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Biomedical subjects

Helen Lavretsky

Publications and source records attributed to Helen Lavretsky.

At least 19 recordsLinked to original sources
PubMed2006

PET of brain amyloid and tau in mild cognitive impairment.

BACKGROUND: Amyloid senile plaques and tau neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease that accumulate in the cortical regions of the brain in persons with mild cognitive impairment who are at risk for Alzheimer's disease. Noninvasive methods to detect these abnormal proteins are potentially useful in developing surrogate markers for drug discovery and diagnostics. METHODS: We enrolled 83 volunteers with self-reported memory problems who had undergone neurologic and psychiatric evaluation and positron-emission tomography (PET). On the basis of cognitive testing, 25 volunteers were classified as having Alzheimer's disease, 28 as having mild cognitive impairment, and 30 as having no cognitive impairment (healthy controls). PET was performed after injection of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro. All subjects also underwent 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET, and 72 underwent magnetic resonance imaging (MRI). RESULTS: Global values for FDDNP-PET binding (average of the values for the temporal, parietal, posterior cingulate, and frontal regions) were lower in the control group than in the group with mild cognitive impairment (P<0.001), and the values for binding in the group with mild cognitive impairment were lower than in the group with Alzheimer's disease (P<0.001). FDDNP-PET binding differentiated among the diagnostic groups better than did metabolism on FDG-PET or volume on MRI. CONCLUSIONS: FDDNP-PET scanning can differentiate persons with mild cognitive impairment from those with Alzheimer's disease and those with no cognitive impairment. This technique is potentially useful as a noninvasive method to determine regional cerebral patterns of amyloid plaques and tau neurofibrillary tangles.

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PubMed2006

Executive dysfunction and memory in older patients with major and minor depression.

Executive function, known to be impaired during late-life depression, is dependent on frontostriatal pathways. Memory is also frequently observed to be impaired among late-life depressed patients, so we assessed the possibility that executive function mediates the learning and recall deficit as a "downstream" effect of the frontostriatal compromise in executive function. A cross-sectional sample of minor and major depressed patients (N=95) and nondepressed volunteers (N=71), screened for other Axis I disorders, dementia, medical comorbidity, and severity of depression, completed a neuropsychological battery that included the California Verbal Learning Test and other tests selected for convergent and divergent validity testing. Depressed patients differed from controls on learning the word list and on verbal and nonverbal executive tasks. Executive function was a mediator for depressed patients verbal learning scores (z=-2.67, p=.01). A nonverbal executive score also mediated verbal learning (z=-2.18, p=.03) indicating convergent validity of executive dysfunction during verbal learning exercises. In conclusion, the verbal memory deficits typically attributed to late-life depression may result from impaired executive functioning during the learning phase of the recall task.

Age of Onset↗
PubMed2006

Methylphenidate-enhanced antidepressant response to citalopram in the elderly: a double-blind, placebo-controlled pilot trial.

OBJECTIVE: The authors evaluated the potential of methylphenidate to accelerate and enhance antidepressant response to citalopram in elderly depressed patients. METHODS: Sixteen outpatients with major depression were treated in a 10-week double-blind trial. Response was defined as a score on the Hamilton Depression Rating Scale (24-item) of less than 10. RESULTS: An accelerated response was observed by week 3 in five subjects receiving citalopram (CIT)+methylphenidate (MPH) and in none of those receiving CIT+placebo (PBO). Subjects receiving citalopram and methylphenidate showed a significant improvement in depressive symptoms compared with those on citalopram and placebo. CONCLUSION: Combined treatment with citalopram and methylphenidate appears to be a viable strategy for accelerating and enhancing antidepressant response in elderly depressed patients limited by tolerability and safety.

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PubMed2006

Effects of a 14-day healthy longevity lifestyle program on cognition and brain function.

