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Biomedical subjects

I M Lesser

Publications and source records attributed to I M Lesser.

At least 19 recordsLinked to original sources
PubMed2000

Apolipoprotein-E and white-matter hyperintensities in late-life depression.

The authors conducted a follow-up study of 16 patients with late-life depression approximately 6 years after their initial assessment to evaluate the relationships between apolipoprotein-E (APO-E) status and white-matter hyperintensities (WMH). Ten patients had WMH at baseline, and four patients demonstrated an increase in WMH size over time. Three of four patients with the APO-E epsilon 4 allele demonstrated an increase in WMH over time, and only 1 of 12 patients without an epsilon 4 allele had an increase in WMH. Three of four patients with APO-E epsilon 4 allele developed a chronic course of major depression at follow-up. Patients with APO-E epsilon 4 had a higher number of depressive episodes and lower age at onset. APO-E may be a risk factor for cerebrovascular disease associated with late-life depression and may affect the clinical characteristics and disease course of depression.

Aged↗
PubMed1999

REM sleep in depression is influenced by ethnicity.

The influence of ethnicity on the manifestation of EEG sleep changes in depression was studied in 95 patients (21 African-Americans [AA], 17 Asians [AS], 37 Caucasians [C] and 20 Hispanics [H]) with unipolar major depression. Subjects were studied twice for 2 consecutive nights. On the second night of each 2-night session, placebo or scopolamine (1.5 microg/kg, IM, at 23.00 h) was administered. On the baseline (placebo) night, sleep architecture, sleep continuity and rapid eye movement (REM) sleep variables were generally comparable among the groups. However, REM sleep was less in AA and AS subjects than in C and H subjects. Furthermore, the distribution of REM sleep over the course of the night in AA and AS subjects differed significantly from that in the C and H groups. Although scopolamine significantly affected sleep continuity and REM sleep measures, no significant differential effects of scopolamine were observed. Because many antidepressants suppress REM sleep, the differences in baseline REM sleep observed might be related to the greater sensitivity of some ethnic-minority depressed patients to pharmacotherapy.

Adult↗
PubMed1999

Clinical and neuroradiologic features associated with chronicity in late-life depression.

The authors conducted a 6-year follow-up of 16 patients with late-life depression to evaluate the relationships between clinical and neuroradiologic variables and disease outcome. Patients had a comprehensive neuropsychiatric evaluation and magnetic resonance imaging (MRI) at baseline and follow-up. Eight of the 16 developed a chronic course of unremitting major depression sufficient to cause significant psychosocial impairment. Six patients with a chronic course and four patients with a non-chronic course of depression had white matter hyperintensities (WMH) on MRI at baseline. Four patients whose WMH increased in size over time developed a chronic unremitting course of depression. No patients with non-chronic depression had large areas of WMH at baseline or exhibited increased WMH size over time. Chronic depression was associated with severity of cerebrovascular risk factors, apathy, and poor quality of life. Treatment and prevention of cerebrovascular disease may improve the outcome of late-life depression.

Adult↗
PubMed1998

Base rates of "impaired" neuropsychological test performance among healthy older adults.

Base rates of deficient neuropsychological test performance were evaluated among 132 neurologically healthy older normal adults using a variety of measures commonly employed in the "flexible-battery"approach to neuropsychological assessment. Subjects were divided into three age groups (50 to 59, 60 to 69, and 70 to 79 years). Despite the healthy status of our sample, most tests yielded at least some proportion of subjects earning scores in the borderline and impaired ranges (1.3 and 2.0 standard deviations below the age-group mean, respectively). Across the battery of measures, 73% of subjects earned a borderline score on at least one measure, and 20% of subjects earned at least two scores in the impaired range on separate tests. The proportion of subjects consistently earning borderline or impaired scores across multiple measures within specific cognitive domains was generally lower. Results illustrate the problems in interpreting isolated low scores, and the need to consider false-positive base rates in drawing inferences from poor test performance.

Journal Article↗
PubMed1998

Relationship of age, age at onset, and sex to depression in older adults.

