factor with cognitive decline is reversed in the very old. In the illustrations, probability of subsequent survival was higher for survivors with high risk (mostly protected) than low risk (mostly not protected), an example of Simpson's paradox. Resistance to disease despite the presence of risk factors is consistent with the presence of countervailing protection. Based on the protected survivor model, we hypothesize that studies seeking protective factors against cognitive decline will be more effective by limiting a successful cognitive aging sample to resistant successful cognitive aging - to contrast with a sample without successful cognitive aging. [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted to investigate whether the duration of type two diabetes with cognitive functioning is regulated by high hemoglobin A1c (HbAlc) levels. Researchers evaluated 897 elderly diabetic patients. They found that there was no link between HbA1c and lower levels of cognition and concluded that the association of duration of type two diabetes with cognitive performance is regulated by long term glycemic control.

The article discusses research which was conducted to investigate the association between apolipoprotein Ee4, dementia and age and to investigate the determinants of successful cognitive aging. Researchers evaluated 98 people who were at least 65 years old. They found that the association between the apolipoprotein and dementia declined with age.

Abstract: There are very few data on the relationship between systolic blood pressure (SBP), diastolic blood pressure (DBP), arterial compliance, and left ventricular structure and function, particularly left ventricular hypertrophy (LVH), in the very elderly (>75 years). SBP and arterial stiffness increase with age, and the question is: which of the two is the main stimulus to LVH? This is a cross-sectional study to compare blood pressure and arterial stiffness measures with regard to their correlations with echocardiographic parameters of LV structure and function, controlling for age and cardiovascular risk factors, in a very elderly population. Arterial stiffness was determined by radial pulse waveform using pulse contour analysis. LV dimensions were measured by transthoracic M-mode echocardiography, and diastolic function by tissue Doppler measurements of diastolic mitral annular velocities. There were 179 subjects, all male, with a mean age of 81.8 years. Using age-adjusted partial correlations, SBP, DBP, and mean arterial pressure (MAP) were correlated with parameters of LV structure and function. Correlation coefficients were: SBP versus left ventricular mass index (LVMI), r = 0.246; SBP versus early diastolic mitral annular velocity (MAV), r = −0.179; DBP versus LVMI, r = 0.199; DBP versus MAV, r = −0.199; MAP versus LVMI, r = 0.276; and MAP versus MAV, r = −0.206, all with P < .05. However, neither capacitative nor reflective arterial compliance was significantly correlated with any parameter of LV structure and function. After controlling for age and 10 cardiovascular and metabolic risk factors, the correlation between blood pressure and the measured LV parameters was substantially unchanged, as was the lack of correlation between indices of arterial compliance and the LV indices. Arterial blood pressure is correlated with LV structure and function in the very elderly, but arterial stiffness, as measured by diastolic pulse contour analysis, is not. [Copyright &y& Elsevier]

Objectives: To examine the association of homocysteine with cognitive functioning in very elderly community-dwelling individuals (80 years or older). Methods: Two hundred twenty-eight nondemented community-dwelling individuals were assessed with a broad neuropsychological battery. Bloods were drawn to measure homocysteine, serum vitamin B12, and folate levels and APOE genotype. Results: Higher homocysteine levels were associated with poorer executive-language functioning scores (r = -0.311)- The association persisted when serum B12 and folate levels were controlled for (r = -0.308). Homocysteine levels were not associated with memory score (r = 0.120). Conclusions: In very elderly, nondemented community dwellers, high homocysteine levels are associated with poorer executive-language functioning but not with memory. This possible differential effect of homocysteine on cognitive functions suggests that it may affect only specific brain regions or mechanisms underlying healthy executive functioning. [ABSTRACT FROM AUTHOR]

