Susan Rosenberg-Thompson

The Neuropsychiatric Inventory Comprehensive assessment of psychopathology in dementia

We developed a new instrument, the Neuropsychiatric Inventory (NPI), to assess 10 behavioral disturbances occurring in dementia patients: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability/lability, apathy, and aberrant motor activity. The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. Both the frequency and the severity of each behavior are determined. Information for the NPI is obtained from a caregiver familiar with the patients behavior. Studies reported here demonstrate the content and concurrent validity as well as between-rater, test-retest, and internal consistency reliability; the instrument is both valid and reliable. The NPI has the advantages of evaluating a wider range of psychopathology than existing instruments, soliciting information that may distinguish among different etiologies of dementia, differentiating between severity and frequency of behavioral changes, and minimizing administration time.

Executive dysfunction predicts nonresponse to fluoxetine in major depression.

BACKGROUND Functional brain imaging studies of major depression have consistently revealed hypometabolism or hypoperfusion in specific regions of the prefrontal cortex and basal ganglia. Studies of cognitive functioning in major depression have suggested that some but not all subjects exhibit cognitive deficits that are consistent with frontal-subcortical dysfunction, although the reasons for this heterogeneity are unclear. In this study, we explored this heterogeneity among depressed subjects by examining the relationship between cognitive functioning and treatment outcome. METHOD Subjects with major depression were administered a complete neuropsychological test battery prior to treatment with fluoxetine. RESULTS There were no significant differences between responders and nonresponders to fluoxetine in terms of age, educational achievement, number of past episodes of depression, and estimated premorbid IQ. However, nonresponders performed significantly worse than responders on several pretreatment measures of executive functioning, after controlling for baseline group differences in depression severity. LIMITATIONS The results are based on a small sample of primarily female subjects, resulting in low statistical power and less generalizability to samples of male subjects with depression. CONCLUSIONS The findings suggest that subtle prefrontal dysfunction in subjects with major depression may be predictive of poor response with particular medications. Assessment of the executive functions may play a particular role in pretreatment identification of subjects likely to respond to specific medications.

Regional differences in brain electrical activity in dementia: use of spectral power and spectral ratio measures ☆

The pathologic changes in dementia of the Alzheimers type (DAT) commonly affect selected brain regions. The cortical areas affected in multi-infarct dementia (MID) are less predictable and may be secondary to subcortical gray or white matter damage that is widespread in MID. We compared several types of quantitative EEG power measures (absolute and relative power, and ratios of power) to determine their regional distribution, and their association with changes in cognitive status and age. We examined 49 subjects with clinically diagnosed mild-to-moderate DAT, 29 with mild-to-moderate MID, and 38 elderly controls (CON). We used discriminant analysis to identify, for each parameter type, the brain region and frequency band where the parameter best distinguished between groups of subjects. The parameters showed regional differences in distinguishing between DAT and MID subjects, and in their association with age and cognitive status. All parameters were useful for detecting differences between normal and demented subjects and correctly identified comparable proportions of subjects as having dementia. Subjects who were abnormal on several parameters were much more likely to have dementia. The additive effects of these parameters in correct classification suggest that they may be monitoring different physiologic processes. Combinations of several types of parameters may be more useful than individual parameters for distinguishing demented from non-demented subjects.

Neurophysiologic predictors of treatment response to fluoxetine in major depression

Treatment with antidepressants is marked by heterogeneity of response; predicting individual response to any given agent remains problematic. Neuroimaging studies suggest that response is accompanied by physiologic changes in cerebral energy utilization, but have not provided useful markers at pretreatment baseline. Using quantitative EEG (QEEG) techniques, we investigated pretreatment neurophysiologic features to identify responders and non-responders to fluoxetine. In a double-masked study, 24 adult subjects with current major depression of the unipolar type were studied over 8 weeks while receiving fluoxetine (20 mg QD) or placebo. Neurophysiology was assessed with QEEG cordance, a measure reflecting cerebral energy utilization. Response was determined with rating scales and clinical interview. Subjects were divided into discordant and concordant groups based upon the number of electrodes exhibiting discordance. The concordant group had a more robust response than the discordant group, judged by lower final Hamilton Depression (HAM-D) mean score (8.0+/-7.5 vs. 19.6+/-4.7, P = 0.01) and final Beck Depression Inventory (BDI) mean score (14.0+/-9.4 vs. 27.8+/-3.7, P = 0.015), and by faster reduction in symptoms (HAM-D: 14.0+/-5.0 vs. 23.8+/-4.1, P = 0.004 at 1 week). Groups did not differ on pretreatment clinical or historical features. Response to placebo was not predicted by this physiologic measure. We conclude that cordance distinguishes depressed adults who will respond to treatment with fluoxetine from those who will not. This measure detects a propensity to respond to fluoxetine and may indicate a more general responsiveness to antidepressants.

