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1.  Temporal Relationships between Depressive Symptoms and White Matter Hyperintensities in Older Men and Women 
International journal of geriatric psychiatry  2012;28(1):10.1002/gps.3791.
Objective
Associations between vascular disease and depression in late life, including increased white matter hyperintensities (WMHs), have been reported. Whether depression is an etiology or a consequence of vascular disease is still unknown. We investigated the temporal relationship between depressive symptoms and WMHs in older men and women.
Methods
We utilized data from 90 dementia-free older adults (39 women, 51 men), 57 years of age and older at baseline, from the neuroimaging substudy of the Baltimore Longitudinal Study of Aging. Participants were followed for up to 8 years. Ratings of white matter disease burden were available for the first, last, and at least one interim visit, and participants completed the Center for Epidemiologic Studies Depression Scale (CES-D) annually. Statistical models, performed separately in men and women, examined whether depressive symptoms predicted subsequent WMH ratings or WMHs predicted subsequent depressive symptoms.
Results
The total CES-D score was not associated with WMHs in men or women. In men, the CES-D depressed mood subscale predicted accelerating longitudinal increases in WMHs at older ages, but WMHs did not predict subsequent depressive symptoms. In women, there were no significant associations between the CES-D depressed mood subscale and WMHs.
Conclusions
White matter disease may be a consequence of depressed mood in men but not in women. Intervention strategies for depression may slow the progression of white matter disease in older men. These results add to previous findings documenting sex differences in the correlates of depressive disorders in late life.
doi:10.1002/gps.3791
PMCID: PMC3851322  PMID: 22415749
depression; aging; elderly; vascular disease; sex differences; longitudinal studies
2.  Treatment of word-finding deficits in fluent aphasia through the manipulation of spatial attention: Preliminary findings 
Aphasiology  2007;22(1):103-113.
Background
Attention, the processing of one source of information to the exclusion of others, is important for most cognitive processes, including language. Evidence suggests not only that dysfunctional attention mechanisms contribute to language deficits after stroke, but also that orienting attention to a patient's ipsilesional hemispace recruits attention mechanisms in the intact hemisphere and improves language functions in some persons with aphasia.
Aims
The aim of the current research was to offer proof of concept for the strategy of improving picture-naming performance in fluent aphasia by moving stimuli into the left hemispace. It was hypothesised that repeated orientation of attention to the ipsilesional hemispace during picture naming would lead to improved naming accuracy for participants with fluent aphasia.
Methods & Procedures
Three participants with stable fluent aphasia received daily treatment sessions that consisted of naming simple line drawings presented 45 degrees to the left of body midline on a computer monitor. Naming probes were administered before initiation of the treatment protocol to establish a baseline, and before each treatment session to measure change during treatment. The C statistic was used to establish the stability of baseline performance and to determine whether the slope of the treatment phases differed significantly from the slope of the baseline.
Outcomes & Results
Two of the three participants showed significant improvement over baseline performance in the percent correct of naming probes. One participant showed no improvement over baseline accuracy.
Conclusions
Results suggest that engaging right-hemisphere attention mechanisms may improve naming accuracy in some people with fluent aphasia. Findings justify further investigation of this treatment in a larger controlled study.
doi:10.1080/02687030600990983
PMCID: PMC3225083  PMID: 22131638
3.  Recurrent depressive symptoms and the incidence of dementia and mild cognitive impairment 
Neurology  2010;75(1):27-34.
Objective:
A history of depression has been linked to an increased dementia risk. This risk may be particularly high in recurrent depression due to repeated brain insult. We investigated whether there is a dose-dependent relationship between the number of episodes of elevated depressive symptoms (EDS) and the risk for mild cognitive impairment (MCI) and dementia.
Methods:
A total of 1,239 older adults from the Baltimore Longitudinal Study of Aging were followed for a median of 24.7 years. Diagnoses of MCI and dementia were made based on prospective data. Participants completed the Center for Epidemiologic Studies Depression Scale at 1- to 2-year intervals and were considered to have an EDS if their score was ≥16. Kaplan-Meier survival curves, log-rank test for trend for survivor functions, and Cox proportional hazards models were conducted to examine the risk of MCI and dementia by number of EDS.
Results:
We observed a monotonic increase in risk for all-cause dementia and Alzheimer disease as a function of the number of EDS. Each episode was associated with a 14% increase in risk for all-cause dementia. Having 1 EDS conferred an 87%–92% increase in dementia risk, while having 2 or more episodes nearly doubled the risk. Recurrence of EDS did not increase the risk of incident MCI.
