Perceived social support declines after deep brain stimulation surgery in patients with Parkinson's disease.

INTRODUCTION: The Social Provisions Scale (SPS) measures a person's perceived social support. We evaluated the perceived social support in Parkinson's disease (PD) patients before and after subthalamic nucleus (STN) deep brain stimulation (DBS) and its impact on clinical outcomes following DBS. METHODS: We analyzed 55 PD patients who underwent STN DBS surgery and completed the SPS, PDQ-39, and MDS-UPDRS Parts I-IV before and 6-12 months after surgery. Some patients also completed global cognitive, mood and apathy scales. Caregivers completed the CBI at each visit. Linear regression models and linear mixed models evaluated the association between the SPS baseline score, MDS-UPDRS and PDQ-39 scores, the association between MDS-UPDRS, CBI and the SPS follow-up score, and the association between SPS, global cognition and other psychological variables. RESULTS: DBS implantation improved MDS-UPDRS I-IV and PDQ-39 scores. Perceived social support declined after DBS (baseline SPS total 82.55 ± 7.52 vs. follow-up SPS total 78.83 ± 9.02, p = 0.0001). Baseline SPS total score was not significantly associated with the MDS-UPDRS or PDQ-39 scores at follow-up. MDS-UPDRS scores and the CBI at follow-up had no significant association with SPS total score at follow-up. Measures of global cognition, mood and apathy were associated with the SPS before and after DBS, and the association was independent of STN DBS. CONCLUSION: After STN DBS, PD patients experienced a decrease in perceived social support, but baseline perceived social support did not impact clinical outcomes. It is important to further identify factors that may contribute to this perception of worsened social support.

Decline of verbal fluency with lateral superior frontal gyrus penetration in subthalamic nucleus deep brain stimulation for Parkinson disease.

OBJECTIVE: Verbal fluency (VF) decline is a well-recognized adverse cognitive outcome following subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinson disease (PD). The mechanisms underlying VF decline, whether from stimulation, lesioning, or both, remain unclear. This study aims to investigate the unique effects of DBS lead trajectory on VF beyond previously reported effects of active contact location. METHODS: The study population included 56 patients with idiopathic PD who underwent bilateral STN DBS. Phonemic and semantic VF scores were compared pre- and postoperatively. Features of the electrode trajectory were measured on postoperative imaging, including distance from the falx cerebri, distance from the superior frontal sulcus, and caudate nucleus penetration. The authors used t-tests, Pearson's correlation, and multiple linear regression analyses to examine the relationship between VF change and demographic, disease, and electrode trajectory variables. RESULTS: The laterality of entry within the left superior frontal gyrus (SFG) predicted greater phonemic VF decline (sr2 = 0.28, p < 0.001) after controlling for active contact location. VF change did not differ by the presence of caudate nucleus penetration in either hemisphere (p > 0.05). CONCLUSIONS: Lateral penetration of the SFG in the left hemisphere is associated with worsening phonemic VF and has greater explanatory power than active contact location. This may be explained by lesioning of the lateral SFG-Broca area pathway, which is implicated in language function.

The impact of dispositional optimism and depression on post-operative motor functioning following deep brain stimulation surgery for Parkinson's disease.

INTRODUCTION: The primary goal of subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) is to improve motor function. Dispositional optimism has been associated with better physical outcomes following a rehabilitation program in PD but has not been investigated in relation to STN-DBS. This study investigated the influence of dispositional optimism on motor outcomes following STN-DBS in individuals with PD. METHODS: A retrospective data analysis of 33 individuals with PD who underwent STN-DBS was conducted. Linear regression was used to determine whether dispositional optimism, measured by the Life Orientation Test-Revised questionnaire, predicted change in motor symptoms following DBS surgery, as assessed by the Movement Disorder Society-sponsored revision of the Unified PD Rating Scale, Part III. Self-reported levels of depressive and anxiety symptoms were included as co-variates. RESULTS: Higher pre-operative dispositional optimism combined with less self-reported depressive symptoms predicted greater post-operative improvement in motor symptoms from the baseline OFF-medication to post-operative ON-medication/ON-stimulation state, accounting for 38.8% of the variance in post-operative change. CONCLUSION: The large percentage of variance in post-STN-DBS motor change predicted by pre-operative dispositional optimism and depressive symptoms suggests that assessment of these variables prior to surgery may provide valuable information for clinicians regarding the surgery's ultimate initial motor benefit for individuals with PD. If modifiable, these variables may provide cost-effective targets to improve motor outcomes of STN-DBS in PD.