The authors investigated the relationships among factors of age, age at onset, and sex in depressed older adults. A group of 96 outpatients (mean age, 60) diagnosed with late-(LOD) and early-onset (EOD) major depression were assessed for severity of depression and underwent magnetic resonance imaging (MRI). The MRI scans were rated for severity of white-matter hyperintensities (WMH) and ventricle-to-brain ratio (VBR). LOD was associated with increased amounts of WMH, larger VBR, and history of hypertension. Men were more severely depressed than women, with higher rates of neurovegetative signs and history of smoking. Age correlated with increased VBR and WMH, history of hypertension, history of percipitants for the current episode, and lack of social support. Results suggest that a subgroup of men may be more at risk for LOD associated with WMH and that sex and age at onset need to be considered in future studies.

Age Factors↗
PubMed1997

Differential response of rapid eye movement sleep to cholinergic blockade by scopolamine in currently depressed, remitted, and normal control subjects.

The degree of cholinergic dysregulation of sleep in adult depression was evaluated using scopolamine. On separate sessions, placebo and scopolamine (4.5 micrograms/kg, IM) were administered to 14 patients with unipolar major depression, 16 recovered/remitted patients, and 18 normal controls. Scopolamine increased rapid eye movement (REM) latency (RL), reduced REM activity (RA), REM density (RD), and REM duration, and increased the percentage of stage 4 sleep in all groups. There was a differential effect of scopolamine on RL, RA, and REM duration for the first REM period, and on percentage of stage 4 sleep. Whereas a primary cholinergic hyperactivity could account for the RA and RD responses, the response profile for RL was more compatible with reduced aminergic tone as the proximal cause of the cholinergic hyperactivity. Whether the sleep abnormalities observed in remitted patients reflect an underlying vulnerability for development or recurrence of depression, and/or a scar, remains to be determined.

Adult↗
PubMed1997

Behavioral phenomenology in Alzheimer's disease, frontotemporal dementia, and late-life depression: a retrospective analysis.

Often patients in the early stages of Alzheimer's disease (AD), frontotemporal dementia (FTD), and late-life depression can be difficult to differentiate clinically. Although subtle cognitive distinctions exist between these disorders, noncognitive behavioral phenomenology may provide additional discriminating power. In 19 subjects with AD, 19 with FTD, 16 with late-life psychotic depression (LLPD), and 19 with late-life nonpsychotic depression (LLNPD), noncognitive behavioral symptoms were quantified retrospectively using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and compared using both a one-way ANOVA and a multivariate stepwise discriminant analysis, which utilized a jackknife procedure. The FTD group showed the highest mean total SCAN score, while the AD group showed the lowest. ANOVA showed significant differences in the mean total SCAN scores between the four diagnostic groups (P < .0001). With the discriminant analysis, the four disorders demonstrated different clusters of behavioral abnormalities and were differentiated by these symptoms (P < .0001). A subset of 14 SCAN item group symptoms was identified that collectively classified the following percentages of subjects in each diagnostic category: AD 94.7%, FTD 100%, LLPD 87.5%, and LLNPD 100%. These results indicate that AD, FTD, LLPD, and LLNPD were distinguished retrospectively by the SCAN without using cognitive data. Better definition of the longitudinal course of noncognitive behavioral symptoms in different dementias and psychiatric disorders will be valuable both for diagnosis and to help define behavioral syndromes that are associated with selective neuroanatomic and neurochemical brain pathology.

Aged↗
PubMed1997

Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors.