OBJECTIVE: The objective of this study was to determine the effects of a 14-day healthy longevity lifestyle program on cognition and cerebral metabolism in people with mild age-related memory complaints. METHODS: Seventeen nondemented subjects, aged 35-69 years (mean: 53 years, standard deviation: 10) with mild self-reported memory complaints but normal baseline memory performance scores were randomly assigned to 1) the intervention group (N = 8): a program combining a brain healthy diet plan, relaxation exercises, cardiovascular conditioning, and mental exercise (brain teasers and verbal memory training techniques); or 2) the control group (N = 9): usual lifestyle routine. Pre- and postintervention measures included self-assessments of memory ability, objective tests of cognitive performance, and determinations of regional cerebral metabolism during mental rest with [fluorine-18]fluorodeoxyglucose (FDG) positron emission tomography (PET). RESULTS: Subjects in the intervention group objectively demonstrated greater word fluency. Concomitantly, their FDG-PET scans identified a 5% decrease in activity in the left dorsolateral prefrontal cortex. The control group showed no significant change in any of the measures. CONCLUSIONS: A short-term healthy lifestyle program combining mental and physical exercise, stress reduction, and healthy diet was associated with significant effects on cognitive function and brain metabolism. Reduced resting activity in left dorsolateral prefrontal cortex may reflect greater cognitive efficiency of a brain region involved in working memory.

Adult↗
PubMed2006

Innovations: geriatric psychiatry: diagnosis and treatment of neuropsychiatric symptoms in Alzheimer's disease.

The authors review research on the treatment of behavioral disturbances and psychiatric symptoms of patients with dementia, including pharmacological treatment with antipsychotics, antidepressants, cholinesterase inhibitors, and other psychotropic drugs. They conclude that although these medications have some beneficial effects, no intervention is currently able to eradicate behavioral disturbances and psychiatric symptoms of demented patients. Research suggests that multiple interventions for an individual patient are likely to replace the use of a single treatment. Such interventions include caregiver training and support, antipsychotics, antidepressants, and cholinesterase inhibitors, along with other drugs developed for the treatment of Alzheimer's disease.

Alzheimer Disease↗
PubMed2005

Estrogen use and brain metabolic change in postmenopausal women.

OBJECTIVE: We used positron emission tomography to evaluate cerebral glucose metabolic change in postmenopausal women in a naturalistic observational study. METHOD: Women estrogen users (n = 11) and non-users (n = 9) were studied at baseline and 2 years later. Analyses focused on glucose metabolism in regions previously reported to decline in older persons at risk for Alzheimer's disease (AD) (posterior cingulate and lateral temporal cortex). RESULTS: Region of interest (ROI) analysis at baseline showed no regional differences between women estrogen users and non users. ROI follow-up analysis revealed that women non-users declined significantly in the posterior cingulate cortex (P= 0.04). Statistical parametric mapping (SPM) analysis confirmed a significant decrease in metabolism of the posterior cingulate cortex among non-users at 2-year follow-up (P = 0.004). In contrast, women estrogen users did not exhibit significant metabolic change in the posterior cingulate. CONCLUSIONS: Estrogen use may preserve regional cerebral metabolism and protect against metabolic decline in postmenopausal women, especially in posterior cingulate cortex, the region of the brain found to decline in the earliest stages of AD.

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PubMed2005

Antidepressant exposure may protect against decrement in frontal gray matter volumes in geriatric depression.

OBJECTIVES: Depressed elderly patients with and without antidepressant exposure were compared to normal controls to examine the effects of prior antidepressant exposure on regional brain gray matter volumes using magnetic resonance imaging (MRI). METHOD: The study was conducted from October 1999 to January 2003. Patients and controls were closely matched by age and education. They underwent comprehensive neuropsychiatric and physical examinations. Measures of the total frontal lobe and the frontal gray and white matter volumes corrected by the intracranial volume were obtained using MRI, together with clinical measures of medical burden. Historical information about prior exposure to antidepressant drugs was collected using multiple information sources. The groups were compared using multivariate analyses of covariance, controlling for age, sex, and medical burden. RESULTS: The study sample comprised 41 patients who met the DSM-IV criteria for major depressive disorder (32 women; 11 antidepressant exposure and 30 drug-naive; mean age 70.5 years) and 41 controls (20 women; mean age 72.2 years). In the multivariate analysis, the depressed group had smaller corrected orbitofrontal cortex (OFC) total and gray matter volumes compared to the controls (p < .01). However, depressed patients with prior antidepressant exposure had larger OFC gray matter volumes compared to drug-naive depressed patients, but smaller than those in normal controls (p = .005). This effect was not explained by the group differences in sex ratio, age at onset of depression, or the number or duration of depressive episodes. CONCLUSIONS: We observed larger OFC regional volumes in depressed patients exposed to antidepressants compared to the drug-naive depressed subjects, but smaller than those in age-matched controls. Antidepressant exposure may protect against gray matter loss in geriatric depression.

Age Factors↗
PubMed2004

Mapping brain size and cortical gray matter changes in elderly depression.