Localization of motor and verbal fluency effects in subthalamic DBS for Parkinson's disease.

INTRODUCTION: Subthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson's disease (PD) but can worsen verbal fluency (VF). An optimal site of stimulation for overall motor improvement has been previously identified using an atlas-independent, fully individualized, field-modeling approach. This study examines if cardinal motor components (bradykinesia, tremor, and rigidity) share this identified optimal improvement site and if there is co-localization with a site that worsens VF. METHODS: An atlas-independent, field-modeling approach was used to identify sites of maximal STN DBS effect on overall and cardinal motor symptoms and VF in 60 patients. Anatomic coordinates were referenced to the STN midpoint. Symptom severity was assessed with the MDS-UPDRS part III and established VF scales. RESULTS: Sites for improved bradykinesia and rigidity co-localized with each other and the overall part III site (0.09 mm lateral, 0.93 mm posterior, 1.75 mm dorsal). The optimal site for tremor was posterior to this site (0.10 mm lateral, 1.40 mm posterior, 1.93 mm dorsal). Semantic and phonemic VF sites were indistinguishable and co-localized medial to the motor sites (0.32 mm medial, 1.18 mm posterior, 1.74 mm dorsal). CONCLUSION: This study identifies statistically distinct, maximally effective stimulation sites for tremor improvement, VF worsening, and overall and other cardinal motor improvements in STN DBS. Current electrode sizes and voltage settings stimulate all of these sites simultaneously. However, future targeted lead placement and focused directional stimulation may avoid VF worsening while maintaining motor improvements in STN DBS.

Executive function and gait in older adults with cognitive impairment.

BACKGROUND: Cognitive impairment has been shown to predict falls risk in older adults. The ability to step accurately is necessary to safely traverse challenging terrain conditions such as uneven or slippery surfaces. However, it is unclear how well persons with cognitive impairment can step accurately to avoid such hazards and what specific aspects of cognition predict stepping ability in different patient populations. METHODS: Healthy older adults (NC), patients with Mild Cognitive Impairment with only memory impairment (MCI-EF) or memory and executive function impairments (MCI+EF) and early Alzheimer's patients (AD) were timed as they performed a stepping accuracy test with increasing cognitive demand (Walking Trail-Making Test; W-TMT), which required stepping on instrumented targets with either increasing sequential numbers (W-TMT A) or alternating sequential numbers and letters (W-TMT B). RESULTS: After accounting for age and baseline walking speed, the AD and MCI+EF groups were significantly slower than the NC and MCI-EF groups on the task with the highest cognitive demand, W-TMT B (interaction effect F = 6.781, p <.0001). No group differences were noted on the W-TMT A task that was less cognitively demanding. Neuropsychological measures of executive functioning were associated with slower W-TMT B performance, whereas memory, visual attention and visual spatial skills were not (adjusted R(2) = 0.42). CONCLUSIONS: Executive function is important for stepping performance, particularly under more complex environmental conditions.

Postmenopausal hormone treatment alters neural pathways but does not improve verbal cognitive function.

