Cognitive correlates of human brain aging: a quantitative magnetic resonance imaging investigation.

The relations between age-related changes in brain structure and neuropsychological test performance in 320 elderly nonclinical volunteers (ages 66-90) were examined by using quantitative MRI data and measures of attention, information processing speed, language, memory, and visuospatial ability. Final path analyses revealed significant brain-behavior relationships for two of the six cognitive measures: the Trail Making Test part B and visual delayed memory. Poorer performance on Trails B was associated with smaller cerebral hemisphere volumes and larger volumes of peripheral CSF, lateral ventricles, and third ventricle. Poorer recall on visual delayed memory was associated with larger volumes of the lateral ventricles and third ventricle. The findings demonstrate a relationship between age-related changes in brain structure and an age-related decline in attention, psychomotor speed, and visual delayed memory. The neurobiological basis for this relationship requires further investigation.

The use of herbal alternative medicines in neuropsychiatry. A report of the ANPA Committee on Research.

Growing numbers of people throughout the United States (40% in 1998) are using various forms of alternative therapies. A MEDLINE literature search of journals from the past three decades and an Internet database query were performed to determine the types and frequency of alternative therapies used, with special attention given to the herbal medicines used in neuropsychiatric disorders. Clinical effects, mechanisms of action, interactions, and adverse reactions of the herbal treatments are detailed. Objective controlled trials will be needed to establish safety and efficacy of herbal supplements. Knowledge of the properties of these therapies can improve the care of neuropsychiatric patients.

Prediction of the utility of a switch from unilateral to bilateral ECT in the elderly using treatment 2 ictal EEG indices.

BACKGROUND: The choice of whether to administer nondominant unilateral (UL) or bilateral (BL) ECT remains controversial. METHODS: A study in which moderately suprathreshold UL nonresponders at treatment 6 were randomized to UL or BL ECT offered the opportunity to explore whether ictal EEG indices at treatment 2 might predict response to UL ECT, and also which UL ECT nonresponders are likely to respond to BL ECT. RESULTS: We found that less postictal suppression in response to the second UL ECT stimulus was predictive of a poorer subsequent therapeutic response to UL ECT, but of a better therapeutic response if switched to BL ECT. A multivariate ictal EEG model was developed that had a significant capacity to differentiate those who will respond to UL ECT versus those who will not respond to UL ECT, but who will be therapeutic responders when switched to BL ECT. CONCLUSIONS: This study raises the possibility that ictal EEG indices at treatment 2 may identify situations when UL ECT is physiologically and therapeutically inadequate, and when BL ECT is likely to be more effective. The determination of whether such predictive physiologic models are of clinical utility for the prediction of outcome awaits further study.

Relation of education to brain size in normal aging: implications for the reserve hypothesis.

OBJECTIVE: To examine the relations between education and age-related changes in brain structure in a nonclinical sample of elderly adults. BACKGROUND: Education may protect against cognitive decline in late life--an observation that has led to the "reserve" hypothesis of brain aging. Little is known, however, about the effect of education on age-related changes in brain structure. METHODS: Quantitative MRI of the brain was performed in 320 elderly volunteers (age range, 66 to 90 years) living independently in the community (Mini-Mental State Examination scores > or =24), all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images using computer-assisted edge detection and trace methodology. High measurement reliabilities were obtained. RESULTS: Regression analyses (adjusting for the effects of intracranial size, sex, age, age-by-sex interactions, and potential confounders) revealed significant main effects of education on peripheral (sulcal) CSF volume-a marker of cortical atrophy. Each year of education was associated with an increase in peripheral CSF volume of 1.77 mL (p<0.03). As reported previously, main effects of age (but not education) were observed for all of the remaining brain regions examined, including cerebral hemisphere volume, frontal region area, temporoparietal region area, parieto-occipital region area, lateral (Sylvian) fissure volume, lateral ventricular volume, and third ventricle volume. CONCLUSIONS: The authors' findings demonstrate a relation between education and age-related cortical atrophy in a nonclinical sample of elderly persons, and are consistent with the reserve hypothesis as well as with a small number of brain imaging studies in patients with dementia. The neurobiological basis and functional correlates of this education effect require additional investigation.

Pharmacologic efficacy in neuropsychiatry: a review of placebo-controlled treatment trials. A report of the ANPA Committee on Research.

Psychiatric disorders frequently compound the disability and complicate the management of neurologic conditions. These disorders result in increased morbidity for the person afflicted, stress for the caregiver, and financial burden. This study reviews the randomized double-blind placebo-controlled pharmacologic treatment trials of psychosis, depression, anxiety, and agitation in neurologic conditions from 1966 to 1998. Ten studies involving psychosis, 13 involving depression, and 20 involving anxiety-agitation meeting the committee's criteria were identified. Relatively few randomized double-blind placebo-controlled pharmacologic treatment trials of psychiatric disorders complicating neurologic disease have been conducted. These trials do not strongly support one specific pharmacologic approach to treatment. Further study of newer psychotropic agents, augmentation strategies, and novel use of other agents may help improve the treatment of psychiatric disorders observed in patients with neurologic disease.