BACKGROUND: Patients with frontotemporal dementia (FTD) present initially with primarily behavioral rather than cognitive symptoms. Decreased serotonin receptor binding has been reported in the frontal lobes, temporal lobes, and hypothalamus in autopsy-proven FTD cases. This study tests the hypothesis that many of the behavioral symptoms of FTD (including disinhibition, depressive symptoms, carbohydrate craving, and compulsions) will respond to serotonin selective reuptake inhibitors (SSRIs). METHOD: Eleven subjects meeting the Lund-Manchester clinical, neuropsychological, and neuroimaging criteria for FTD were treated with SSRIs (fluoxetine, sertraline, or paroxetine). After 3 months, treatment responses for disinhibition, depressive symptoms, carbohydrate craving, and compulsions were evaluated prospectively without placebo control. RESULTS: After treatment, disinhibition, depressive symptoms, carbohydrate craving, and compulsions all showed improvement in at least half the subjects in which they had been present. One subject stopped sertraline treatment because of diarrhea, while another stopped paroxetine treatment due to increased anxiety. The presence of individual behavioral symptoms and also the response of each symptom to SSRIs were unrelated to cognitive impairment as measured by baseline Mini-Mental Status Examination (.07 < or = p < or = 1.00) [corrected]. CONCLUSION: The behavioral symptoms of FTD may improve after treatment with SSRIs. Future neurochemical studies and controlled pharmacologic trials may improve available treatments.

1-Naphthylamine↗
PubMed1996

Neuropsychological deficits among older depressed patients with predominantly psychological or vegetative symptoms.

Depressed outpatients having primarily psychological or vegetative symptoms, as defined by the factor analytically developed Hamilton Depression Scale superfactors described by Rhoades and Overall (1983), were compared with similarly aged normal controls on a comprehensive neuropsychological battery. The vegetative group evidenced poorer performance than controls on several measures associated with right hemisphere functioning and on a task associated with executive functioning. In contrast, the psychological group did not significantly differ from controls on any measure, and had significantly better performance than the vegetative group on several tasks. These findings suggest that neuropsychological deficits associated with depression may be limited to those patients with primarily vegetative symptoms.

Aged↗
PubMed1996

Cognition and white matter hyperintensities in older depressed patients.

OBJECTIVE: The authors compared amounts of white matter hyperintensity in late- and early-onset depressed patients and never-depressed older subjects, compared neuropsychological function in these groups, and investigated the association between white matter hyperintensities and cognitive function in depression. METHOD: Sixty currently depressed patients whose first depression occurred after age 50 years, 35 depressed patients over age 50 whose first depression occurred before age 35, and 165 nonpsychiatrically ill subjects over age 50 underwent magnetic resonance imaging (MRI) and neuropsychological evaluation. Areas of white matter hyperintensity were measured from MRI images. RESULTS: The late-onset patients had more white matter hyperintensity than either of the other groups. Compared to the nondepressed subjects, the patients had significantly lower scores in the cognitive domains of nonverbal intelligence, nonverbal memory, constructional ability, executive ability, and information processing speed. The cognitive abnormalities were mostly confined to the late-onset patients, and the presence of a large amount of white matter hyperintensity was associated with significantly poorer executive skills. However, most of the scores were not in the significantly impaired range. CONCLUSIONS: Large amounts of white matter hyperintensity are more frequent in patients with late-onsetdepression than in elderly subjects with early-onset or no depression. Both late- and early-onset elderly depressed patients show mild decrements in some "right hemisphere" cognitive skills; the late-onset subjects also show deterioration in information processing speed and executive functions. Patients with large amounts of white matter hyperintensity have significantly poorer executive function.

Age Factors↗
PubMed1996

The evolving science of pharmacogenetics: clinical and ethnic perspectives.

The field of pharmacogenetics has witnessed remarkable progress during the past several decades. Clinical observations of severe toxic reactions and findings of dramatic interindividual as well as cross-ethnic differences in response to therapeutic agents have been instrumental in fostering advances of the field. Research on cytochrome P450 isozymes may be of particular importance to the field of psychiatry, because most psychotropics depend on these enzymes for their biotransformation. This article traces the progress of research in this area and highlights the importance of clinical and cross-ethnic observations in providing the impetus and direction for the field. Knowledge derived from this line of research is likely to make important contributions toward establishment of rational guidelines for psychopharmacotherapy. In addition, research on these enzymes may also have profound implications in regard to the pathogenesis of a number of major disorders, including several types of commonly encountered cancers, as well as neuropsychiatric problems, including Parkinson's disease, tardive dyskinesia, addiction, and drug-induced neurotoxicity.