OBJECTIVE: Cognitive outcomes in trials of postmenopausal hormone treatment have been inconsistent. Differing outcomes may be attributed to hormone formulation, treatment duration and timing, and differential cognitive domain effects. We previously demonstrated treatment benefits on visual cognitive function. In the present study, we describe the effects of hormone treatment on verbal outcomes in the same women, seeking to understand the effects of prior versus current hormone treatment on verbal function. METHODS: This is a cross-sectional evaluation of 57 women (38 hormone users [25 prior long-term users and 13 current users] and 19 never-users). Hormone users took identical formulations of estrogen or estrogen + progestin (0.625 mg/d conjugated equine estrogens with or without medroxyprogesterone acetate) for at least 10 years, beginning within 2 years of menopause. Women were evaluated with tests of verbal function and functional magnetic resonance imaging (fMRI) of a verbal discrimination task. RESULTS: All women scored similarly on assessments of verbal function (Hopkins Verbal Learning Test and a verbal discrimination task performed during the fMRI scanning session); however, women ever treated with hormones had more left inferior frontal (T = 3.72; P < 0.001) and right prefrontal cortex (T = 3.53; P < 0.001) activation during the verbal task. Hormone-treated women performed slightly worse on the verbal discrimination task (mean accuracy 81.72 ±â€Š11.57 ever-treated, 85.30 ±â€Š5.87 never-treated, P = 0.14), took longer to respond (mean reaction time 1.10 ±â€Š0.17 s ever-treated, 1.02 ±â€Š0.11 never-treated, P = 0.03), and remembered fewer previously viewed words (mean accuracy 62.21 ±â€Š8.73 ever-treated, 65.45 ±â€Š7.49 never-treated, P = 0.18). Increased posterior cingulate activity was associated with longer response times (R = 0.323, P = 0.015) and worse delayed verbal recall (R = -0.328, P = 0.048), suggesting that increased activation was associated with less efficient cognitive processing. We did not detect between group differences in activation in the left prefrontal cortex, superior frontal cortex, thalamus, or occipital/parietal junction. CONCLUSIONS: Although current and past hormone treatment was associated with differences in neural pathways used during verbal discrimination, verbal function was not higher than never-users.

Impact of combined estradiol and norethindrone therapy on visuospatial working memory assessed by functional magnetic resonance imaging.

CONTEXT: Hormones regulate neuronal function in brain regions critical to cognition; however, the cognitive effects of postmenopausal hormone therapy are controversial. OBJECTIVE: The goal was to evaluate the effect of postmenopausal hormone therapy on neural circuitry involved in spatial working memory. DESIGN: A randomized, double-blind, placebo-controlled crossover study was performed. SETTING: The study was performed in a tertiary care university medical center. PARTICIPANTS: Ten healthy postmenopausal women of average age 56.9 yr were recruited. INTERVENTIONS: Volunteers were randomized to the order they received hormone therapy (5 microg ethinyl estradiol and 1 mg norethindrone acetate). Subjects received hormone therapy or placebo for 4 wk, followed by a 1-month washout period with no medications, and then received the other treatment for 4 wk. At the end of each 4-wk treatment period, a functional magnetic resonance imaging study was performed using a nonverbal (spatial) working memory task, the Visual Delayed Matching to Sample task. MAIN OUTCOME MEASURE: The effects of hormone therapy on brain activation patterns were compared with placebo. RESULTS: Compared with the placebo condition, hormone therapy was associated with a more pronounced activation in the prefrontal cortex (BA 44 and 45), bilaterally (P < 0.001). CONCLUSIONS: Hormone therapy was associated with more effective activation of a brain region critical in primary visual working memory tasks. The data suggest a functional plasticity of memory systems in older women that can be altered by hormones.

Distinct cognitive effects of estrogen and progesterone in menopausal women.

The effects of postmenopausal hormone treatment on cognitive outcomes are inconsistent in the literature. Emerging evidence suggests that cognitive effects are influenced by specific hormone formulations, and that progesterone is more likely to be associated with positive outcomes than synthetic progestin. There are very few studies of unopposed progesterone in postmenopausal women, and none that use functional neuroimaging, a sensitive measure of neurobiological function. In this study of 29 recently postmenopausal women, we used functional MRI and neuropsychological measures to separately assess the effects of estrogen or progesterone treatment on visual and verbal cognitive function. Women were randomized to receive 90 days of either estradiol or progesterone counterbalanced with placebo. After each treatment arm, women were given a battery of verbal and visual cognitive function and working memory tests, and underwent functional MRI including verbal processing and visual working memory tasks. We found that both estradiol and progesterone were associated with changes in activation patterns during verbal processing. Compared to placebo, women receiving estradiol treatment had greater activation in the left prefrontal cortex, a region associated with verbal processing and encoding. Progesterone was associated with changes in regional brain activation patterns during a visual memory task, with greater activation in the left prefrontal cortex and right hippocampus compared to placebo. Both treatments were associated with a statistically non-significant increase in number of words remembered following the verbal task performed during the fMRI scanning session, while only progesterone was associated with improved neuropsychological measures of verbal working memory compared to placebo. These results point to potential cognitive benefits of both estrogen and progesterone.

