Teresa Lee

Treatment of obsessive-compulsive disorder by psychosurgery

We report a longitudinal study of 26 patients with medically intractable obsessive‐compulsive disorder (OCD) who were treated with psychosurgery and had a comprehensive follow‐up for a mean 10 years. Seventeen patients had combined orbitomedial and cingulate lesions, 6 cingulate lesions only and 3 orbitomedial lesions only. Eighteen patients were interviewed personally and lesions verified on magnetic resonance imaging scans in fourteen. On a 6‐point global rating scale, 10 (38%) patients had obvious improvement, another 6 (23%) showed mild improvement of doubtful clinical value, and the remaining 10 showed either no change (n= 6; 23%) or were judged to be worse (n= 4; 15%). Both obsessive and compulsive symptoms improved, and this change was independent of the changes in anxiety and depression scores. No significant predictors of improvement were identified. Patients with cingulate lesions only fared worse. Eight patients who had a second operation did not show much improvement. A comparison of a subgroup of patients with 10 matched nonsurgical OCD controls supported the contention that the improvement in OCD was attributable to the psychosurgery. Important adverse effects in the stereotactic surgery group (n= 20) were epilepsy (1 patient) and personality change (2 patients). The psychosurgery group performed relatively poorly on the Wisconsin Card Sort Test but did not show any deterioration in Wechsler Intelligence and Memory scores.

Genetic influences on cognitive functions in the elderly: a selective review of twin studies.

In this review, we examined the published reports on the heritability of cognitive functioning in old age. Twenty-four papers from five study centers, comprising of participants with a mean age of 65 years and above were examined. The comparability of findings from different studies was compromised by the use of different measures for the same cognitive domain, and with large scale twin studies in cognitive aging limited to a few Scandinavian countries. While the results from cross-sectional samples appear to lend support for the notion that heritability of cognitive functions decreases in the elderly, the findings are best considered inconclusive. Longitudinal reports show little evidence for genetic effects, but an increase in unique environmental influences on the rate of cognitive change as age increases. In relation to the two prominent theories of cognitive aging, the genetic influence on processing speed as a major contributor to cognitive aging has been indicated in three reports, whereas the genetic relationship between executive functions and other cognitive functions has not been explored. Only two studies have focused on sex difference and did not find sex-specific genetic influence in cognitive abilities. This review indicates that there are complex relationships between heritability, environmental influence, and cognitive functions in the elderly. It highlights the need for more research, with consistent and appropriate cognitive measures, with data obtained from larger and more geographically and culturally diverse twin samples.

Genetic influences on four measures of executive functions and their covariation with general cognitive ability: the Older Australian Twins Study.

Abstract“Executive functions” (EF) is a multidimensional construct which encompasses many higher-order cognitive control operations, and is considered a potential mediator of age-associated changes in other cognitive domains. Here we examine the heritability of four measures of EF, and the genetic influences on their covariation with general cognitive abilities (GCA) from the Older Australian Twins Study. Participants included 117 pairs of monozygotic twins, 98 pairs of dizygotic twins, and 42 single twins, with a mean age of 71. Genetic modeling showed that additive genetic factors contributed to 59, 63, 29, and 31% of the variance in the four measures: working memory, verbal fluency, response inhibition and cognitive flexibility, respectively. The phenotypic associations among the four EF measures were modest, which is in line with other evidence that EF is a multi-dimensional construct. All of the covariation between the EF measures was attributable to a common genetic factor. Similarly, all of the covariation between EF and General Cognitive Ability was explained by a common genetic factor, with no significant covariance due to environmental (E) factors. The genetic correlations between the measures were moderately high, suggesting that they may have common biological underpinnings. The genetic influence in the covariation of the EF measures and GCA also suggests that some aspects of EF and GCA share the same genes or same set of genes.

A comprehensive neuropsychiatric study of elderly twins: The Older Australian Twins Study

The Older Australian Twins Study (OATS) was recently initiated to investigate genetic and environmental factors and their associations and interactions in healthy brain ageing and ageing-related neurocognitive disorders. The study extends the classic MZ-DZ design to include one or two equivalently aged siblings for each twin pair and utilizes the rich resources of the Australian Twin Registry. The study has a number of distinguishing features including comprehensive psychiatric, neuropsychological, cardiovascular, metabolic, and neuroimaging assessments, a longitudinal design and links with a brain donor program. The study measures many behavioral and environmental factors, but in particular lifetime physical and mental activity, physical and psychological trauma, loss of parent early in life, later losses and life events, early-life socioeconomic environment, alcohol and drug use, occupational exposure, and nutrition. It also includes comprehensive cardiovascular assessment, blood biochemistry, genetics and proteomics. The socio-demographic and health data on the first 172 pairs of twins participating in this study are presented. Prevalence of mild cognitive impairment is 12.8% and of dementia 1.5% in the sample. The target sample size is 1000, with at least 400 pairs of twins aged 65-90 years. The cohort will be assessed every two years, with in-depth assessments being repeated. OATS offers an excellent opportunity for collaboration with other similar studies as well as researchers who share the same interests.

Neuropsychological Outcome from Psychosurgery for Obsessive-Compulsive Disorder

Seventeen obsessive-compulsive disorder patients treated with psychosurgery were administered a comprehensive neuropsychological test battery. Their performance on neuropsychological testing was compared with that of an age and severity matched sample of 17 OCD sufferers who had not received psychosurgery. The psychosurgery and control groups did not differ in intellectual or memory functioning, consistent with earlier findings that psychosurgery does not reduce global ability estimates. The psychosurgery group performed more poorly than the control group on an adaptation of the Wisconsin Card Sorting Test, demonstrating the possible impact of frontal lobe lesions on the abilities underpinning the formation and shifting of response sets.