Conclusions:
Our findings support the hypothesis that depression is a risk factor for dementia and suggest that recurrent depression is particularly pernicious. Preventing the recurrence of depression in older adults may prevent or delay the onset of dementia.
GLOSSARY
= Alzheimer disease;
= Baltimore Longitudinal Study of Aging;
= Clinical Dementia Rating;
= Center for Epidemiologic Studies Depression Scale;
= confidence interval;
= Dementia Questionnaire;
= depressive symptoms;
-
= Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised;
= elevated depressive symptoms;
= hazard ratio;
= mild cognitive impairment.
doi:10.1212/WNL.0b013e3181e62124
PMCID: PMC2906403  PMID: 20603482
4.  Frontal Atrophy and Attention Deficits in Older Adults with a History of Elevated Depressive Symptoms 
Brain imaging and behavior  2009;3(4):358.
Studies of older adults with depressive disorders indicate greater cognitive deficits and brain alterations than would be expected for their age. There is some evidence that these findings are present after a single episode of depression, but this work has been cross-sectional in nature. We investigated both cross-sectional and longitudinal associations between a history of elevated depressive symptoms (HDS), frontal lobe volumes, and cognitive performance within the context of normal age-related changes over time in the Baltimore Longitudinal Study of Aging. After controlling for age, HDS was associated with smaller total frontal gray matter volumes and with smaller regional volumes in the cingulate gyrus and orbitofrontal cortex. Men, but not women, with HDS showed deficits in auditory attention span at older ages. Results confirm previous reports that even a single episode of depression is associated with adverse outcomes in older adults but suggest that HDS does not affect longitudinal trajectories of cognitive and brain volume change.
PMCID: PMC2818329  PMID: 20161651
late-life depression; magnetic resonance imaging; aging; longitudinal studies; sex differences
5.  Unique and interactive effect of anxiety and depressive symptoms on cognitive and brain function in young and older adults 
Journal of depression & anxiety  2014;Suppl 1:22565.
Objective
Depression and anxiety and are associated with cognitive deficits and brain changes, especially in older adults. Despite the frequent co-occurrence of these conditions, cognitive neuroscience studies examining comorbid depression and anxiety are limited. The goal of the present study was to examine the unique and combined effect of depressive and anxiety symptoms on cognitive and brain functioning in young and older adults.
Methods
Seventy-one healthy, community-dwelling adults between the ages of 18 and 81 were administered a neuropsychological battery and completed the Center for Epidemiologic Studies Depression Scale (CES-D) and the trait form of the State-Trait Anxiety Inventory (STAI-T). A subset of 25 participants also underwent functional magnetic resonance imaging (fMRI) scanning while completing the n-back working memory task.
Results
Total depressive symptoms, depressed mood symptoms, and somatic symptoms were associated with deficits in speed, working memory and executive functions, especially in older adults. Symptoms of lack of well-being were not associated with any neuropsychological test. Anxiety was associated with better attention and working memory. Moreover, anxiety modified the relationship between depressive symptoms and executive functioning in older adults, as elevated depressive symptoms were associated with worse performance at low levels of anxiety, but not at higher anxiety levels. Similarly, analysis of fMRI data showed that total depressive symptoms and depressed mood symptoms were associated with decreased activity in the superior frontal gyrus at low anxiety levels, but not at high anxiety levels.
Conclusion
Results confirm previous reports that subthreshold depression and anxiety impact cognitive and brain functioning and suggest that the interaction of depression and anxiety results in distinct cognitive and brain changes. Findings highlight the importance of assessing and controlling for symptoms of depression and anxiety in research studies of either condition.
doi:10.4172/2167-1044.S1-003
PMCID: PMC4222514  PMID: 25383262
6.  Within-session Practice Eliminates Age Differences in Cognitive Control 
Previous research employing short-term practice and long-term training have been successful in reducing cognitive control deficits in the elderly. The goal of this study was to examine the effect of practice within session on a demanding cognitive control task. Nineteen older adults and 16 young adults performed 720 trials of a cued version of the Stroop task, in which an instructional cue is presented before each individually presented Stroop stimulus. Statistical analyses focused on the most difficult color-naming condition in task-switching blocks. Overall, participants showed faster reaction times and decreased errors with practice, particularly on incongruent trials. Older adults showed a greater reduction in errors with practice than young adults. Moreover, older adults, but not young adults, showed a reduction in errors and reaction times with practice on incongruent trials. Findings further suggest that practice reduces age-related differences in cognitive control. Improvements in cognitive control functioning has implications for treating functional deficits in older adults.
doi:10.1080/13825585.2012.736469
PMCID: PMC3655128  PMID: 23116428
Aging; Cognitive Control; Practice; Stroop task
7.  The Neural Correlates of Neuroticism Differ by Sex and Prospectively Mediate Depressive Symptoms Among Older Women 
Journal of affective disorders  2010;127(1-3):241-247.