Inhibitory changes after age 60 and their relationship to measures of attention and memory.

This study examined the relationship between age and inhibitory functioning within a sample of older adults ranging in age from 60 to 85 years old. On the basis of earlier research, and confirmed by factor analysis, measures typically referred to as frontal lobe tasks were used as measures of inhibitory functioning. Findings demonstrated that inhibitory processes continued to decline with advancing age within the older sample. In addition, the role of inhibition in age-related performance deficits on a verbal list learning measure and an attention measure was examined. Hierarchical regression analyses showed that inhibition accounted for a significant proportion of the age-related variance on the two cognitive measures, whereas measures of reading speed accounted for a smaller proportion of the variance. In addition, when inhibition was first covaried out, reading speed no longer accounted for a significant proportion of the age-related variance. It is argued that inhibition is an important contributor to age-related performance decrements in cognition.

Functional neuroimaging of emotional processing in women with polycystic ovary syndrome: a case-control pilot study.

OBJECTIVE: To evaluate emotional processing in women with insulin-resistant polycystic ovary syndrome (IR-PCOS) and its relationship to glucose regulation and the mu-opioid system. DESIGN: Case-control pilot. SETTING: Tertiary referring medical center. PATIENT(S): Seven women with IR-PCOS and five non-insulin-resistant controls, aged 21-40 years, recruited from the general population. INTERVENTION(S): Sixteen weeks of metformin (1,500 mg/day) in women with IR-PCOS. MAIN OUTCOME MEASURE(S): Assessment of mood, metabolic function, and neuronal activation during an emotional task using functional magnetic resonance imaging (fMRI), and mu-opioid receptor availability using positive emission tomography (PET). RESULT(S): We found that insulin-resistant PCOS patients [1] had greater limbic activation during an emotion task than controls (n = 5); [2] trended toward decreased positive affect and increased trait anxiety; [3] after metformin treatment, had limbic activation that no longer differed from controls; and [4] had positive correlations between fMRI limbic activation during emotional processing and mu-opioid binding potential. CONCLUSION(S): Patients with IR-PCOS had greater regional activation during an emotion task than the controls, although this resolved with metformin therapy. Alterations in mu-opioid neurotransmission may underlie limbic system activity and mood disorders in IR-PCOS.

Change in fatigue after bilateral subthalamic nucleus deep brain stimulation for Parkinson's disease.

BACKGROUND: Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) improves motor function in patients with medically intractable Parkinson's disease (PD), but the effects of STN DBS on fatigue are unknown. The purpose of this study was to examine the effects of STN DBS on fatigue scores in patients with PD. METHODS: Twenty PD patients underwent bilateral STN DBS surgery at our institution from 2007 to 2009. Only data from the 17 patients who completed the Parkinson Fatigue Scale (PFS) and Unified PD Rating Scale (UPDRS) before and approximately 6 months after surgery were analyzed. Other evaluations included the Geriatric Depression Scale (GDS), Apathy Evaluation Scale (AES), and Epworth Sleepiness Scale (ESS). RESULTS: When the cohort was analyzed as a whole, there was no significant change in the mean or binary PFS score from baseline to the 6 month evaluation. However, the fatigue response of individual subjects was variable. Six of 12 subjects with fatigue before surgery were not fatigued post-operatively, while 3/5 subjects without fatigue before surgery became fatigued after DBS surgery. Fatigue in 8 subjects remained unchanged. Change in fatigue scores correlated significantly with change in the motor UPDRS, GDS and AES. Improvement in PFS also correlated with a higher PFS baseline score and higher baseline UPDRS motor off score. CONCLUSIONS: Changes in fatigue severity were not observed in our cohort as a whole, but there were changes in fatigue on an individual level. These changes appear to be related to the effects of STN DBS on motor improvement and mood.