BACKGROUND: In elderly depression, volumetric brain imaging findings suggest abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the hippocampus. No studies to date have mapped cortical abnormalities over the entire brain surface in major depression. Here, we conducted detailed spatial analyses of brain size and gray matter within the cortical mantle in elderly patients with major depression. METHODS: High-resolution, three-dimensional, structural magnetic resonance imaging data and cortical pattern matching methods were used in 24 depressed elderly patients and 19 group-matched controls to measure local brain size and proportions of gray matter at thousands of homologous cortical surface locations. RESULTS: Prominent brain size reductions were observed in the depressed subjects in the orbitofrontal cortex bilaterally. Cortical gray matter measurements revealed significant gray matter increases in the orbitofrontal cortex, adjacent to focal trend level significant decreases of gray matter in the same region. Depressed patients also exhibited significant gray matter increases in parietal cortices, as well as the left temporal cortex. CONCLUSIONS: Complex cortical changes may contribute to the brain size reduction of the orbitofrontal cortex and to the gray matter abnormalities detected in orbitofrontal cortex and temporoparietal cortices, thereby providing a potentially new window into the pathophysiology of elderly depression.

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PubMed2004

The significance of subsyndromal depression in geriatrics.

Clinically significant non-major depression has been underinvestigated, despite its high prevalence and public health impact. Although there is increasing recognition of the importance of subsyndromal forms of depression, their nosologic boundaries and neurobiologic mechanisms remain largely unknown. This review discusses the literature pertaining to the current concepts, phenomenology, neurobiology, and treatment approaches for geriatric non-major clinically significant depression. The authors examine the similarities and differences between various subtypes of depressive disorders, and compare non-major clinically significant depression in the elderly with non-geriatric adult populations. The authors draw conclusions from the published literature and present clinical criteria for the diagnosis of clinically significant non-major depression in the elderly.

Age Factors↗
PubMed2004

Executive dysfunction and visuospatial ability among depressed elders in a community setting.

Visuospatial ability is frequently compromised among elderly depressed patients, but it is unclear whether the impairment is a consequence of a visuospatial memory deficit or of an executive dysfunction that impacts visuospatial ability. The Boston Qualitative Scoring System is a method of scoring the Rey-Osterrieth Complex Figure (ROCF) that assesses the process used to draw the figure, the executive aspect of the task, as well as the accuracy and location of the completed elements. The hypotheses that executive scores as measured by the BQSS would separate diagnostic groups and that executive function would mediate the relationship between depression and nonverbal recall were tested using a between groups design with elderly depressed volunteers (N = 31) and healthy controls (N = 31). Participants were screened for other Axis I disorders with the Structured Clinical Interview for DSM-IV Diagnosis, diagnosed for major depression per DSM-IV criteria, and administered the ROCF. The copy and recall drawings were scored using BQSS criteria, and scores were grouped into executive and drawing scores from both copy and recall phases. Executive scores during the copy phase and drawing scores from the recall phase separated the diagnostic groups [F(1,59), = 4.14, P = .05] and [F(1,59) = 6.88, P = .01], respectively. Follow-up ANCOVAS showed that copy Planning, the score that quantified the process by which the figure was drawn, separated the diagnostic groups. Planning also mediated the association between depression and the percent of the figure recalled after the short delay (Z = 1.84, P < .05). The significance of the depression-to-recall pathway was eliminated when Planning was controlled for, but Planning remained related to percent recalled [B = -6.90, P < .007]. A dimension of executive dysfunction, represented here by Planning, may be one underlying source of the observed decline in nonverbal recall among elderly depressed patients. This result is consistent with the theory that dysfunction of the prefrontal cortex is a critical feature of late-life depression.

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PubMed2004

Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex.