Background
Mood disorders in old age increase the risk of morbidity and mortality for individuals and healthcare costs for society. Trait Neuroticism, a strong risk factor for such disorders into old age, shares common genetic variance with depression, but the more proximal biological mechanisms that mediate this connection are not well understood. Further, whether sex differences in the neural correlates of Neuroticism mirror sex differences in behavioral measures is unknown. The present research identifies sex differences in the stable neural activity associated with Neuroticism and tests whether this activity prospectively mediates Neuroticism and subsequent depressive symptoms.
Methods
A total of 100 (46 female) older participants (>55 years) underwent a resting-state PET scan twice, approximately two years apart, and completed measures of Neuroticism and depressive symptoms twice.
Results
Replicating at both time points, Neuroticism correlated positively with resting-state regional cerebral blood-flow activity in the hippocampus and midbrain in women and the middle temporal gyrus in men. For women, hippocampal activity mediated the association between Neuroticism at baseline and depressive symptoms at follow-up. The reverse mediational model was not significant.
Conclusions
Neuroticism was associated with stable neural activity in regions implicated in emotional processing and regulation for women but not men. Among women, Neuroticism prospectively predicted depressive symptoms through greater activity in the right hippocampus, suggesting one neural mechanism between Neuroticism and depression for women. Identifying responsible mechanisms for the association between Neuroticism and psychiatric disorders may help guide research on pharmacological interventions for such disorders across the lifespan.
doi:10.1016/j.jad.2010.06.004
PMCID: PMC3023236  PMID: 20599276
Neuroticism; Depression; PET Imaging; Hippocampus; Mediation; Sex differences
8.  Internal Consistency and Test-Retest Stability of the Geriatric Depression Scale-Short Form in African American Older Adults 
The Geriatric Depression Scale (GDS) is one of the most widely used self-rated mood questionnaires for older adults. It is highly correlated with clinical diagnoses of depression and has demonstrated validity across different patient populations. However, the reliability of the GDS among African American older adults remains to be firmly established. In a baseline sample of 401 African American adults age 51 and over, the GDS-15 item short form demonstrates good internal consistency (KR20=.71). Stability over a 15-month interval in a retest sample of 51 adults is deemed adequate (r=.68). These findings support the use of the GDS-15 item short form as a reliable mood questionnaire among African American older adults.
doi:10.1007/s10862-008-9123-z
PMCID: PMC2794552  PMID: 20161488
Geriatric depression scale; GDS; Depression; African American; Reliability
9.  Longitudinal Study of Chronic Depressive Symptoms and Regional Cerebral Blood Flow in Older Men and Women 
Objectives
Late-life depression is associated with alterations in regional cerebral blood flow (rCBF) and metabolism in a neural network that includes frontostriatal and limbic regions and the cerebellum. Prior studies suggest that clinical depression and subthreshold depressive symptoms (SDS) are associated with similar cognitive deficits and structural brain changes, but little is known about the relationship between SDS and patterns of brain activity. Additionally, the neural correlates of depression have not been fully explored in men and women separately. This study investigated cross-sectional and longitudinal relationships between SDS and rCBF in older men and women.
Methods
Sixty-one dementia-free older adults (35 men, 26 women), 56 years of age and older at baseline, from the neuroimaging substudy of the Baltimore Longitudinal Study of Aging participated. Participants underwent resting-state PET scans at baseline and at year 9 and completed the Center for Epidemiologic Studies Depression Scale annually.
Results
At eight-year follow-up, both men and women showed cross-sectional associations between mean depressive symptom scores and activity in primarily frontal and temporal regions and the cerebellum. Higher average depressive symptoms were associated with longitudinal rCBF decreases in frontal regions in both men and women, and in temporal regions in men.
