Jennifer J. Dunkin

Dementia caregiver burden A review of the literature and guidelines for assessment and intervention

Alzheimers disease (AD) and other dementias are common degenerative disorders in the elderly. Most AD patients are cared for at home by family members, usually elderly spouses. Although caregiving is associated with significant psychological and physical morbidity, there are wide individual differences among caregivers in how well they adapt to caregiving demands. In addition, recent data suggest that caregiver variables can be important determinants of AD patient institutionalization and that AD patients living with highly distressed caregivers may exhibit higher frequencies of behavioral problems and agitation than those living with less distressed caregivers. Predictors of caregiver outcome, predictors of institutionalization, and the effect of the caregiver on the course and symptomatology of dementia are described. A model of assessment and intervention for the physician, referral processes, and resources for the caregiver are presented.

Localized orbitofrontal and subcortical metabolic changes and predictors of response to paroxetine treatment in obsessive-compulsive disorder

Previous positron emission tomography (PET) studies of patients with obsessive-compulsive disorder (OCD) have found elevated glucose metabolic rates in the orbitofrontal cortex (OFC) and caudate nuclei that normalize with response to treatment. Furthermore, OCD symptom provocation differentially activates specific subregions of the OFC, which have distinct patterns of connectivity and serve different functions. Therefore, we sought to determine the role of specific subregions of the OFC and associated subcortical structures in mediating OCD symptoms, by determining how glucose metabolism in these structures changed with paroxetine treatment of OCD patients. We also sought to determine whether pretreatment OFC metabolism would predict response to paroxetine, as it has for other OCD treatments. Twenty subjects with OCD received [18F]-fluorodeoxyglucose (FDG)-PET scans before and after 8 to 12 weeks of treatment with paroxetine, 40 mg/day. In patients who responded to paroxetine, glucose metabolism decreased significantly in right anterolateral OFC and right caudate nucleus. Lower pretreatment metabolism in both left and right OFC predicted greater improvement in OCD severity with treatment. These results add to evidence indicating that orbitofrontal–subcortical circuit function mediates the symptomatic expression of OCD. Specific subregions of the OFC may be differentially involved in the pathophysiology of OCD and/or its response to pharmacotherapy.

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.

Neuropsychological deficits among patients with late-onset minor and major depression

Cognitive ability of minor depressed patients (N=28), major depressed patients (N=26) and healthy elderly (N=38) was examined cross-sectionally to determine if cognitive abilities of patients with late-onset depression decrease with increasing severity of disease and if cognitive scores for minor depressed patients fall between those of healthy elderly and major depressed patients. A pooled within-group principal component analysis of cognitive test scores identified five components, three of which showed significant group differences. Verbal Recall and Maintenance of Set separated controls from major depressed patients and minor from major depressed patients. Executive Functioning separated controls from minor depressed patients, and Working Memory was borderline for separating controls from major depressed patients. The component representing Nonverbal Recognition was not statistically significant. Partial correlations controlling for age and education indicate that cognitive performance does decrease as severity of depression increases, and the magnitude of the change varies from a trend to a significant deficit depending on the cognitive domain. This decline in cognitive performance parallels a similar trend observed in neuroanatomical studies in which the volume of the frontal and temporal lobes decrease with increasing severity of depression.

Reproductive events modify the effects of estrogen replacement therapy on cognition in healthy postmenopausal women

The question of whether estrogen replacement therapy (ERT) is beneficial to cognitive functioning in postmenopausal women has become controversial in the past several years. Early studies suggested that ERT improved cognitive functioning and decreased the risk of Alzheimers disease, but recent studies have failed to find any benefit. However, studies have varied in terms of the age of participants, the estrogen preparation used, whether progesterone is administered concurrently, and the study design. The present study used a randomized, placebo-controlled design and a transdermal estrogen preparation composed of 17-beta estradiol. A neuropsychological battery was administered at baseline and after completion of the 10-week trial, and test scores were grouped into four composite scores using psychometric techniques. Baseline to follow-up change was analyzed using multiple regression techniques. Results indicate that while little overall beneficial effect of estrogen was found, years since menopause was significantly related to change in executive functioning in the estrogen but not the placebo group, such that more recently postmenopausal women demonstrated greater positive change than older women. Body mass index, a gross estimate of circulating estrogen, was significantly positively related to change in attentional and psychomotor processes regardless of treatment group, and to a weaker extent, verbal memory, but only in the estrogen-treated group. These results suggest that reproductive events and levels of endogenous estrogen are related to the clinical response to ERT, but larger studies with longer follow-up periods are needed to determine the strength of these effects.