OBJECTIVE: To examine structural abnormalities in subregions of the prefrontal cortex in elderly patients with depression, the authors explored differences in gray matter, white matter, and CSF volumes by applying a parcellation method based on magnetic resonance imaging (MRI). METHOD: Twenty-four elderly patients with major depression and 19 group-matched comparison subjects were studied with high-resolution MRI. Cortical surface extraction, tissue segmentation, and cortical parcellation methods were applied to obtain volume measures of gray matter, white matter, and CSF in seven prefrontal subregions: the anterior cingulate, gyrus rectus, orbitofrontal cortex, precentral gyrus, superior frontal cortex, middle frontal cortex, and inferior frontal cortex. RESULTS: Highly significant bilateral volume reductions in gray matter were observed in the anterior cingulate, the gyrus rectus, and the orbitofrontal cortex. Depressed patients also exhibited significant bilateral white matter volume reductions and significant CSF volume increases in the anterior cingulate and the gyrus rectus. Finally, the depressed group showed significant CSF volume reductions in the orbitofrontal cortex relative to the comparison subjects. None of the other regions examined revealed significant structural abnormalities. CONCLUSIONS: The prominent bilateral gray matter deficits in the anterior cingulate and the gyrus rectus as well as the orbitofrontal cortex may reflect disease-specific modifications of elderly depression. The differential pattern of abnormalities detected in the white matter and CSF compartments imply that distinct etiopathological mechanisms might underlie the structural cortical changes in these regions.

Aged↗
PubMed2004

Antidepressant pharmacotherapy in the treatment of depression in the very old: a randomized, placebo-controlled trial.

OBJECTIVE: This study determined the efficacy of antidepressant medication for the treatment of depression in the "old-old." METHOD: This randomized 8-week medication trial compared citalopram, 10-40 mg/day, to placebo in the treatment of patients 75 and older with unipolar depression. RESULTS: A total of 174 patients who were 58% women with a mean age of 79.6 years (SD=4.4) and a mean baseline Hamilton Depression Rating Scale score of 24.3 (SD=4.1) were randomly assigned to treatment at 15 sites. There was a main effect for site but not for treatment condition. The remission rate, defined as a final Hamilton depression scale score <10, was 35% for the citalopram and 33% for the placebo groups. However, patients with severe depression (baseline Hamilton depression scale score >24) tended to have a higher remission rate with medication than with placebo (35% versus 19%). CONCLUSIONS: In the oldest group of community-dwelling patients to be studied to date, medication was not more effective than placebo for the treatment of depression. However, given the considerable psychosocial support received by all patients, the placebo condition represents more than the ingestion of an inactive pill. Across sites, there was considerable range in response to medication, 18% to 82%, and to placebo, 16% to 80%.

Age Factors↗
PubMed2004

Localizing gray matter deficits in late-onset depression using computational cortical pattern matching methods.

OBJECTIVE: The authors used magnetic resonance imaging and an image analysis technique known as cortical pattern matching to map cortical gray matter deficits in elderly depressed patients with an illness onset after age 60 (late-onset depression). METHOD: Seventeen patients with late-onset depression (11 women and six men; mean age=75.24, SD=8.52) and 17 group-matched comparison subjects (11 women and six men; mean age=73.88, SD=7.61) were included. Detailed spatial analyses of gray matter were conducted across the entire cortex by measuring local proportions of gray matter at thousands of homologous cortical surface locations in each subject, and these patterns were matched across subjects by using elastic transformations to align sulcal topography. To visualize regional changes, statistical differences were mapped at each cortical surface location in three dimensions. RESULTS: The late-onset depression group exhibited significant gray matter deficits in the right lateral temporal cortex and the right parietal cortex, where decreases were most pronounced in sensorimotor regions. The statistical maps also showed gray matter deficits in the same regions of the left hemisphere that approached significance after permutation testing. No significant group differences were detected in frontal cortices or any other anatomical region. CONCLUSIONS: Regionally specific decreases of gray matter occur in late-onset depression, supporting the hypothesis that this subset of elderly patients with major depression presents with certain unique neuroanatomical abnormalities that may differ from patients with an earlier onset of illness.

Age of Onset↗
PubMed2003

Combined treatment with methylphenidate and citalopram for accelerated response in the elderly: an open trial.

BACKGROUND: Accelerated antidepressant treatment response may be particularly beneficial for older patients, yet there are few data to inform clinical practice. We evaluated the potential of methylphenidate to accelerate antidepressant response to citalopram and the safety and tolerability of the combined treatment in patients with geriatric major depressive disorder. METHOD: We studied 11 elderly outpatients aged 70 years and older who were diagnosed with DSM-IV major depressive disorder in a 10-week, open-label, structured trial (July 2001-July 2002). Methylphenidate was tapered and discontinued during weeks 9 and 10. Response was defined as a Hamilton Rating Scale for Depression (HAM-D) score of less than 10. The daily dose of citalopram ranged between 20 and 40 mg, and the daily dose of methylphenidate ranged between 5 and 20 mg. RESULTS: Nine patients completed the study. Six patients met criteria for accelerated response (HAM-D score < 10 and Clinical Global Impressions-Improvement scale score of 1 or 2 by treatment day 14), and 2 more patients responded by week 3. One patient was a nonresponder. The mean (SD) citalopram dose for all subjects was 27.5 (10.3) mg and the mean (SD) methylphenidate dose was 12.2 (4.9) mg. The observed side effects were mild to moderate in severity and included sedation, nausea, anxiety, polyuria, dry mouth, and hypersalivation. CONCLUSION: Methylphenidate augmentation of citalopram may be a safe and viable strategy for accelerating antidepressant response in elderly depressed patients. The results of this open-label trial need to be confirmed in a placebo-controlled trial.

