| Laboratory of Behavioral Neuroscience |
Intramural Program Investigators ^ Home ^ |
| Alan B. Zonderman, Ph.D., Senior Investigator Chief, Lifespan, Cognition and Health Section |
 Dr. Zonderman earned his undergraduate degree in Behavior Genetics from University of Massachusetts and his doctorate in Psychology from the University of Colorado. After a postdoctoral fellowship in multivariate statistics at the University of California, Berkeley, and academic positions at University of California, Davis and The Johns Hopkins University, he joined NIA as a Senior Staff Fellow in the Stress and Coping Section. Since 1997, he has been Chief of the Cognition Section in the Laboratory of Personality and Cognition. His research interests include individual differences in cognition and personality and their relationship with adult morbidity and mortality, predicting the onset of cognitive impairments and Alzheimer's disease, and the role of genetics in cognitive declines and personality. |
| Research Interests: Distinguishing Pathological from Normal Cognitive Aging: Research in the Lifespan, Cognition and Health Section focuses on distinguishing pathological from normal cognitive aging. The purpose of this research is to identify predictors of cognitive morbidity, and to identify which cognitive processes are preserved with aging and which processes are vulnerable to disease. An important effort of research in the Lifespan, Cognition and Health Section is focused on longitudinal research in the Baltimore Longitudinal Study of Aging (BLSA). Cognitive tests have been administered to participants in the BLSA since 1960. Some individuals presently in the study have as many as seven repeated assessments beginning in the 1960's. |
| The cognitive tests administered to participants in the BLSA reflect our primary interest in pathological cognitive impairments, especially Alzheimer's disease (AD). The cognitive testing program is divided into two batteries, one for longitudinal prediction and another for cognitive and neuropsychological outcomes. The longitudinal repetitions of these tests distinguish typical changes in performance associated with aging from changes in performance which may be associated with disease when combined with neurological and neuropsychological outcomes and clinical diagnoses of AD. |
| An increasingly important area of research in the Lifespan, Cognition and Health Section focuses on factors that reduce the risk of cognitive declines. An example of this focus is the finding that nonsteroidal anti-inflammatory drugs reduce the risk of Alzheimer's disease. Another example of this focus is based on recent findings that estrogen replacement therapy reduces the risk for both AD and cognitive declines in post-menopausal women. In an intervention study testing the effects of hormone replacement on cognition, we are examining the effects of estrogen and testosterone in older women and men in conjunction with structural and functional neuroimages. |
| Cognitive Declines in Aging Subjects Free of Dementing Diseases: In people with no signs of dementia, some cognitive abilities resist decline while other abilities show characteristic age-related changes beginning in the 50's or 60's. Research by investigators in the Lifespan, Cognition and Health Section has shown that vocabulary scores generally resist declines, and may increase slowly over time until there are small decreases after the eighth or ninth decades. Immediate visual memory shows a much different pattern of change. We found that errors in immediate visual recall increased exponentially with increased age in both cross-sectional and longitudinal analyses. |
| We also found that there were different rates of change in separate types of errors over time. Distortions, rotations, perseverations and mislocations were the most frequent errors across all ages. Although older participants made significantly greater errors regardless of error type, the greatest age differences were found for distortions and omissions. Men and women showed similar patterns of age-associated increases in errors, but there was a significant interaction between gender and error type indicating that women across all ages made more omissions and rotations, not other types of errors. Longitudinal analyses showed that distortions, omissions and rotations increased with age. Although women made more omission errors, men showed steeper increases with age. |
| Long-Term Predictions of Cognitive Impairment and Dementia: The onset of cognitive impairment is either a discrete event or a gradual process that manifests over time. We asked whether changes in previous test performance predict evidence of cognitive impairment assessed by the Mini-Mental Status Examination (MMSE) over relatively long intervals. We hypothesized that visual memory administered prior to the MMSE would significantly account for cognitive impairment after controlling for age at mental status exam and vocabulary score (a measure highly related to general intelligence). The correlations between visual memory and MMSE over 6-8 and 9-15 years were .36 and .34 (p < .05). These results provide preliminary evidence that mental status can be predicted, at least in part, by earlier performance on cognitive tests. Although the present findings are limited to only these cognitive tests, they provide important evidence that early signs of dementia may be detectable as many as 6-15 years prior to noticeable decline on mental status tests. |