Hormonal environment affects cognition independent of age during the menopause transition.

CONTEXT: Cognitive decline is prevalent in aging populations, and cognitive complaints are common during menopause. However, the extent of hormonal influence is unclear, particularly when considered independent of the aging process. OBJECTIVE: We sought to determine differences in cognitive function attributable to menopause, hypothesizing that differences would be associated with reproductive rather than chronological age. DESIGN AND SETTING: In this cross-sectional study at a university hospital, we combined neuropsychological measures with functional magnetic resonance imaging to comprehensively assess cognitive function. PARTICIPANTS: Sixty-seven menopausal women, aged 42-61 yr, recruited from a population-based menopause study, grouped into menopause stages based on hormonal and cycle criteria (premenopause, perimenopause, and postmenopause), participated in the study. MAIN OUTCOME MEASURES: Neuropsychological and functional magnetic resonance imaging measures of verbal, visual, and executive cognitive function. RESULTS: We found age-independent menopause effects on verbal function. Menopause groups differed in phonemic verbal fluency (F = 3.58, P < 0.019) and regional brain activation (inferior frontal cortex: corrected P < 0.000 right, P < 0.036 left; left prefrontal cortex: P < 0.012); left temporal pole: P < 0.001). Verbal measures correlated with estradiol and FSH (phonemic fluency: R = 0.249, P < 0.047 estradiol, R = -0.275, P < 0.029 FSH; semantic fluency: R = 0.318, P < 0.011 estradiol, R = -0.321, P < 0.010 FSH; right inferior frontal cortex: R = 0.364, P < 0.008 FSH; left inferior frontal cortex: R = -0.431, P < 0.001 estradiol, left prefrontal cortex: R = 0.279, P < 0.045 FSH; left temporal pole: R = -0.310, P < 0.024 estradiol, R = 0.451, P < 0.001 FSH; left parahippocampal gyrus: R = -0.278, P < 0.044 estradiol; left parietal cortex: R = -0.326, P < 0.017 estradiol). CONCLUSIONS: Results suggest that verbal fluency mechanisms are vulnerable during the menopausal transition. Targeted intervention may preserve function of this critical cognitive domain.

Postmenopausal hormone use impact on emotion processing circuitry.

Despite considerable evidence for potential effects of estrogen on emotional processing, several studies of postmenopausal women who began hormone therapy (HT) remote from menopause report no effects of HT on emotional measures. As early HT initiation may preserve brain mechanisms, we examined effects of HT on emotional processing in postmenopausal women who started HT early after menopause. We performed a cross-sectional comparison of 52 postmenopausal women 66±5 years old, including 15 users of conjugated equine estrogen, 20 users of conjugated equine estrogen plus medroxyprogesterone acetate, and 17 who never used hormones (NT). All hormone users started therapy within two years of menopause, and received at least 10 years of continuous therapy. Outcomes were fMRI-detected brain activity and behavioral measures during an emotional processing picture rating task. During processing of positive pictures, NT women had greater activation than estrogen treated women in medial prefrontal cortex extending to the anterior cingulate, and more activation than estrogen plus progestin treated women in the insula. During processing of negative pictures, estrogen treated women had higher activation than NT women in the entorhinal cortex. Current compared to past HT users showed greater activation in the hippocampus and higher emotion recognition accuracy of neutral stimuli. Estrogen plus progestin treated women had slower response time than NT women when rating all pictures. In conclusion, hormone use was associated with differences in brain functional responses during emotional processing. These fMRI effects were more prominent than those observed for behavioral measures and involved brain regions implicated in cognitive-emotional integration.

The right to move: a multidisciplinary lifespan conceptual framework.