Altered cerebral energy utilization in late life depression

BACKGROUND Global and regional changes in cerebral energy utilization are reported to characterize late life depression. METHODS Twenty seven subjects with late life depression (9 prior to starting medication, 18 after starting) and 27 matched controls were evaluated with cordance, a quantitative EEG measure that reflects cerebral energy utilization. RESULTS Global and focal (anterior and centrotemporal) differences were present in theta-band cordance between unmedicated depressed and control subjects. Depressed subjects receiving treatment had cordance patterns similar to controls. CONCLUSIONS The presence of both diffuse and focal disturbances in energy utilization prior to initiating treatment indicates that cordance detects altered cerebral physiology in depressed patients, and that this measure may also be sensitive to treatment interventions.

Prevalence and Significance of Electroencephalographic Abnormalities in Patients with Suspected Organic Mental Syndromes

Objective: To determine the prevalence of electroencephalogram (EEG) abnormalities at different levels of cognitive impairment and to assess the possible diagnostic usefulness of the test.

Loss of High-Frequency Brain Electrical Response to Thiopental Administration in Alzheimer's-Type Dementia

Abnormal brain regions generate proportionately less high-frequency (beta) activity than nonpathological regions, a phenomenon accentuated by barbiturate administration. Using quantitative electroencephalography we examined power in the 20- to 28-Hz band in patients with dementia of the Alzheimer’s type (DAT), vascular dementia (VaD), and normal elderly controls (CON) following an IV bolus of thiopental (0.5 mg/kg). Compared to both CON and VaD subjects, DAT subjects showed a marked loss of beta power elicited across the cortex, with largest differences noted in the frontal region. Losses were most significant for the peak response recorded at 30 to 90 s postinjection and persisted during the 5-minute follow-up period. We hypothesize that differences in this electrocerebral response reflect differences in the underlying neuropathology of DAT and VaD subjects. A thiopental challenge may be well suited for the in vivo assessment of brain function in dementias characterized by prominent cortical pathology.

Quantitative EEG Correlates of Outcome in Older Psychiatric Patients: Part II: Two-Year Follow-Up of Patients With Depression

The authors examined quantitative electroencephalographc (QEEG) coherence in 37 depressed elderly patients and performed 2-year follow-up evaluations. All subjects had equivocal cognitive impairment, but none had delirium or dementia. More than 40% (16/37) recovered from depression, and 38% (14/37) remained well for 2 years. Twenty-four percent (n = 9) had died within 2 years, most from cardiac causes. Low trans-Rolandic coherence from the left hemisphere was strongly associated with mortality: 44% (7/16) of those with low coherence died, and 78% (7/9) of those who died had low coherence. Among survivors (n = 28) at follow-up, low coherence was significantly associated with lower functional status. These findings suggest that the coherence variable measures actual neurophysiology differences between groups of depressed patients and these differences are associated with the heterogeneous outcomes of depression in elderly patients.

Quantitative EEG correlates of outcome in older psychiatric patients: Part I: Cross-sectional and longitudinal assessment of patients with dementia

Using quantitative electroencephalographic coherence (a measure of synchronized electrical activity between brain regions) the authors examined heterogeneity in clinical presentation and outcome inpatients with dementia. Patients (N = 114) with mild-to-moderate dementia of the Alzheimers type (DAT) or multi-infarct dementia (MID) were examined for coherence from the left hemisphere. More than 70% diagnostic accuracy in distinguishing between DAT and MID subjects was achieved using coherence measures alone. Also, decreased coherence measured across the Rolandic fissure in the left hemisphere was significantly associated with poorer functional status of subjects at 2-year follow-up, despite similar levels of cognitive impairment at baseline. These findings suggest that coherence is a useful measure for assessment and for prediction of the course of illness inpatients with dementia.