The American Neuropsychiatric Association: ten years of progress and a future of great promise.

The author reviews the history, accomplishments, and goals of the American Neuropsychiatric Association on the occasion of the tenth anniversary of its founding.

Safety and efficacy of ECT in patients with head injury: a case series.

Electroconvulsive therapy (ECT) is a safe and effective treatment for certain psychiatric disorders. Eleven patients who had sustained a closed head injury were treated with ECT for their psychiatric symptoms. Eight patients responded to an index course of ECT: 2 were partial responders and became responders during continuation ECT (cECT); 1 patient was a nonresponder. Post-ECT Neurobehavioral Cognitive Status Examination and Mini-Mental State Examination scores showed no significant decline (P > 0.70 and P > 0.89, respectively) from baseline. Eight patients received cECT, without any lasting cognitive side effects. These findings indicate that ECT can be used effectively in patients with a history of closed head injury, without adverse effects on cognitive functioning.

Neuropsychiatric correlates and treatment of lenticulostriatal diseases: a review of the literature and overview of research opportunities in Huntington's, Wilson's, and Fahr's diseases. A report of the ANPA Committee on Research. American Neuropsychiatric Association.

This report reviews clinical neuropsychiatric findings and opportunities for research in Huntington's, Wilson's, and Fahr's diseases. Consistent, systematic methodology is lacking among neuropsychiatric studies in these lenticulostriatal diseases. Systematic cross-sectional and longitudinal assessments are needed to ascertain the prevalence of psychiatric disorders as a function of disease course. Preliminary synthesis of existing data suggests the following heuristic relationships in these diseases: depression with parkinsonian states; personality changes with caudate or putamen disease; psychosis, impulsivity, and sexual disorders with caudate disease; dementia and mania with caudate and pallidal diseases; and compulsions with pallidal disease. Correlation of neuropsychiatric findings with disease stage, clinical signs, and radiologic, metabolic, physiologic, and pathologic markers of disease will add to our understanding of these conditions.

Changes in seizure threshold over the course of electroconvulsive therapy affect therapeutic response and are detected by ictal EEG ratings.

Therapeutic effectiveness of electroconvulsive therapy is influenced by the degree to which the stimulus intensity exceeds the seizure threshold. However, the threshold rises variably over the treatment course, confounding maintenance of desired relative stimulus intensity. In 47 depressed patients, decreases in relative stimulus intensity between treatments 1 and 6 were associated with diminished therapeutic response at treatment 6 for unilateral (UL) ECT. A multivariate model including manual ratings of ictal EEG data predicted whether seizure threshold rose with 82% accuracy. The same EEG variables were also significantly related to therapeutic response. Thus, decreases in relative stimulus intensity over the ECT course affect the therapeutic potency of UL ECT. Further, ictal EEG indices have considerable potential for predicting such stimulus intensity changes and their effect on therapeutic outcome.

The clinician-scientist in neuropsychiatry: a position statement from the Committee on Research of the American Neuropsychiatric Association.

Neuropsychiatric research seeks to improve the lives of patients with brain-based behavioral disturbances. There has been dramatic progress in diagnosis and treatment of neuropsychiatric disorders, and progress in neuroscience and biotechnology promises further success. Paradoxically, recent trends threaten to erode this progress. In this environment, neuropsychiatric clinician-scientists must advocate for the importance of research. This position statement defines neuropsychiatric research, describes current challenges to the neuropsychiatric clinician-scientist, summarizes research opportunities, describes how future neuropsychiatric clinician-investigators should be trained, and makes recommendations for promoting neuropsychiatric research.

Sex differences in brain aging: a quantitative magnetic resonance imaging study.

BACKGROUND: Little is known about the effect of sex on age-related changes in brain structure. METHODS: Quantitative magnetic resonance imaging of the brain was performed in 330 elderly (age range, 66-96 years) volunteers living independently in the community, all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images by means of computer-assisted edge detection and trace methods. High measurement reliabilities were obtained. RESULTS: Age-specific changes in brain size were significantly greater in men than women for the peripheral (sulcal) cerebrospinal fluid volume, the lateral (sylvian) fissure cerebrospinal fluid volume, and the parieto-occipital region area. Main effects of age were observed for all the remaining brain regions examined (cerebral hemisphere volume, frontal region area, temporoparietal region area, lateral ventricular volume, and third ventricle volume), but these effects were similar in men and women. Asymmetries in brain structures were not affected by aging in either sex. CONCLUSIONS: Our results are generally consistent with the few published studies on sex differences in brain aging and suggest that, for at least some structures, aging effects may be more apparent in men than women. The neurobiological bases and functional correlates of these sex differences require further investigation.

Cognitive screening instruments in neuropsychiatry: a report of the Committee on Research of the American Neuropsychiatric Association.

A 1994 survey by the Research Committee of the American Neuropsychiatric Association revealed that 58% of respondents employed formal assessment of cognitive status; the Mini-Mental State Examination (MMSE) and neuropsychological testing were the commonest techniques. Literature review on common cognitive screening instruments found that the MMSE has widespread popularity, ease of use, and a large body of research demonstrating its sensitivity to common neuropsychiatric disorders. The Committee recommends that clinicians who employ the MMSE 1) use it as a minimum screening for cognitive dysfunction; 2) employ age- and education-normative corrections; and 3) supplement it with specific measures of spatial functions, delayed memory, and executive abilities. The Modified MMSE and the Neurobehavioral Cognitive Status Examination also show promise as screening tools.