Objective: To examine the association of cholesterol with cognitive functioning in oldest old community dwelling individuals with and without the apolipoprotein e4 (APOE4) allele. Method: One hundred eighty-five nondemented, community dwelling individuals (⩾85) were assessed with a broad neuropsychological battery. Bloods were drawn to assess total, low-density lipoprotein (LDL), and high-density lipoprotein cholesterol, as well as for APOE genotyping. Results: In contrast to our expectations, high total cholesterol and high LDL cholesterol were associated with higher memory scores for noncarriers of the APOE4 allele. No significant associations between cognitive performance and lipid profile were found for carriers of the APOE4 allele. Conclusions: In oldest old nondemented noncarriers of the APOE4 allele, high cholesterol is associated with better memory function. Further examination of the role of APOE genotype on the association between cholesterol and cognitive performance, especially in the oldest old is warranted. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to examine the association of religious education and observance with dementia among participants in the Israeli Ischemic Heart Disease study.Study Design and Setting: We assessed dementia in 1,890 participants among 2,604 survivors of 10,059 participants in the Israeli Ischemic Heart Disease study, a longitudinal investigation of the incidence and risk factors for cardiovascular disease among Jewish male civil servants in Israel. Face-to-face interviews were conducted with 651 subjects identified as possibly demented by the Modified Telephone Interview for Cognitive Status.Results: Of 1,628 subjects included in this analysis (mean age 82 at assessment), 308 (18.9%) had dementia. The prevalence rates of dementia (and odds ratios (ORs) relative to those with exclusively religious education, adjusted for age, area of birth, and socioeconomic status) were 27.1% for those with exclusively religious education, 12.6% (OR=0.49) for those with mixed education, and 16.1% (OR=0.76) for those with secular education. For religious self-definition and practice, the prevalence rates were 9.7%, 17.7%, 14.1%, 19.3%, and 28.8% for categories from least to most religious (ORs relative to the most religious: 0.43, 0.67, 0.48, 0.55).Conclusions: Examining lifestyles associated with religiosity might shed light onto environmental risks for dementia. Mechanisms underlying these associations remain elusive. [ABSTRACT FROM AUTHOR]

Self-injurious behavior in autism spectrum disorder (ASD) has been associated with lower whole blood serotonin levels and the role of serotonin transporter gene promoter region (5HTTLPR) polymorphisms is of interest because of their effects on transporter functioning. This study examined the association between self-injurious behavior in ASD and allelic frequencies of 5HTTLPR. Sixty-four children and adolescents with ASD who were not taking serotonergic medication at the time of the assessment were included in the analysis. Self-injury was assessed using the Autism Diagnostic Interview-Revised (ADI-R) and whole blood serotonin levels were measured using high-pressure liquid chromatography (HPLC) with fluorometic detection. DNA was extracted from saliva and PCR amplified with fluorescent primers. Self-injury significantly increased with the number of La alleles of the 5HTTLPR and decreased with the number of Lg alleles. Self-injury in ASD may be associated with a specific genotype of the serotonin transporter gene promoter region. Future studies should continue to explore subgroups to clarify the underlying clinical and genetic heterogeneity in ASD. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have documented that patients with schizophrenia show neurocognitive impairments, which are also heritable in schizophrenia families. In view of these findings, the current investigation tested the hypothesis that neurocognitive performance of schizophrenia probands can predict the neurocognitive performance of their unaffected family members. Methods: Participants (n=1967; schizophrenia=369; first-degree relatives=1072; community comparison subjects=526) in the Consortium on the Genetics of Schizophrenia were administered the Penn Computerized Neurocognitive Battery. Results: Consistent with prior work, probands showed significant neurocognitive impairment, and neurocognitive ability was significantly heritable across domains. On average, unaffected relatives did not differ from community comparison subjects in their neurocognitive performance. However, in six of seven domains, proband scores predicted the performance of their unaffected siblings. Male, but not female, proband performance was predictive of their unaffected relatives’ (siblings and mothers) performance, most consistently in face memory and spatial processing. Conclusions: Using a novel approach in which individual probands are paired with their respective unaffected relatives within each family, we found that male proband performance predicted both sister and brother performance, an effect that was most powerfully observed for face memory and spatial processing. Results suggest that the familial transmission of sexually dimorphic neurocognitive domains, in which a particular sex tends to show a performance advantage over the other, may not itself be sex specific in schizophrenia families. [Copyright &y& Elsevier]

Abstract: In order to investigate the nature of the eye tracking impairment in schizophrenia spectrum we measured pursuit gain with a constant velocity target using a quantitative (RMS error in pursuit gain) and, on an exploratory basis, a qualitative (quality of tracking) measure. We utilized a sample consisting of three clinically characterized groups: patients with schizophrenia (SZ), their first degree non-psychotic relatives, subjects with schizotypal personality disorder (SPD), and healthy volunteers (HV). Thirty three SZ patients, 19 SPD subjects, 66 non-psychotic relatives (all clinically assessed for schizophrenia spectrum psychopathology—DSM-IIIR) and 18 HV were evaluated using an infrared eye tracking system. Targets were constant velocity trapezoids at 5°/s (slow) and 16°/s (fast). The quality of the eye tracking was independently evaluated by at least two raters (ICC: 0.92). The RMS measures at the two velocities (quantitative measure) and the quality of the tracking obtained for each velocity were entered separately into a two factor repeated measures ANOVA, with velocity and diagnosis as the independent measures. For the quantitative ratings (RMS error), a significant effect for velocity was found, with all subjects performing worse at the higher velocity, but there was no significant velocity by diagnosis interaction. In addition, an overall significant effect for diagnosis was found in the four-group ANOVA. In post hoc multiple comparison tests, SZ subjects performed significantly worse from the HV and the relatives. SPD subjects were not different from patients with schizophrenia (or from any group—and their performance was intermediate between the HV and the SZ). Relatives of the patients with schizophrenia were different from SZ subjects, but not different from SPD or HV subjects. Similar results were obtained in the exploratory qualitative ratings. Clinical symptoms did not correlate significantly with quantitative or qualitative performance in any group. We have found that the performance of SPD subjects is intermediate between that of patients with schizophrenia and the healthy volunteers in both qualitative and quantitative (exploratory) measures. Indeed, SPD subjects comprise the only group not statistically different from schizophrenic patients in quantitative or qualitative ratings. [Copyright &y& Elsevier]