This paper addresses the health problems and opportunities that society will face in 2030. We propose a proactive model to combat the trend towards declining levels of physical activity and increasing obesity. The model emphasizes the need to increase physical activity among individuals of all ages. We focus on the right to move and the benefits of physical activity. The paper introduces a seven-level model that includes cells, creature (individual), clan (family), community, corporation, country, and culture. At each level the model delineates how increased or decreased physical activity influences health and well-being across the life span. It emphasizes the importance of combining multiple disciplines and corporate partners to produce a multifaceted cost-effective program that increases physical activity at all levels. The goal of this paper is to recognize exercise as a powerful, low-cost solution with positive benefits to cognitive, emotional, and physical health. Further, the model proposes that people of all ages should incorporate the "right to move" into their life style, thereby maximizing the potential to maintain health and well-being in a cost-effective, optimally influential manner.

Insulin resistance influences central opioid activity in polycystic ovary syndrome.

This pilot study describes a relationship between insulin resistance and µ-opioid neurotransmission in limbic appetite and mood-regulating regions in women with polycystic ovary syndrome (PCOS), suggesting that insulin-opioid interactions may contribute to behavioral and reproductive pathologies of PCOS. We found that [1] patients with PCOS who are insulin-resistant (n = 7) had greater limbic µ-opioid receptor availability (nondisplaceable binding potential) than controls (n = 5); [2] receptor availability was correlated with severity of insulin resistance; and [3] receptor availability normalized after insulin-regulating treatment.

Early initiation of hormone therapy in menopausal women is associated with increased hippocampal and posterior cingulate cholinergic activity.

CONTEXT: The role of ovarian hormones in maintaining neuronal integrity and cognitive function is still debated. This study was undertaken to clarify the potential relationship between postmenopausal hormone use and the cholinergic system. OBJECTIVE: We hypothesized that early initiated hormone therapy (HT) preserves the cholinergic system and that estrogen therapy (ET) would be associated with higher levels of acetylcholinesterase activity in the posterior cingulate cortex and hippocampus compared to estrogen plus progestin therapy (EPT) or no HT. DESIGN AND SETTING: We conducted a cross-sectional study at a university teaching hospital. PATIENTS: Fifty postmenopausal women (age, 65.2 ± 0.7 yr) with early long-term HT (n = 34; 13 ET and 21 EPT) or no HT (n = 16) participated in the study. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURE: We measured cholinergic activity (acetylcholinesterase) in the hippocampus and posterior cingulate brain regions as measured by N-[(11)C]methylpiperidin-4-yl propionate and positron emission tomography as a marker of cholinergic function. RESULTS: Significant effects of treatment on cholinergic activity measures were obtained in the left hippocampus (F = 3.56; P = 0.04), right hippocampus (F = 3.42; P = 0.04), and posterior cingulate (F = 3.76; P = 0.03). No significant effects were observed in a cortical control region. Post hoc testing identified greater cholinergic activity in the EPT group compared to the no-HT group in the left hippocampus (P = 0.048) and posterior cingulate (P = 0.045), with a nonstatistically significant trend in the right hippocampus (P = 0.073). CONCLUSIONS: A differential effect of postmenopausal ET and EPT on cholinergic neuronal integrity was identified in postmenopausal women. The findings are consistent with a preservation of cholinergic neuronal integrity in the EPT group.

Short-term hormone treatment modulates emotion response circuitry in postmenopausal women.

OBJECTIVE: To study the effects of combination hormone therapy (HT) on emotional processing in postmenopausal women with use of functional neuroimaging. DESIGN: A randomized, double-blind, placebo-controlled crossover study was performed. SETTING: A tertiary care university medical center. PARTICIPANT(S): Ten healthy postmenopausal women (mean age 56.9 years, SD = 1.4 years) were recruited. INTERVENTION(S): Women were assigned randomly to the order they received combined HT, 5 microg ethinyl E(2) and 1 mg norethindrone acetate, and placebo. Volunteers received HT or placebo for 4 weeks, followed by a 1-month washout period, and then received the other treatment for 4 weeks. Subjects participated in a functional magnetic resonance imaging emotional processing task, where they were asked to rate emotional pictures as positive, negative, or neutral. MAIN OUTCOME MEASURE(S): Brain activation patterns were compared between HT and placebo conditions within subjects. RESULT(S): During negative emotional presentations, after subtracting the effect of neutral images, areas of significant differences between HT and placebo conditions were identified in the orbital, frontal, cingulate, and occipital cortices. During positive emotional image presentation there were significant differences between placebo and HT conditions within the medial frontal cortex. CONCLUSIONS: Short-term menopausal treatment with combination HT affects regional brain activity within areas implicated in emotional processing.

