The Effect of Memory Training on Memory Control Beliefs in Older Adults with Subjective Memory Complaints.

Objective: To study whether memory control beliefs predict response to memory training, or change as a result of participating in memory training. Methods: Eighty community based participants with subjective memory complaints Community-based study at UCLA were randomized to one of three conditions: Memory Training, the program consisted of weekly 120-minute classes featuring instruction in three specific strategies: Method of Loci; Chunking Technique; and Face-Name Association, Health Education or Wait-List over seven weeks. All participants underwent pre- and 1-week post-intervention follow-up memory testing for recalling word lists (in serial order and any order) and face-name pairs. Memory control beliefs were assessed at baseline and follow-up using the Memory Controllability Inventory, which consists of four subscales; Present Ability; Potential Improvement; Effort Utility; and Inevitable Decrement. Results: Sixty-three participants (mean age [SD] 68.3 [6.7] years) were included in the analysis. ANCOVA revealed significant group differences in the Present Ability subscale, F2,58 = 4.93, p =.01. Participants in the Memory Training group significantly improved on the Present Ability subscale compared to the Health Education group (mean difference =.96, SE =.31, p =.003, effect size = 0.93). From regression analyses, baseline Memory Controllability Inventory subscales did not significantly predict memory performance after memory training. Conclusions: Baseline memory control beliefs did not predict memory performance following the intervention, but participating in memory training enhanced memory control beliefs about current memory function. These results suggest that participating in memory training can enhance confidence in one's memory ability.

Estrogen and response to sertraline in postmenopausal women with major depressive disorder: a pilot study.

OBJECTIVE: Pilot study examining the effects of estrogen therapy (ET) on antidepressant response in postmenopausal women with major depressive disorder (MDD). METHODS: Twenty-two subjects received sertraline at 50mg/day for one week, with an increase to 100mg/day at week 2 for a 10-week trial. Transdermal estrogen or placebo patches 0.1mg were randomly administered concurrent with the initiation of sertraline treatment. The 21 item Hamilton Depression Rating Scale (HDRS-21) was administered to all patients at baseline and weekly thereafter. RESULTS: Both groups showed a similar significant reduction in HDRS-21 scores by the end of the study. There was no significant difference between the two treatment groups at the end of the 10-week trial, but the women receiving sertraline with ET showed significantly greater early improvement (weeks 2-4) compared to the women receiving sertraline with placebo. CONCLUSIONS: Sertraline is an effective antidepressant for postmenopausal women with MDD. ET does not alter the response rate to antidepressant therapy however ET may play a role in accelerating the antidepressant response.

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 Alzheimer's 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.

Cognitive and physiologic correlates of subclinical structural brain disease in elderly healthy control subjects.

CONTEXT: Healthy elderly persons commonly show 4 types of change in brain structure-cortical atrophy, central atrophy, deep white-matter hyperintensities, and periventricular hyperintensities-as forms of subclinical structural brain disease (SSBD). OBJECTIVES: To characterize the volumes of SSBD present with aging and to determine the associations of SSBD, physiology, and cognitive function. DESIGN: Cross-sectional study. SETTING: University of California, Los Angeles, Neuropsychiatric Institute. SUBJECTS: Forty-three community-dwelling healthy control subjects, aged 60 through 93 years. MAIN OUTCOME MEASURES: Volumetric magnetic resonance imaging, neuropsychological testing, and quantitative electroencephalographic coherence (functional connectivity) between brain regions. RESULTS: Regression models demonstrated significant relationships between SSBD volumes, age, cognitive performance, and connectivity. Cortical and central atrophy and periventricular hyperintensities had significant associations with age while deep white-matter hyperintensities did not. Posterior atrophy showed stronger associations with age than did anterior atrophy. Only a subset of subjects at older ages showed large SSBD volumes; older subjects primarily showed increasing variance of SSBD. Although all subjects scored within the normal range on cognitive testing, SSBD volume was inversely related to performance, most notably on the Trail-Making Test part B and the Shipley-Hartford Abstract Reasoning test. Coherence had significant associations with SSBD. Path analysis supported mediation of the effects of deep white-matter hyperintensities and periventricular hyperintensities on cognition by altered connectivity. For several measures, cognitive performance was best explained by coherence, and only secondarily by SSBD. CONCLUSIONS: Modest volumes of SSBD were associated with decrements in cognitive performance within the normal range in healthy subjects. Lower coherence was associated with greater volumes of SSBD and increasing age. Path analysis models suggest that brain functional connectivity mediates some effects of SSBD on cognition.

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.

Estrogen replacement therapy in the treatment of major depressive disorder in perimenopausal women.