Abstract: Little is known about brain function in the oldest old, although this is the fastest growing segment of the population in developed countries and is of paramount importance in public health considerations. In this study, we investigated the cerebral response to a memory task in healthy subjects over age 90 compared with healthy younger elderly. We studied 29 healthy elderly subjects, 12 over age 90 and 17 between age 70 and 80. All subjects were cognitively intact, as verified by a neuropsychological battery, and performed a nonverbal memory task while undergoing a functional MRI (fMRI). Activation results were analyzed by a random-effects ANCOVA using SPM5. The task resulted in activation of similar areas of the posterior temporal, parietal, and posterior frontal cortexes, but the activation was more robust in the younger subjects, especially in the right hippocampus, and parietal and temporal cortices. This finding remained after controlling for education, cognition, task performance or cerebral atrophy. The phenomenon of relatively maintained performance, despite significant brain atrophy and lower activation is consistent with the cognitive reserve theory and may be specific to subjects with extremely successful aging. Further investigation of brain activation patterns in the oldest old is warranted. [Copyright &y& Elsevier]

Abstract: Objective: To examine the association between number of born children and neuropathology of Alzheimer''s disease (AD). Methods: The brains of 86 subjects with data on the number of biological children born, were studied postmortem. Primary analyses included 73 subjects (average age at death=80; 42 women) devoid of cerebrovascular disease associated lesions (i.e., infarcts) or of non-AD related neuropathology. Women were significantly older at death than men (85.6 vs. 73.4; p <.0005) but did not differ significantly from men in number of children or dementia severity. Secondary analyses included 13 additional subjects who had concomitant cerebrovascular disease. Density of neuritic plaques (NPs) and neurofibrillary tangles (NFTs) in the hippocampus, entorhinal cortex, amygdala and multiple regions of the cerebral cortex, as well as composites of these indices reflecting overall neuropathology, were analyzed. For men and women separately, partial correlations, controlling for age at death and dementia severity, were used to assess the associations of number of children with these neuropathological variables. Results: Among women, all the partial correlations were positive, with statistical significance for overall neuropathology (r =.37; p =.02), overall NPs (r =.36; p =.02), and for NPs in the amygdala (r =.47; p =.002). Among men, none of the partial correlations were statistically significant. Results of the secondary analyses were similar. Conclusions: Since the associations between number of children and neuropathology of AD were found for women only, they might reflect sex-specific mechanisms (such as variations in estrogen or luteinizing hormone levels) rather than social, economic, biological or other mechanisms common to both men and women. [Copyright &y& Elsevier]

Background: N100 evoked potential amplitude and gating abnormalities have been widely observed in schizophrenia patients. However, previous studies have been inconclusive as to whether similar deficits are present in unaffected family members. The Consortium on the Genetics of Schizophrenia (COGS) is a multisite National Institute of Mental Health (NIMH) initiative examining neurocognitive and neurophysiological measures as endophenotypes for genetic studies of schizophrenia. We report initial results from the COGS dataset of auditory N100 amplitude and gating as candidate endophenotypes. Methods: Evoked potential data were acquired from 142 schizophrenia probands, 373 unaffected first-degree relatives, and 221 community comparison subjects (CCS), using an auditory paired-click stimulation paradigm. Amplitude of the N100 response to each click and the click 2/click 1 ratio were dependent variables. Heritability was estimated based on kinships using Solar v.2.1.2. Group differences were examined after subjects were categorized as either “broad” or “narrow,” based on the presence (broad) or absence (narrow) of nonpsychotic psychiatric comorbidity. Results: Heritability estimates were .40 and .29 for click1 and click2 amplitudes and .22 for the ratio. Broad and narrow patients both had impaired click 1 amplitudes. Broad relatives, but not narrow relatives, exhibited similar impairments. There were no group differences for either click 2 amplitude or the gating ratio. Conclusions: N100 amplitude is a heritable measure that is abnormal in patients and a subset of relatives for whom psychiatric comorbidity may be a genetically associated phenotype. Auditory N100 gating, although heritable, is less viable as a schizophrenia endophenotype. [Copyright &y& Elsevier]