Early menopausal hormone use influences brain regions used for visual working memory.

OBJECTIVE: The cognitive benefit of postmenopausal hormone use is controversial; however, timing of treatment close to menopause may increase the likelihood of preserving cognitive function. We examined the effects of early-initiation hormone use on visual working memory, hypothesizing that long-term hormone use is associated with greater brain activation during visual working memory. METHODS: This was a cross-sectional comparison of long-term early hormone users-current (n = 13) and past (n = 24; 2.1 +/- 1.0 years off hormones)-with never users (n = 18), using a visual memory task and functional magnetic resonance imaging (MRI). We evaluated 55 women older than 60 years at the University of Michigan's General Clinical Research Center. Hormone users had completed at least 10 continuous years of conjugated equine estrogens with or without medroxyprogesterone acetate, begun within 2 years of menopause. Women were excluded for illness, medication, intermittent estrogen use, phytoestrogen use, recent smoking, and MRI contraindications. The primary outcome was functional MRI-detected brain activity during the visual memory task. RESULTS: Compared with never users, both groups of hormone users had increased activation in the frontal and parietal cortices, insula, hippocampus, and cingulate; combined hormone users also had increased activation in the putamen and raphe (corrected P < 0.05 or uncorrected P < 0.001 with a priori hypothesis). Across the entire sample, the medial temporal cortex (P < 0.0001 right; P < 0.018 left) and right hippocampus (P < 0.0001) positively correlated with task performance. CONCLUSIONS: Hormone use was associated with increased brain activation during the visual memory task, in regions used for visual working memory. A positive correlation between activation and task performance suggests that early-initiation, long-term postmenopausal hormone use may benefit visual working memory.

Enhanced neuroactivation during verbal memory processing in postmenopausal women receiving short-term hormone therapy.

OBJECTIVE: To study the effects of hormone therapy on brain activation patterns during verbal memory in postmenopausal women. DESIGN: A randomized, double-blind placebo-controlled cross-over study was performed. SETTING: A tertiary care university medical center. PATIENT(S): Ten healthy postmenopausal women (age range 56-60 years) were recruited from the local community. INTERVENTION(S): Women were randomized to the order they received combined hormone therapy, 5 microg of ethinyl E(2) and 1 mg of norethindrone acetate, and placebo. Volunteers received hormone therapy or placebo for 4 weeks, followed by a 1-month washout period, and then received the other treatment for 4 weeks. A functional magnetic resonance imaging (fMRI) was performed at the end of each 4-week treatment using a verbal memory task. MAIN OUTCOME MEASURE(S): Brain activation patterns were compared between hormone therapy and placebo. RESULT(S): Hormone therapy was associated with increased activation in the left middle/superior frontal cortex (BA 6,9), medial frontal cortex and dorsal anterior cingulate (BA 24,32), posterior cingulate (BA 6), and left inferior parietal cortex (BA 40) during memory encoding. All regions were significant with correction for multiple comparisons. CONCLUSION(S): Hormone therapy increased neural activation in frontal and parietal areas in postmenopausal women during a verbal memory task.

Varying patterns of verbal recall, recognition, and response bias with progression of alzheimer's disease.

Aspects of performance on verbal list learning tasks, such as recall, recognition, and response bias, may vary with severity in Alzheimer's disease (AD). We administered a 10-item, single-category word list learning test using selective reminding procedures to 188 patients with probable AD and 36 healthy normal controls with equivalent age and education. We analyzed the total number of words recalled as well as discrimination and response bias indexes derived from signal detection theory. Recall and discrimination were impaired in patients with probable AD compared to controls, and recall scores were more sensitive to dementia severity than discrimination. While many AD patients showed a liberal response bias, their response bias varied considerably within patient groups and did not correlate with disease severity.