Conclusion
Regions showing associations between activity and SDS were similar to those found in studies of clinical depression, providing support for the hypothesis that depressive syndromes exist on a continuum of severity. Sex differences in associations provide some evidence that the pathophysiology of depressive disorders differs between men and women.
doi:10.1002/gps.2298
PMCID: PMC2744107  PMID: 19484709
subthreshold depression; late-life depression; sex differences; positron emission tomography; aging; longitudinal studies
10.  Effects of Race and Socioeconomic Status on the Relative Influence of Education and Literacy on Cognitive Functioning 
Previous research has shown that reading ability is a stronger predictor of cognitive functioning than years of education, particularly for African Americans. The current study was designed to determine whether the relative influence of literacy and education on cognitive abilities varies as a function of race or socioeconomic status (SES). We examined the unique influence of education and reading scores on a range of cognitive tests in low and high SES African Americans and Whites. Literacy significantly predicted scores on all but one cognitive measure in both African American groups and in low SES Whites, while education was not significantly associated with any cognitive measure. In contrast, both education and reading scores predicted performance on many cognitive measures in high SES Whites. These findings provide further evidence that reading ability better predicts cognitive functioning than years of education and suggest that disadvantages associated with racial minority status and low SES affect the relative influence of literacy and years of education on cognition.
doi:10.1017/S1355617709090821
PMCID: PMC2722437  PMID: 19573276
reading; income; demographics; ethnicity; neuropsychological testing; cognition
11.  Depressive symptoms and brain volumes in older adults: a longitudinal magnetic resonance imaging study 
Background
Late-life depression is associated with decreased brain volumes, particularly in frontal and temporal areas. Evidence suggests that depressive symptoms at a subclinical level are also associated with brain atrophy in these regions, but most of these associations are based on cross-sectional data. Our objective was to investigate both cross-sectional and longitudinal relations between sub-threshold depressive symptoms and brain volumes in older adults and to examine whether these associations are modified by age.
Methods
In total, 110 dementia-free adults from the neuroimaging substudy of the Baltimore Longitudinal Study of Aging aged 56 years and older at baseline participated in this study. Participants received annual evaluations for up to 9 years, during which structural magnetic resonance imaging (MRI) scans were acquired and depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale.
Results
Mean depressive symptom scores over time were associated with grey matter volume reductions in the left temporal lobe. Depressive symptoms were associated with brain volume reductions with advancing age in the cingulate gyrus and orbitofrontal cortex. Moreover, individuals with higher mean depressive symptom scores showed a faster rate of volume decline in left frontal white matter. Depressive symptoms were not associated with hippocampus volumes.
Limitations
Limitations include the relative homogeneity of our primarily white and highly educated sample, the lack of information about age at onset of depressive symptoms and potential limitations of the automated brain volume registration.
Conclusion
Our results suggest that depressive symptoms, even at a subthreshold level, are associated with volume reductions in specific frontal and temporal brain regions, particularly with advancing age.
PMCID: PMC2732743  PMID: 19721847
12.  Differential Association of Concurrent, Baseline, and Average Depressive Symptoms with Cognitive Decline in Older Adults 
Objectives
The impact of depressive symptoms on cognitive decline in older adults remains unclear due to inconsistent findings in the literature. It is also unclear whether effects of depressive symptoms on cognitive decline vary with age. This study investigated the effect of concurrent, baseline, and average depressive symptoms on cognitive functioning and decline, and examined the interactive effect of age and depressive symptoms on cognition.
Design
Prospective observational design with examination of cognitive performance and depressive symptoms at 1–2 year intervals for up to 26 years.
Setting
Baltimore Longitudinal Study of Aging, National Institute on Aging.
Participants
1, 586 dementia-free adults 50 years of age and older.
Measurements
Scores over time on the Center for Epidemiologic Studies Depression Scale and measures of learning and memory, attention and executive functions, verbal and language abilities, visuospatial functioning, and general cognitive status.
Results
Increased depressive symptoms were associated with poor cognitive functioning and cognitive decline in multiple domains. Concurrent, baseline, and average depressive symptoms had differential associations with cognition. Average depressive symptoms, a measure of chronic symptoms, appeared to show the most widespread effects on cognitive abilities. Effects of depressive symptoms on some frontal functions were greater with advancing age.
Conclusion
Depressive symptoms are associated with poor cognitive functioning and cognitive decline, particularly with advancing age. The widespread impact of average depressive symptoms on cognition suggests that clinicians should consider the chronicity of depressive symptoms when evaluating cognitive functioning in older adults.
doi:10.1097/JGP.0b013e3181662a9c
PMCID: PMC2405887  PMID: 18378557
aging; sub-clinical depression; cognition

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