Abstract: Autism is predominantly genetically determined. Evidence supports familiality of the main sets of behavioral characteristics that define the syndrome of autism; however, possible non-genetic effects have also been suggested. The present study compared levels of autism symptom domains, as measured by the Autism Diagnostic Interview, and useful phrase speech scores between 106 pairs of first- and second-born siblings from multiply affected families. In addition, the intercorrelations between the measures were compared between siblings. The overall mean repetitive behavior total score was significantly higher (worse) in first-born than in second-born siblings. In contrast, first-born siblings had significantly lower (better) useful phrase speech than their younger siblings. Autism social and non-verbal communication scores were significantly correlated in first- and in second-born siblings. However, there was a significant difference in the coefficients between first- and second-born siblings. Performance on the non-verbal communication domain was also significantly and positively correlated with useful phrase speech score in both first- and second-born siblings. It is unclear at this time whether these results are of biologic origin. Nevertheless, the findings suggest that genetic studies in autism using specific levels of familial autism traits as phenotypes should take into account their intercorrelations and birth order effects embedded in the instrument. [Copyright &y& Elsevier]

Abstract: Impulsive behaviors, which can include aggression, substance use and suicide, are common and core features of the DSM Axis II Cluster B personality disorders. The construct of dispositional impulsivity is multidimensional and a number of self-report measures have been created to represent features of this trait (e.g., novelty seeking, behavioral disinhibition, nonplanning). Because these questionnaires are rarely administered together in the same sample, little is known about how they are related to one another. The current study was conducted to examine the structure of dimensional impulsive personality traits in a large normative sample (n =351). Analyses revealed that dispositional impulsivity was represented by three moderately correlated latent factors labeled thrill seeking, nonplanning and disinhibited behavior. Confirmatory factor analyses were also used to examine the extent to which the internal structure of these impulsive personality traits was similar in a sample defined as abnormal (i.e., DSM-III-R Cluster B PD diagnoses; n =70). Results revealed that the structure of these traits was consistent across the two samples in a model that constrained factor loadings and structural covariances (NFI=0.89; CFI=95; RMSEA=0.04). In addition, correlational relationships between the impulsivity factor scores and behavioral and sociodemographic factors (e.g., socioeconomic status, substance use) were consistent across the two samples. These results help to establish a common framework for understanding the multidimensional nature of impulsivity. Results from these analyses also lend support to a large body of work that demonstrates that normal and abnormal personality features are related. [Copyright &y& Elsevier]

Background: The serotonin transporter (5-HTT) has long been considered likely to play a role in autism. Hyperserotonemia has been consistently found in a proportion of autistic patients, and the use of selective serotonin reuptake inhibitors (SSRIs) can have a positive effect in treating some symptoms of autism. Specific variants of the 5-HTT gene, SLC6A4, especially the insertion–deletion 5-HTTLPR promoter locus, have been found to modulate its expression and transporter function. Methods: We examined the transmission of the short or long allele of 5-HTTLPR locus to affected individuals, using a large cohort of 352 families. In addition, we screened five single nucleotide polymorphisms (SNPs) in the 5′ region of SLC6A4 previously reported to be positively associated with autism, as well as 4 additional SNPs also in the 5′ region. Results: No association of the 5-HTTLPR locus with autism was found. Furthermore, no evidence for association of any of the nine SNPs covering the SLC6A4 gene, or any of their haplotypes, was observed in our study. Using obsessive–compulsive behaviors (OCB), severe OCBs or rigid–compulsive subsets of our cohort gave the same negative results. Conclusions: SLC6A4 variants do not appear to be significantly involved in the liability to autism. [Copyright &y& Elsevier]