Neuropsychiatric considerations in the use of electroconvulsive therapy.

ECT is an effective and rapidly acting treatment for certain major psychiatric disorders, even in patients with neurologic illness. Further, in some cases the neurologic illness itself also responds to ECT. Patients with some types of neurologic illness may be at increased risk of neurologic or cognitive side effects from ECT, but these risks can be lowered by careful pre-ECT evaluation and optimal ECT technique.

The largest Lyapunov exponent of the EEG during ECT seizures as a measure of ECT seizure adequacy.

Attributes of the electroencephalogram (EEG) recorded during electroconvulsive therapy (ECT) seizures appear promising for decreasing the uncertainty that exists about how to define a therapeutically adequate seizure. In the present report we study whether one promising and not yet tested ictal EEG measure, the largest Lyapunov exponent (lambda1), is useful in this regard. We calculated lambda1 from 2 channel ictal EEG data recorded in 25 depressed subjects who received right unilateral ECT. We studied the relationship of lambda1 to treatment therapeutic outcome and to an indirect measure of treatment therapeutic potency, the extent to which the stimulus intensity exceeds the seizure threshold. We found lambda1 could be reliably calculated from ictal EEG data and that the global mean, maximum, and standard deviation of lambda1 were smaller in the more therapeutically potent moderately suprathreshold ECT and in therapeutic responders. These results imply a more predictable or consistent pattern of EEG seizure activity over time in more therapeutically effective ECT seizures. These findings also suggest the promise of lambda1 as a marker of ECT seizure therapeutic adequacy and build on our previous work suggesting that lambda1 may be useful for classifying seizures and for reflecting the relative physiologic impact of seizure activity.

Effect of ECT treatment number on the ictal EEG.

Recent evidence suggests that attributes of the ictal electroencephalogram (EEG) may be clinically useful for estimating the extent to which the electroconvulsive therapy (ECT) stimulus exceeds the seizure threshold (relative stimulus intensity). Such a tool could allow a practitioner, who chose, on the basis of expected therapeutic response and side effect rates, to implement stimulus dosing to maintain relative stimulus intensity over the treatment course, despite the uncertain rise in seizure threshold that occurs. One potential confounding factor is a possible systematic change in the ictal EEG over the treatment course that is not due to changes in seizure threshold. We explored the effect of treatment number by comparing ictal EEG data obtained at treatments across the ECT course that were delivered at the identical relative stimulus intensity. We found that the ictal EEG at treatment 1 was characterized by a greater mid-ictal amplitude and post-ictal suppression (trend) than subsequent treatments for barely suprathreshold unilateral ECT, but not for barely suprathreshold bilateral or moderately suprathreshold unilateral ECT, and that this change may affect therapeutic effectiveness. These findings suggest the importance of treatment-number effects for the clinical application of the ictal EEG and point to possible physiological differences between unilateral and bilateral ECT.

The relative ability of three ictal EEG frequency bands to differentiate ECT seizures on the basis of electrode placement, stimulus intensity, and therapeutic response.

Ictal EEG indices show promise for separating individual ECT seizures on the basis of treatment electrode placement (ELPL), relative stimulus intensity (Dose), and expected therapeutic response. One factor impeding the effective clinical implementation of ictal EEG indices for these purposes is uncertainty as to the relative utility of lower and higher frequency EEG activity. Recent articles are contradictory in this regard, but no data exist addressing this issue. As a result, we reanalyzed data from 44 subjects in two studies and compared the relative ability of ictal EEG data in three frequency bands to differentiate seizures as a function of ELPL, Dose, and therapeutic response. We found that the frequency band that best differentiated these groups depended on the EEG measure used, the temporal portion of the seizure, and whether ELPL, Dose, or therapeutic response was being compared.

Seizure threshold in electroconvulsive therapy (ECT) II. The anticonvulsant effect of ECT.

To measure the anticonvulsant effects of a course of electroconvulsive therapy (ECT), we used a flexible stimulus dosage titration procedure to estimate seizure threshold at the first and sixth ECT treatments in 62 patients with depression who were undergoing a course of brief pulse, constant current ECT given at moderately suprathreshold stimulus intensity. Seizure threshold increased by approximately 47% on average, but only 35 (56%) of the 62 patients showed a rise in seizure threshold. The rise in seizure threshold was associated with increasing age, but not with gender, stimulus electrode placement, or initial seizure threshold. Dynamic impedance decreased by approximately 5% from the first to the sixth ECT treatment, but there was no correlation between the change in dynamic impedance and the rise in seizure threshold. No relation was found between the rise in seizure threshold and either therapeutic response status or speed of response to the ECT treatment course. These findings confirm the anticonvulsant effect of ECT but suggest that such effects are not tightly coupled to the therapeutic efficacy of moderately suprathreshold ECT.