Relationships between EEG Coherence and Neuropsychological Tests in Dementia

Previous research has demonstrated differences in resting state EEG coherence among groups of subjects with dementia of the Alzheimer type (DAT), multi-infarct dementia (MID), and normal elderly controls. Since reduced coherence between brain sites has been thought to reflect functional disconnection between brain areas, we hypothesized that decreased coherence would be associated with cognitive dysfunction as assessed by neuropsychological tests. We correlated several neuropsychological tests with four coherence variables and found that reduced coherence was associated with impairment on specific neuropsychological tests in ways that conform to and supplement current knowledge about the localization of brain functions. The results are consistent with the hypothesis that coherence reflects a functional breakdown in communication between brain areas, and that coherence may be a more precise way to localize brain function than other EEG variables.

Assessment of cerebral perfusion using quantitative EEG cordance

Brain electrical activity is related to cerebral perfusion. The nature of this relationship is unclear, however, and surface-recorded activity has not been a reliable indicator of brain perfusion. We studied 27 subjects, all of whom were examined with single photon emission tomography (SPECT) and quantitative electroencephalography (QEEG), to assess associations between QEEG cordance and relative brain perfusion. Cordance has two indicator states: concordance, which may indicate high perfusion; and discordance, which may indicate low perfusion. We used multiple linear regression to assess the association between cordance and SPECT values, and found that cordance values were strongly associated with tissue perfusion. Concordance in the alpha band was associated both with mean tissue perfusion and the volume of normally perfused tissue, and it had a stronger association with perfusion than any other QEEG variable. Discordance in the beta 1 band was associated with mean perfusion, and it had a stronger association than did relative but not absolute power. These data suggest that cordance may be useful for the noninvasive assessment of brain perfusion.

Brain Metabolites and Cognitive Function among Older Depressed and Healthy Individuals Using 2D MR Spectroscopy

Brain metabolites of choline (Ch) and myo-Inisotol (mI) have been reported as elevated among geriatric depressed patients. Two-dimensional (2D) magnetic resonance spectroscopy (MRS) provides estimates of Ch, mI, and creatine (Cr) similar to one-dimensional MRS, and it also estimates the resonances of the Ch-containing compounds of phosphoethanolamine (Pe) and phosphocholine (PCh). In this cross-sectional geriatric study, 14 depressed patients and 14 healthy volunteers who were comparable in age, gender, education, comorbid medical burden, and Mini-Mental State Examination (MMSE) scores completed 2D MRS and a neurocognitive battery. A voxel in the left dorsolateral cortex, which was comprised of approximately 60% white matter, was used to estimate the CR ratios of Ch, PCh, Pe, and mI. Composite scores for cognitive function were developed for verbal learning, recall, recognition, executive function, hypothesis generation, and processing speed. Among nondepressed subjects, cognition was positively correlated with Ch/Cr and mI/Cr and negatively correlated with PCh/Cr in four domains of verbal learning, recognition, recall, and hypothesis generation. In contrast, depressed patients did not have consistent relationships between Ch/Cr, mI/Cr, and PCh/Cr and cognition. There was a significant difference in the overall pattern of associations between the four metabolites and verbal learning and processing speed in depressed patients compared to healthy controls. The attenuated relationship between metabolites and specific cognitive domains in patients with late-life MDD suggests that the level of cognitive performance observed during depressive episodes may be associated with changes in biochemistry within the frontostriatal neuronal circuitry.

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.