Abstract: Many studies have found that individuals with schizophrenia have been born in winter months in disproportionately high numbers. Temperature and weather effects, such as hot summers or cold winters, have been among the suggested explanations for this seasonality effect. We studied the relationship between schizophrenia and season of birth in Puerto Rico, a tropical island with mild seasonal variation of temperature and virtually no cold periods. Our sample consisted of 132 subjects (57 with schizophrenia, 75 without) from 24 multiplex families. Schizophrenic family members were significantly more likely to be born during the winter months (21/57; 36.8%) than their unaffected relatives (16/75; 21.3%). These results suggest that extreme temperatures are not a sufficient explanation for the seasonality effect and that other factors associated with seasonality may have an effect on the later development of schizophrenia. The fact that a seasonality effect was found in a group likely to have an increased genetic loading for schizophrenia suggests that seasonality may be associated with a second, environmental “hit” in a “two-hit hypothesis” of schizophrenia. [Copyright &y& Elsevier]

Abstract: Objectives: The study aimed to evaluate the feasibility and discomfort of magnetic resonance imaging (MRI) procedures in the oldest-old subjects (age>90 years) using a survey design in a university-affiliated neuroimaging research center. Participants: Forty-one community-dwelling, elderly subjects were considered for participation. Twenty-nine of them underwent voluntary, extensive MRI scanning (up to 1 h) as part of a project on brain function in the oldest old. Thirteen oldest old (OO, range 90–93 years, mean 92 years) were compared to 16 young old (YO, range 72–80 years, mean 76 years). Measurements: Likert-style questionnaire on satisfaction following extensive MRI scanning session (up to 1 h) was administered. Data were analyzed by an analysis of variance (gender by age group). Results: All subjects reported positive experiences with no significant difficulties or concerns. There were minor differences in some rated items, with the OO and males slightly less comfortable than YO and females, respectively. Overall, the OO tolerated the procedures as well as the YO. Conclusion: Very long MRI sessions are feasible, even in the oldest-old subjects, and are not associated with any significant discomfort. Prior screening and thorough education of the subjects probably help to minimize anxiety and dropout. [Copyright &y& Elsevier]

Parents of autistic probands with high and low rates of repetitive behaviors were compared for rates of obsessive–compulsive traits and disorder. The rate of repetitive behaviors was assessed using the Autism Diagnostic Interview-Revised (ADI-R) in 176 autistic probands from 57 multiplex families. Obsessive–compulsive disorder (OCD) in parents was determined by direct interview using a parental history questionnaire, with screening for obsessive–compulsive traits using the Yale-Brown Obsessive–Compulsive Scale checklist. Children who had high total scores on the repetitive behavior domain of the ADI-R were significantly more likely to have one or both parents with obsessive–compulsive traits or disorder compared with children who had low total scores on this domain. Children with high scores on D1/D2 of the ADI-R (narrow restricted interests and rituals) were significantly more likely to have one or both parents with OCD, especially fathers, than those with low D1/D2. The occurrence of obsessive–compulsive traits or disorder in parents of autistic children in multiplex families is significantly more likely if autistic children have a high occurrence of repetitive behaviors. Dichotomizing autistic probands by severity and type of repetitive behaviors (circumscribed interests and compulsive rituals) may yield more homogenous groups, which could be helpful in genetic linkage studies. [Copyright &y& Elsevier]

: BackgroundIndividuals with schizotypal personality disorder (SPD) share cognitive deficits with schizophrenic patients, suggesting that these deficits represent a core feature of the schizophrenia spectrum. We investigated the neuropsychological profile in SPD patients compared with two comparison groups: healthy volunteers (HV) and patients who met criteria for another non-schizophrenia spectrum personality disorder (NSS).: MethodsWe tested 48 DSM-III-R SPD patients, 22 NSS and 32 HV on a neuropsychologic battery that included the California Verbal Learning Test (CVLT), Trail Making A and B, the DOT test of working memory, the Stroop Color–Word Interference, the Paced Auditory Serial Addition Test (PASAT), the Wechsler Memory Scale Visual Reproduction Test (WMSV–R), and the Wechsler Adult Intelligence Scale vocabulary and block design.: ResultsNormative standards for performance were created using the HV group. SPD patients performed significantly worse compared with HVs; specifically, SPD patients demonstrated impaired performance on the PASAT and the WMSV–R immediate and delayed recall compared to HV. Moreover, SPD patients were impaired in the PASAT and the WMSV–R immediate condition compared with the NSS group. The NSS patients did not differ from HV on any of the cognitive tasks. The interpersonal factor of the schizotypal symptoms inversely correlated with the PASAT score (r = −.32, p < .006).: ConclusionsCompared with HVs, SPD patients demonstrate modest cognitive impairment. These differences reached statistical significance for the PASAT (an auditory working memory task), and the WMSV–R immediate and delayed recall (a learning–recall test). In contrast, performance of NSS patients did not differ from that of HVs. The types of deficits observed in SPD patients are qualitatively similar to but milder than those seen in patients with schizophrenia. [Copyright &y& Elsevier]