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P M Maki

Publications and source records attributed to P M Maki.

8 recordsLinked to original sources

Effects of estrogen on patterns of brain activity at rest and during cognitive activity: a review of neuroimaging studies.

Animal and human studies provide evidence of systematic effects of estrogen on cerebral activity and cognitive function. In this article, we review studies of the activational effects of estrogen on cerebral activity during rest and during the performance of cognitive tasks in pre- and postmenopausal women. The goal is twofold--to better understand evidence suggesting that estrogen influences brain functioning and argue for the importance of considering hormone effects when designing neuroimaging studies. Hormone-related increases in blood flow during the resting state have been documented in healthy elderly women, elderly women with cerebrovascular disease, and middle-aged postmenopausal women with early menopause. There is no reliable influence of estrogen on blood flow during the resting state in women with Alzheimer's disease. Hormone therapy has been associated with changes in brain activation patterns in middle-aged and elderly postmenopausal women during performance of verbal and figural memory tasks, providing critical biological support for the view that estrogen might protect against age-associated changes in cognition and lower the risk of Alzheimer's disease. There is a paucity of studies examining changes in brain activation patterns across the menstrual cycle and a need for randomized studies of hormone therapy in postmenopausal women to confirm findings from observational studies. General procedural guidelines for controlling and investigating hormone effects in neuroimaging studies are discussed.

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Effects of hormone replacement therapy on cognitive and brain aging.

Recent reports suggest that hormone therapy may be associated with a reduced risk for Alzheimer's disease and may offer some protection against age-associated declines in specific cognitive functions. The majority of these reports are based on observational studies, which are confounded by the "healthy user" bias--the tendency for women receiving hormone therapy to be younger, better educated, and have fewer medical problems. In one attempt to address these limitations, we conducted a series of studies examining effects of hormone therapy on cognitive and brain functioning in nondemented postmenopausal women in the Baltimore Longitudinal Study of Aging (BLSA). In this sample, women receiving hormone therapy and women who never received hormone therapy were comparable with respect to educational attainment, general medical health, and performance on a test of verbal knowledge. Despite these similarities, women receiving hormone therapy performed better on tests of verbal and visual memory compared to never-treated women. The two groups also differed in the patterns of regional brain activation evoked during performance of delayed verbal and figural memory tasks. Furthermore, longitudinal comparisons revealed greater relative blood flow increases over two years in women receiving hormone therapy for the hippocampus and other mesial temporal lobe structures that subserve memory. These observational findings from our studies in the BLSA have led to the development of a large-scale randomized clinical trial of hormone therapy and cognitive aging, the ancillary Women's Health Initiative Study of Cognitive Aging (WHISCA), and have important implications for studies of the effects of SERM's on cognitive and brain functioning.

Aging↗

Enhanced verbal memory in nondemented elderly women receiving hormone-replacement therapy.

OBJECTIVE: This study examined the effects of hormone-replacement therapy on memory and other cognitive abilities in cognitively intact older women. METHOD: This prospective observational study in nondemented postmenopausal women aged 50-89 from the Baltimore Longitudinal Study of Aging involved study groups consisting of 103 women who were receiving oral or transdermal estrogen-replacement therapy (44 of whom were receiving adjuvant progesterone) and 81 women who had never received such therapy. Groups were naturally matched on education, health status, depressive symptoms, annual income, and general verbal ability. To restrict the study group to cognitively healthy women, prospective clinical data were used to exclude women who developed dementia up to 5 years after assessment. Data were cross-sectional. Multivariate analysis of variance and follow-up univariate analyses of variance were performed to compare those women who were receiving and those who had never received hormone-replacement therapy on measures of verbal memory, figural memory, mental rotations, attention, and working memory. RESULTS: The women receiving hormone-replacement therapy performed significantly better on measures of verbal learning and memory than did those who had never received hormones, but there were no significant differences in scores on other cognitive tests. Specific aspects of memory performance, including encoding and retrieval, were superior among the women receiving hormone therapy. CONCLUSIONS: These findings, based on groups of women who were receiving and had never received hormone-replacement therapy and who were naturally matched on health and cognitive status, suggest that hormone-replacement therapy may have a selective beneficial effect on verbal memory in older nondemented women.

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Conceptual and perceptual implicit memory in Huntington's disease.

The aims of this study were to examine and compare perceptual and conceptual implicit memory (CIM) in Huntington's disease (HD) and to characterize the relationship between tests of frontal lobe functioning and CIM. Sixteen HD patients and 16 normal controls completed structurally parallel tests of perceptual implicit memory and CIM (i.e., rhyme and category exemplar generation), tests of explicit memory, and verbal fluency. HD patients showed intact implicit memory for both rhyme and category exemplars, despite evidence of frontal dysfunction on other tests. An unexpected finding was that patients showed a deficit in cued rhyme generation that correlated with severity of neurological impairment. The authors replicated findings in controls of a correlation between letter fluency and CIM but found no relationship in patients. Frontal dysfunction in HD may lessen the influence of generative strategies on tests of CIM without compromising performance.