| Six-year changes in immediate visual memory predicted Alzheimer's disease (AD) prior to its onset. Individuals with diagnoses of AD had larger changes in immediate memory performance over the six-year interval prior to the estimated onset of their disease than subjects without AD. Six-year longitudinal change in immediate visual memory performance also predicted subsequent cognitive performance 6-15 and 16-22 years later, even after adjusting for the influences of age, general ability, and initial immediate memory. These results provide evidence that change in immediate visual memory performance has long-term prognostic significance. These results further suggest that change in recent memory performance may be an important precursor of the development of the disease. |
| Analyses comparing BLSA participants who developed dementing illnesses with nondemented participants also showed that particular errors in visual memory may be more sensitive markers of impairment than others. More than 5 years before the onset of illness, demented individuals made more distortion errors than participants who did not develop dementing illnesses. In addition, individuals with signs of dementia had significantly greater rates of change in perseverations, rotations, and size errors compared with nondemented participants. These findings suggest that immediate visual memory is an important test for distinguishing normal from pathological cognitive decline and that specific types of errors in short-term memory may be important early markers of dementia. |
| Risks and Protective Factors for Cognitive Decline: If cognitive decline is an important predictor of pathological cognitive aging then it seems reasonable to investigate factors that decrease or increase the risk of cognitive decline. Estrogen replacement therapy (ERT) is increasingly recommended for postmenopausal women due to its potential beneficial effects on physical health in older women. The possibility of a protective effect on cognitive function has also been suggested. In the BLSA, women receiving hormone treatment at the time of testing made significantly fewer errors in immediate visual recall than women who were not on hormone therapy. Less memory change was found in women who started hormone therapy between examinations than women who never received hormone therapy. These findings support the notion that estrogen has a beneficial role on cognitive functioning in aging women. |
| We continue to extend our present studies on the risks and protective factors for cognitive declines and dementias. In particular, as we gather additional repeat data on which to base reliable measures of cognitive trajectories, we will relate apoE and other genotypic and genomic measures to determine whether there are critical periods of decline. In addition, we will examine the role of modulators of cognitive decline such as hypertension and hormone replacement therapy, particularly in conjunction with MRI anatomical and PET functional assessments. We will also examine chronicity of hypertension, adequacy of blood pressure control, and differential effects and interactions with other known risks such as apoE genotype. |
| Socioeconomic Status and Race: Little is known about the risks and rates of cognitive change as a function of socioeconomic status and race, particularly the extent to which health disparities moderate these relationships. We have initiated a new study, Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS). HANDLS is a multidisciplinary, prospective epidemiologic longitudinal study with which we hope to disentangle the relationships among race, socioeconomic status, and health outcomes. The study examines whether race and socioeconomic status influence health disparities in cardiovascular health, cerebrovascular health, and change in cognitive performance over time. HANDLS deploys a novel data collection paradigm by using mobile medical research vehicles. These vehicles serve as community-based platforms for clinical research, and we use them as tools for creating effective methods for recruiting and retaining non-traditional research participants into age-related clinical research. Although we expect data collection to begin in 2004, pilot studies have demonstrated the utility of using mobile medical research vehicles in the community. |
| Contact Information:
Laboratory of Behavioral Neuroscience Biomedical Research Center, room 04B136 251 Bayview Boulevard, Suite 100 Baltimore, MD 21224-6825 Phone 410-558-8280 Fax 410-558-8281 E mail zonderman@nih.gov For more information about the Laboratory: http://www.irp.nia.nih.gov/branches/lpc/cs.htm |
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