The possible medicinal use of cannabinoids for chronic diseases emphasizes the need to understand the long-term effects of these compounds on the central nervous system. We provide a quantitative synthesis of empirical research pertaining to the non-acute (residual) effects of cannabis on the neurocognitive performance of adult human subjects. Out of 1,014 studies retrieved using a thorough search strategy, only 11 studies met essential a priori inclusion criteria, providing data for a total of 623 cannabis users and 409 non- or minimal users. Neuropsychological results were grouped into 8 ability domains, and effect sizes were calculated by domain for each study individually, and combined for the full set of studies. Using slightly liberalized criteria, an additional four studies were included in a second analysis, bringing the total number of subjects to 1,188 (i.e., 704 cannabis users and 484 non-users). With the exception of both the learning and forgetting domains, effect size confidence intervals for the remaining 6 domains included zero, suggesting a lack of effect. Few studies on the non-acute neurocognitive effects of cannabis meet current research standards; nevertheless, our results indicate that there might be decrements in the ability to learn and remember new information in chronic users, whereas other cognitive abilities are unaffected. However, from a neurocognitive standpoint, the small magnitude of these effect sizes suggests that if cannabis compounds are found to have therapeutic value, they may have an acceptable margin of safety under the more limited conditions of exposure that would likely obtain in a medical setting. (JINS, 2003, 9, 679–689.)

In this study we examined the independent and interactive effects of lifetime patterns of drinking and smoking on cognitive performance in elderly African Americans. A sample of 230 individuals with varying histories of alcohol and cigarette use was drawn from the Hillsborough Elder African American Life Study, a community-based, cross-sectional study of older adults aged 60 to 84. Dependent variables were the results of a neuropsychological battery that provided measures of general cognitive ability, executive function, and memory. Specifically, our study addressed (1) whether individuals with a lifetime history of sustained smoking and/or drinking show lower levels of cognitive performance in comparison to lifetime abstainers, (2) whether cumulative lifetime doses of alcohol or cigarettes, or of the two substances in interaction, have an effect on cognition, and (3) whether individuals who have histories of periodic, intense use of either alcohol or cigarettes show lower levels of cognitive performance in comparison to lifetime abstainers. When significant results were obtained, effect sizes were small, not exceeding 5% of the variance. A single exception occurred for the intensity analyses, in which drinking explained approximately 16% of the variance in global cognitive ability after adjusting for the contributions of control variables. In these analyses, drinking was found to have a U-shaped effect on global cognitive ability and total acquisition in the memory trials. Specifically, moderate users performed at a lower level than abstainers or heavy users, who did not differ from each other. (JINS, 2003, 9, 690–697.)

Patients with dementia, particularly those with frontotemporal dementia (FTD), are reported to display marked negative symptoms, including apathy, lack of initiative, and flattened affect, similar to those observed in schizophrenic patients. However, negative symptoms have yet to be formally quantified in an FTD population. Twenty-seven patients with FTD (11 primarily right-sided, 8 primarily left-sided, and 4 symmetric) and 7 patients with Alzheimer's disease were rated on the Scale for the Assessment of Negative Symptoms, the Positive and Negative Syndrome Scale, and the Emotional Blunting scale. The FTD patients registered significantly more negative symptoms than the Alzheimer's patients, averaging a threefold increase; groups did not significantly differ in positive symptoms. Negative symptom scale scores were negatively correlated with nonverbal executive skills (23–44% shared variance), verbal executive skills (up to 25% shared variance) and verbal memory (up to 20% shared variance), but were unrelated to measures of attention, verbal and nonverbal information processing, nonverbal memory, language, and constructional skill. In contrast, positive symptoms were positively correlated with constructional skill (19% shared variance) and attentional scores (15% shared variance). These findings add to the existing literature relating negative symptoms to anterior cerebral hypofunction, and suggest that positive symptoms, at least in this population, may be tied to increased posterior activation. (JINS, 2003, 9, 698–709.)

A referred cohort of 67 clinically defined PPA patients were compared to 99 AD patients with formal language and nonverbal cognitive tests in a case control design. Language fluency was determined at the first and last follow up visits. Quantitation of sulcal and ventricular atrophy on MRI was carried out in 46 PPA and 53 AD patients. Most PPA patients (57%) are relatively fluent when first examined. Visuospatial and memory functions are initially preserved. Aphemic, stuttering, “pure motor” presentation, or agrammatic aphasia are seen less frequently. Later most PPAs become logopenic and nonfluent, even those with semantic aphasia (dementia). In contrast, AD patients were more fluent and had relatively lower comprehension, but better overall language performance. MRI showed significant left sided atrophy in most PPA patients. Subsequent to PPA, 25 patients developed behavioral manifestations of frontotemporal dementia and 15 the corticobasal degeneration syndrome, indicating the substantial clinical overlap of these conditions. Language testing, particularly fluency scores supported by neuroimaging are helpful differentiating PPA from AD. The fluent–nonfluent dichotomy in PPA is mostly stage related. The aphemic-logopenic-agrammatic and semantic distinction is useful, but the outcomes converge. (JINS, 2003, 9, 710–719.)