A review of different methods of assessing social cognitive function in clinical settings.

PURPOSE OF REVIEW Social cognition refers broadly to the way in which we process social information, and is a critical predictor of social competency. This article provides an overview of some of the assessment approaches that have been developed to assess this construct. RECENT FINDINGS A variety of well validated assessment approaches are now available. The most frequently used methods index explicit emotion recognition and/or mental state attribution. There has also been an increasing emphasis on the need to better understand the role of specific perceptual features and cognitive task demands in social cognitive difficulties. SUMMARY In the past 20 years, research on social cognitive function has grown exponentially, reflecting an increased recognition that social cognitive skills are critical for communicative discourse, and in turn mental health and well-being. Accordingly, a large number of measures are now available to quantify social cognitive function. This review shows that many of these measures have good psychometric properties, and appear to have at least moderate sensitivity. However, the review also highlights the importance of using appropriate control tasks to assess the specificity of any observed social cognitive failures, as well as the need for the continued development of measures with greater ecological validity.Purpose of review Social cognition refers broadly to the way in which we process social information, and is a critical predictor of social competency. This article provides an overview of some of the assessment approaches that have been developed to assess this construct. Recent findings A variety of well validated assessment approaches are now available. The most frequently used methods index explicit emotion recognition and/or mental state attribution. There has also been an increasing emphasis on the need to better understand the role of specific perceptual features and cognitive task demands in social cognitive difficulties. Summary In the past 20 years, research on social cognitive function has grown exponentially, reflecting an increased recognition that social cognitive skills are critical for communicative discourse, and in turn mental health and well-being. Accordingly, a large number of measures are now available to quantify social cognitive function. This review shows that many of these measures have good psychometric properties, and appear to have at least moderate sensitivity. However, the review also highlights the importance of using appropriate control tasks to assess the specificity of any observed social cognitive failures, as well as the need for the continued development of measures with greater ecological validity.

Leisure Activity, Health, and Medical Correlates of Neurocognitive Performance Among Monozygotic Twins: The Older Australian Twins Study

OBJECTIVES We aimed to examine associations between each of three leisure activities (Cognitive, Physical, and Social) and performance in selected cognitive domains (Speed, Memory, Verbal ability, and Executive functions) and global cognition. We also aimed to explore associations between medical and health factors and late-life cognition. METHOD Our sample comprised 119 pairs of monozygotic twins from the Older Australian Twins Study. Their mean age was 71 years and 66% were women. We used a discordant co-twin design, with cognitive performance measures as dependent variables and leisure activities as independent variables. Multiple regression analyses were performed, adjusting for potentially relevant medical and health factors. RESULTS Discordance in Cognitive Activity and Social Activity participation was positively associated with discordance in performance on some cognitive domains. There were no associations between Physical Activity participation and cognition. Discordance in several cardiovascular, frailty, and sensory variables was associated with discordance in cognitive performance measures. DISCUSSION This study identified lifestyle and health-related influences on late-life cognition. Our findings not only help in understanding the neurobiological mechanisms, they also have practical implications for interventions to prevent or slow age-related cognitive decline.

The contribution of twins to the study of cognitive ageing and dementia: The Older Australian Twins Study

Abstract The Older Australian Twins Study (OATS) is a major longitudinal study of twins, aged ≥ 65 years, to investigate genetic and environmental factors and their interactions in healthy brain ageing and neurocognitive disorders. The study collects psychiatric, neuropsychological, cardiovascular, metabolic, biochemical, neuroimaging, genomic and proteomic data, with two-yearly assessments, and is currently in its third wave. The initial cohort comprises 623 individuals (161 monozygotic and 124 dizygotic twin pairs; 1 MZ triplets; 27 single twins and 23 non-twin siblings), of whom 426 have had wave 2 assessment. A number of salient findings have emerged thus far which assist in the understanding of genetic contributions to cognitive functions such as processing speed, executive ability and episodic memory, and which support the brain reserve hypothesis. The heritability of brain structures, both cortical and subcortical, brain spectroscopic metabolites and markers of small vessel disease, such as lacunar infarction and white matter hyperintensities, have been examined and can inform future genetic investigations. Work on amyloid imaging and functional magnetic resonance imaging is proceeding and epigenetic studies are progressing. This internationally important study has the potential to inform research into cognitive ageing in the future, and offers an excellent resource for collaborative work.

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals.

The variability of episodic memory decline and hippocampal atrophy observed with increasing age may partly be explained by genetic factors. KIBRA (kidney and brain expressed protein) and CLSTN2 (calsyntenin 2) are two candidate genes previously linked to episodic memory performance and volume of the hippocampus, a key memory structure. However, whether polymorphisms in these two genes also influence age-related longitudinal memory decline and hippocampal atrophy is still unknown. Using data from two independent cohorts, the Sydney Memory and Ageing Study and the Older Australian Twins Study, we investigated whether the KIBRA and CLSTN2 genetic polymorphisms (rs17070145 and rs6439886) are associated with episodic memory performance and hippocampal volume in older adults (65-90 years at baseline). We were able to examine these polymorphisms in relation to memory and hippocampal volume using cross-sectional data and, more importantly, also using longitudinal data (2 years between testing occasions). Overall we did not find support for an association of KIBRA either alone or in combination with CLSTN2 with memory performance or hippocampal volume, nor did variation in these genes influence longitudinal memory decline or hippocampal atrophy in two cohorts of older adults.

Cognitive functioning in older twins: The Older Australian Twins Study

Aim:  To examine the concordance rates of common medical conditions and neurocognitive performance in monozygotic (MZ) and dizygotic (DZ) older twins.