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PubMed2002

MRI subcortical hyperintensities in old and very old depressed outpatients: the important role of age in late-life depression.

OBJECTIVE: There is increasing evidence that cerebrovascular factors play a key role in the etiology of late-life depression. This study examined the severity of subcortical hyperintensities (SH) and the relationship between SH and depression characteristics in two samples of elderly depressed outpatients differing in age. METHODS: The samples consisted of 59 subjects age 60 and over, (69+/-5.6 years), who participated in a trial of sertraline, and 111 subjects age 75 and over, (79+/-4.1 years), who participated in a trial of citalopram. RESULTS: The citalopram group was significantly older than the sertraline group and had more severe SH (72% vs. 42% high ratings). The High SH group was significantly older than the Low SH group in the sertraline study but there was no difference in age in the SH groups in the citalopram sample. There was no relationship between SH severity and baseline depression or age of onset. However, age strongly correlated with later age of onset. There was no relationship between SH severity and cardiovascular risk factors or treatment response in the sertraline sample. CONCLUSION: Age is a major factor for the development of SH and late-life depression. There may not be an association between SH and depression severity, cardiovascular risk factors, or treatment response in geriatric depressed outpatients. The etiologic factors and clinical course of late-life depression requires further study.

Age of Onset↗
PubMed2002

Medical burden, cerebrovascular disease, and cognitive impairment in geriatric depression: modeling the relationships with the CART analysis.

Herein, the background information reflecting roles of medical burden, cerebrovascular disease and risk factors, and cognitive impairment in geriatric depression are reviewed. The authors then propose a nonparametric statistical approach to the data analysis of multiple putative causal variables for late-life depression, the Classification and Regression Tree Analysis. This analysis presents a useful approach to modeling nonlinear relationships and interactions among variables measuring physical and mental health, as well as magnetic resonance imaging and cognitive measures in depressed elderly. This method uncovers the existing interactions among multiple predictor variables, and provide thresholds for each variable, at which its predictive power becomes statistically significant. It presents a "hierarchy" of the predictors in a form of a decision tree by finding the best combination of predictors of an outcome. The authors present two models based on demographic variables, measures of vascular and nonvascular medical burden, neuroimaging indices, the Mini-Mental State Examination score, and neuropsychological test scores of 81 elderly depressed subjects. Cognitive tests of verbal fluency and executive function are identified as the best predictors of depression, followed by the frontal lobe volume and Mini-Mental State Examination. The authors observed that an interaction between frontal lobe volume, total lesion volume, and medical burden was predictive of depression.

Journal Article↗
PubMed2002

Frontal white matter biochemical abnormalities in late-life major depression detected with proton magnetic resonance spectroscopy.

OBJECTIVE: Neuroanatomical abnormalities have been identified in patients with late-life mood disorders by using magnetic resonance imaging. This study examined the biochemical correlates of late-life major depression in the frontal gray and white matter by using single-voxel proton spectroscopy. METHOD: Twenty elderly patients with major depression and 18 comparison subjects similar in age and gender to the patients were scanned on a 1.5-T magnetic resonance scanner with head coil. Voxels were placed in the left dorsolateral white matter and bilaterally in the anterior cingulate gray matter. Absolute levels of N-acetylaspartate, choline, myo-inositol, and creatine were estimated with the LC-Model algorithm. Ratios of metabolite to creatine levels were computed from the absolute values. RESULTS: myo-Inositol/creatine and choline/creatine ratios were significantly higher in the frontal white matter in the major depression group than in the comparison group. The groups had no significant differences in the metabolite ratios in the gray matter. CONCLUSIONS: Biochemical changes in the white matter may provide some of the neurobiological substrates to late-life major depression.

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