Adult↗

Age differences in implicit memory: fragmented object identification and category exemplar generation.

In a cross-sectional study of 164 participants aged 21 to 91, the authors examined age differences on two implicit tests, fragmented object identification (FOI) and category exemplar generation (CEG), and on tests of explicit memory, attention, and verbal fluency. FOI results revealed impaired perceptual skill learning in those over 60 and a decrease in perceptual priming across young, middle-aged, and older groups. CEG priming was impaired in those over 80. Regression analysis revealed explicit contamination of priming on both the FOI and CEG tests. Across the three implicit measures, age accounted for 4 to 13% of the variance when explicit memory was controlled. Semantic fluency predicted CEG priming, suggesting possible frontal lobe involvement on the test. Altogether, results indicate that age has a small but reliable influence on implicit memory.

Adult↗

Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance.

Reports that estrogen may protect against age-associated memory decline and Alzheimer's Disease have kindled interest in the effects of estrogen replacement therapy (ERT) on cognition and brain function. As part of a 9-year study in the Baltimore Longitudinal Study of Aging, we are performing annual magnetic resonance imaging, positron emission tomography (PET), and neuropsychological assessments to examine brain structure and function in individuals aged 55 and older. PET measurements of regional cerebral blood flow (rCBF) are obtained under 3 conditions: rest and verbal and figural delayed recognition memory tasks. Fifteen women receiving ERT (with or without the addition of progesterone) were compared with a matched sample of 17 untreated women. There were no significant differences between groups in regional brain volumes or ventricular size. However, ERT users and nonusers showed significant differences in PET-rCBF relative activation patterns during the memory tasks. During verbal memory processing, there were significant interactions in rCBF activations for the right parahippocampal gyrus, right precuneus, right frontal regions, and left hypothalamus. During figural memory processing, significant interactions were observed for right parahippocampal and inferior parietal regions and for left visual association and anterior thalamic regions. ERT users also showed better performance on neuropsychological tests of figural and verbal memory and on some aspects of the PET activation tests, although the two groups did not differ in education, overall verbal ability, or performance on other neuropsychological tests. These findings confirm our previous observation of the beneficial effects of ERT on figural memory. Moreover, differences in rCBF activation patterns between ERT users and nonusers suggest an area for future research to examine mechanisms through which ERT may influence memory and other cognitive abilities.

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Effect of amantadine hydrochloride on symptoms of frontal lobe dysfunction in brain injury: case studies and review.

Symptoms consistent with dysfunction of the frontal lobes can occur following traumatic brain injury (TBI) or other types of acquired brain injury (stroke, aneurysm). These symptoms can include problems with short-term memory, attention, planning, problem solving, impulsivity, disinhibition, poor motivation, and other behavioral and cognitive deficits ("frontal lobe syndrome"). These symptoms may respond to certain drugs, such as dopaminergic agents. This case series describes results of using amantadine in 7 patients with this type of symptom profile (6 with TBI, 1 with meningitis following sinus surgery). Patients received neuropsychiatric examinations and serial neuropsychological testing. All patients showed some degree of positive response. One had side effects that resolved upon discontinuation of drug. The rationale for using dopaminergics is discussed, and pertinent literature is reviewed.

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Longitudinal effects of estrogen replacement therapy on PET cerebral blood flow and cognition.

Observational studies suggest that estrogen replacement therapy (ERT) may protect against age-related memory decline and lower the risk of Alzheimer's disease (AD). This study aimed to characterize the neural substrates of those effects by comparing 2-year longitudinal changes in regional cerebral blood flow (rCBF) in 12 ERT users and 16 nonusers. Positron emission tomography (PET) measurements of rCBF were obtained under three conditions: rest, and verbal and figural recognition memory tasks. Groups showed different patterns of change in rCBF over time in a number of brain areas. These group differences, for the most part, reflected regions of increased rCBF over time in users compared to nonusers. The greatest differences between ERT users and nonusers were in the hippocampus, parahippocampal gyrus, and temporal lobe, regions that form a memory circuit and that are sensitive to preclinical AD. Across a battery of standardized neuropsychological tests of memory, users obtained higher scores than did nonusers of comparable intellect. Group differences in longitudinal change in rCBF patterns may reflect one way through which hormones modulate brain activity and contribute to enhanced memory performance among ERT users.

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