BACKGROUND: Increased vulnerability to mood disorders has been reported during perimenopause. Fluctuating estrogen levels accompany the perimenopausal transition. Thus, estrogen replacement therapy (ERT) has been proposed as a potentially effective treatment for mood disorders occurring during perimenopause. METHOD: We examined the efficacy of ERT in the treatment of depression in 16 perimenopausal women with DSM-IV-defined major depressive disorder who were participating in the Mood Disorders Research Program at the Department of Psychiatry of the University of California, Los Angeles. Ten antidepressant- and ERT-naive women received ERT alone. Six women who were nonresponders or partial responders to an antidepressant received ERT in addition to existing treatment with fluoxetine. The Hamilton Rating Scale for Depression (HAM-D) was administered to all patients at baseline and weekly thereafter during the 8-week open-protocol trial. Partial response was operationalized as a final HAM-D score < or = 50% of the baseline score. Remission was defined as a final HAM-D score < or = 7. RESULTS: All patients exhibited clinical improvement as measured by HAM-D scores after the first week of treatment. Of the 10 perimenopausal depressed women receiving ERT alone, 6 remitted, 3 partially responded to treatment, and 1 did not respond by the end of the trial. Of the 6 women receiving antidepressant treatment with ERT, 1 patient remitted and 5 had a partial response by the end of the trial. CONCLUSION: This small study suggests that for some antidepressant-naive perimenopausal women with clinical depression, ERT may have antidepressant efficacy. In depressed women who have minimal response to a selective serotonin reuptake inhibitor, ERT may augment response. Further controlled trials are needed.

Pretreatment neurophysiological and clinical characteristics of placebo responders in treatment trials for major depression.

RATIONALE: High placebo response rates are a confound in treatment trials for major depressive disorder (MDD). A method for prospective identification of placebo responders could enhance the efficiency of clinical trials. OBJECTIVE: The objective was to identify the neurophysiological, symptomatic, and cognitive characteristics of subjects who were likely to respond to placebo in clinical trials for MDD. METHODS: Fifty-one subjects with MDD were treated in clinical trials with either fluoxetine ( n=24) or venlafaxine ( n=27) versus placebo. All subjects underwent pretreatment assessment with quantitative electroencephalographic (QEEG) power and cordance, as well as symptom ratings and neuropsychological testing. After a 1-week single-blind placebo lead-in, subjects were randomized to double-blind placebo controlled treatment with a medication or placebo. At the end of 8 weeks, the blind was broken and treatment response assessed. Response was defined by a final Hamilton Depression Rating Scale score of

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 Alzheimer's 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.

MMSE items predict cognitive decline in persons with genetic risk for Alzheimer's disease.

Performance on individual Mini-Mental State Examination (MMSE) items can predict incident Alzheimer's disease (AD). The purpose of the current study is to determine whether, in nondemented persons with and without the apolipoprotein E-4 (APOE-4) genetic risk for AD, a subset of MMSE items predict cognitive decline. Fifty-four nondemented subjects, 23 with at least one copy of the APOE-4 allele and 31 without APOE-4, were given the MMSE and cognitive tests at baseline and 2-year follow-up. MMSE total score and a subset of MMSE items including delayed recall, serial 7s, pentagon, and orientation to time and place were used to predict change on cognitive tests. The subset of MMSE items significantly predicted decline in visuo-spatial construction and naming in APOE-4 carriers but not in noncarriers. Performance on a subset of MMSE items, combined with APOE-4 genotype, may aid in identifying high-risk persons for research or follow-up.

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.

Estrogen replacement therapy is associated with less progression of subclinical structural brain disease in normal elderly women: a pilot study.

BACKGROUND: Cortical atrophy, central atrophy, deep white-matter hyperintensities, and periventricular hyperintensities are reported in normal aging. OBJECTIVES: We examined the effects of estrogen replacement therapy (ERT) on these forms of 'subclinical structural brain disease' (SSBD) in normal, postmenopausal women in a pilot, naturalistic, longitudinal study of 15 subjects. METHODS: Two assessments were performed at least two years apart, with volumetric magnetic resonance imaging (MRI) and neuropsychological testing. RESULTS: Women receiving open-label ERT showed significantly less progression of SSBD than those who did not. CONCLUSIONS: The association between reduced SSBD progression and ERT suggests this intervention could help preserve normal brain structure in healthy elderly women.

Longitudinal progression of subclinical structural brain disease in normal aging.

OBJECTIVE: The authors describe four types of brain structural change in "normal aging:" cortical atrophy, central atrophy, deep white-matter hyperintensities (DWMH), and periventricular hyperintensities (PVH). Cross-sectional investigations have reported that greater volumes of these forms of "subclinical structural brain disease" (SSBD) were found with increasing age. Greater volumes were also associated with poorer cognition, even though subjects performed within the normal range. The natural history of these forms of SSBD and their functional impact are not well established. METHODS: Twenty-nine normal subjects, ages 60-89, were examined longitudinally by volumetric magnetic resonance imagery, with two assessments performed at least 2 years apart; 26 also completed neuropsychological testing to evaluate processing speed, executive functions, language, and other cognitive functions. Associations between structure and function were evaluated with regression models. RESULTS: For most subjects, the volumes for signs of all types of SSBD were found to have increased; for many subjects, increases were small, and a few showed no change or small decreases. PVH and DWMH increases were predicted by baseline cerebrovascular risk factors. Cognitive test performance changed little over time for these normal subjects. CONCLUSIONS: SSBD volumes increased for most subjects over time, with small average increases for most types. Pretreatment cerebrovascular risk factors were associated with greater increases of PVH and DWMH, suggesting that progression of these types of SSBD may be amenable to intervention.