Test scores from a comprehensive neuropsychological battery administered to 1602 subjects consisting of 1347 subjects with probable Alzheimer's disease (AD), 100 subjects with questionable dementia (QD) and 155 non-demented elderly control subjects were cross-sectionally analyzed. Subjects with probable AD were categorized as mild (n = 244), moderate (n = 480), severe (n = 376), and very severe (n = 247) according to modified mini mental status exam (mMMSE) scores. Mean scores on individual neuropsychological tests are provided for each group of subjects. Stratified random sampling was performed to select a sample of mild AD subjects who were matched in age and education to non-demented elderly controls, and analyses focused on the performance of QD subjects and mild AD subjects, whose scores were compared to those of the elderly control subjects. Selected scores were organized by cognitive domain and logistic regressions were used to determine the domains and individual tests within each that were most predictive of group status. Results suggested a profile of scores associated with QD and mild AD including impaired recall of verbal information for both groups. Areas of lower functioning in QD subjects as compared to elderly controls included category fluency and visuospatial ability. (JINS, 2003, 9, 720–732.)

It is well established that some individuals with temporal lobe epilepsy (TLE) demonstrate language deficits at the single word level. However, discourse production rarely has been examined quantitatively within this group. This study compared adult TLE patients with an early seizure onset (≤ age 14 years, n = 27) to a control group (n = 28) on narrative and procedural discourse tasks. As a group, the TLE patients performed normally on the procedural discourse task, but differed significantly from the controls on several narrative discourse variables. At the individual level, 30% of the TLE patients versus 4% of the controls demonstrated impaired discourse ability (p < .01). Within this early onset TLE group, discourse performance was not associated with demographic or seizure history variables. Considering the cognitive domain, discourse performance correlated significantly with working memory. In summary, mild discourse dysfunction was present in a significant minority of early onset TLE patients, but this deficit was not closely associated with other language measures. Discourse ability and its neuropsychological, neuroanatomical and conversational speech correlates deserve further study in TLE patients. (JINS, 2003, 9, 733–739.)

Performance on long delays of delayed response tasks is associated with medial temporal function, a region of the brain affected by severe hypoglycemia. A previous study showed that children with type 1 diabetes mellitus (T1DM) with higher risk for severe hypoglycemia performed worse than controls on long delays of a spatial delayed response (SDR) task. We tested the more specific hypothesis that frequency of severe hypoglycemia would relate to long delay SDR performance. Children with T1DM (n = 51) and controls (n = 32) performed the SDR task with short and long delays. Information was collected on children's past severe hypoglycemia. In children with T1DM, number of past severe hypoglycemic episodes accounted for a significant portion of the variance in long delay SDR after controlling for age and age of onset. This relationship was not seen with short delay SDR or with other tasks (verbal or object memory, attention, motor speed). These results support the hypothesis that severe hypoglycemia has specific, negative effects on memory skills in children. If this relationship is extrapolated to children with higher frequency of severe hypoglycemia, due to longer duration of disease or poorer glucose control, it may affect daily functioning and thus need to be considered in treatment decisions. (JINS, 2003, 9, 740–750.)

The relationship between apolipoprotein E (apoE) genotype and cognitive performance was examined in 200 patients with probable Alzheimer's disease (AD). Differences between composite measures of verbal and nonverbal functioning were used to define asymmetric patterns of cognition. Patients who were homozygous for apoE ε4 demonstrated relatively worse nonverbal as compared to verbal cognitive ability. In contrast, participants who were heterozygous for apoE ε4 or who possessed no ε4 allele demonstrated relatively equivalent verbal and nonverbal cognitive abilities. Although age and dementia severity also contributed to these patterns, apoE genotype appears to have a significant unique contribution to cognitive performance in these individuals. The ε4 allele may thus be associated with a specific neurocognitive phenotype among patients with AD, with the overall pattern of cognitive asymmetry dependent upon ε4 dose. (JINS, 2003, 9, 751–759.)

While neurobiological factors are known to play a role in human aggression, relatively few studies have examined neuropsychological contributions to propensity for violence. We previously demonstrated cognitive deficits among men who committed domestic violence (batterers) compared to non-violent controls. Batterers had deficits in verbal ability, learning and executive problem-solving ability. These findings led us to examine whether executive control problems involving impulsivity contribute to problems with behavioral control among batterers, and to further examine their deficits in verbal functioning. Batterers (n = 41) enrolled in a domestic violence program were compared to 20 non-violent men of similar age, education, and socioeconomic background on neuropsychological tests of executive functioning, including impulsivity. Questionnaires and structured clinical interviews were used to assess emotional distress, aggression and self-reported impulsivity. Batterers showed greater impulsivity compared to non-batterers on several neuropsychological measures. Yet, the severity of these deficits was relatively mild and not evident in all batterers. Consistent with our previous findings, significant verbal deficits were again observed among the batterers. These findings suggest that while impulsivity may be a factor associated with domestic violence, it probably is not the sole determinant of the strong relationship between cognitive functioning and batterer status that we previously observed. Both verbal expressive deficits and behavioral impulsivity appear to be relevant variables in predisposing men to domestic violence. (JINS, 2003, 9, 760–770.)

The effect of the degree of illiteracy (complete or incomplete) on phonological skills, verbal and visual memory and visuospatial skills is examined in 97 normal Brazilian adults who considered themselves illiterate, and 41 Brazilian school children aged 7 to 8 years, either nonreaders or beginning readers. Similar literacy effects were observed in children and in adults. Tasks involving phonological awareness and visual recognition memory of nonsense figures distinguish the best nonreaders and beginning readers. Children performed better than adults at oral repetition of short items and figure recall, and adults better than children at semantic verbal fluency, digit span, and word list recall. A principal component analysis of the correlations between tasks showed that phonological awareness/ reading, phonological memory/oral repetition, and semantic verbal memory/fluency tasks, generated different components. The respective role of culturally based preschool activities and literacy on the cognitive functions that are explored in this study is discussed. (JINS, 2003, 9, 771–782.)

The profiles of neuropsychological deficits associated with Alzheimer's disease (AD) in Young-Old (M age < 70) and Very-Old (M age > 80) patients were compared, along with possible modifying effects of apolipoprotein E (APOE) genotype on these profiles. A comprehensive battery of neuropsychological tests was administered to the two AD patient groups (Young-Old: n = 33; Very-Old: n = 48) and their respective age-matched normal control (NC) groups who remained free of dementia on follow-up examinations over a 1 to 10 year period (Young-Old: n = 43; Very-Old: n = 36). AD and NC groups did not differ in education levels or gender distributions. Young-Old AD and Very-Old AD groups were comparable in education, gender, dementia severity, and disease duration. Results showed that both AD groups achieved comparable raw scores on all the neuropsychological measures. However, when scores were standardized on the basis of performance of their respective NC groups (i.e., age-corrected z scores), Very-Old AD patients significantly outperformed Young-Old AD patients on tests of executive functions, visuospatial skills, and delayed memory. Furthermore, the relationship between age and memory and executive function deficits in AD was modified by APOE genotype. These data suggest that the profile of neuropsychological deficits associated with AD in the Very-Old lacks the disproportionate saliency of episodic memory and executive function deficits typical of the Young-Old. (JINS, 2003, 9, 783–795.)

Findings of category-specific impairments have suggested that human semantic memory may be organized around a living/nonliving dichotomy. In order to assess implicit memory performance for living and nonliving concepts, one group of neurologically intact individuals participated in a cross-form conceptual priming paradigm. In Block 1, pictures primed words while in Block 2 words were used to prime pictures. Across all phases of the experiment, subjects decided whether items represented something which was living or nonliving, and response times were recorded. Results revealed greater priming for living concepts across both blocks. Greater priming for living concepts may have occurred because of increased or prolonged conceptual activation of these concepts. Results are discussed in the context of theoretical accounts of the category-specific impairments observed in brain-damaged populations. (JINS, 2003, 9, 796–805.)

We present the case of a 23-year-old Vietnamese male with a 2-year history of a psychotic illness marked by prominent negative symptoms, fatuousness and disturbed behavior. Neuroimaging revealed a prominent vascular flow void affecting the middle and anterior cerebral arteries, with associated increased collateral supply to the frontal cortex, consistent with Moyamoya disease. Neurological examination was unremarkable; however, neuropsychological assessment revealed significant executive dysfunction, including stimulus-driven behavior. Whilst the diagnosis of schizophrenia and Moyamoya disease may be coincidental, an interaction between the 2 diseases may have led to some of the atypical features of this case, including prominent executive dysfunction and marked sensitivity to psychotropic medication. We discuss the nature of possible interactions between the 2 conditions. This case also highlights the importance of re-evaluating patients with atypical or treatment-resistant psychoses for cerebral pathology. (JINS, 2003, 9, 806–810.)

The Journal of the International Neuropsychological Society published recently a paper that should become influential shortly. However, given its potential impact, this study has to be examined carefully.

We were pleased by Dr. Bruyer's opinion that our paper is likely to become “influential shortly” and welcome this opportunity to respond to his thoughtful comments and cautions regarding the manuscript. We certainly agree with his view that novel manuscripts and approaches must be examined carefully and appreciate his careful examination of our manuscript. Dr. Bruyer raises three qualifications related to our analyses and interpretation of the data.