Cytochrome P-450 Enzyme System↗
PubMed1996

Brain imaging, antidepressants, and ethnicity: preliminary observations.

Magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) using 99mTc-hexamethylpropylene amine oxime (HMPAO) evaluations were completed on African-American and Caucasian depressed patients prior to their participation in an antidepressant medication trial. The degree of white matter hyperintensities (WMH), ventricle-to-brain ratio (VBR), and uptake of HMPAO did not vary significantly between the groups. After 1 week of placebo run-in, patients received paroxetine in an 8-week, open-label, flexible-dose trial. Final dosages and side effects were similar between groups. There was a trend for the Caucasian patients to have a better treatment response, but the relatively small sample size makes this finding tentative. In general, there were no major differences in either baseline neuroimaging findings or response to paroxetine between these two ethnic groups.

Black or African American↗
PubMed1994

Reduction of cerebral blood flow in older depressed patients.

BACKGROUND: We investigated regional cerebral blood flow in older, drug-free depressed patients and examined factors that might be related to rCBF. METHODS: We studied 39 physically healthy depressed patients over the age of 50 years and 20 psychiatrically healthy control subjects. Regional cerebral blood flow was measured with single photon emission computed tomography, using both xenon 133 (to quantify regional cerebral blood flow) and 99mTc-hexamethylpropylene amine oxime (to make regional comparisons). From magnetic resonance imaging, we derived a semiquantitative measure of areas of white matter hyperintensity and a ventricle-to-brain ratio. RESULTS: Patients exhibited a global reduction in regional cerebral blood flow compared with controls, with the orbital frontal and inferior temporal areas affected bilaterally. Regional cerebral blood flow was also reduced in higher brain slices in the right but not the left hemisphere. Significant predictors of lowered regional cerebral blood flow were being depressed, being male, and having a greater ventricle-to-brain ratio. There appeared to be a subgroup of patients who demonstrated large areas of white matter hyperintensity and low regional cerebral blood flow. CONCLUSIONS: Cerebral blood flow was lower in older, medication-free depressed patients than in age-matched control subjects, involved the orbital frontal and anterior temporal regions, and was more reduced in the right hemisphere.

Age Factors↗
PubMed1993

Wisconsin Card Sorting Test performance in healthy, older adults: relationship to age, sex, education, and IQ.

We obtained Wisconsin Card Sorting Test (WCST) scores on 91 (35 male and 56 female) healthy, well-educated individuals aged 45 to 83. Women scored better than men on six WCST scores (categories, errors, perseverative responses, % perseverative errors, % conceptual level responses, and trials to first category), while subjects with more than 16 years of education outscored those limited to high school education on four measures (perseverative responses, errors, % perseverative errors, % conceptual level responses). Individuals older than 70 years of age scored less well than younger subjects on only two indices (errors, % conceptual level responses). Full Scale IQ was not related to WCST scores. Our findings suggest that WCST scores should be interpreted within the context of patient gender, education, and age.

Age Factors↗
PubMed1993

Brain imaging in late-life schizophrenia and related psychoses.

Despite disagreements about nomenclature, patients who develop schizophrenic or schizophrenia-like symptoms in later life are often seen in clinical practice. Questions about the etiology of late-life psychotic disorders and about their similarities or differences from early-onset disorders remain unanswered. Neuro-imaging techniques have been used to study patients with late onset of psychosis, and in substantial subgroups of patients (from 25% to 100% in various studies) compared with age-matched control subjects, structural and functional abnormalities have been found. We review the literature on imaging in late-life schizophrenia and related psychotic disorders, and we present data from our own investigations of patients with these disorders. We discuss the potential usefulness of imaging evaluations in patients with late-onset disorders, and we offer suggestions for future investigations.

Aged↗
PubMed1992

Neuropsychological correlates of white-matter lesions in healthy elderly subjects. A threshold effect.

The clinical significance of white-matter lesions (WMLs) detected by computed tomography and magnetic resonance imaging in healthy elderly subjects has been controversial, with some studies reporting associated deficits in cognition and others failing to document cognitive disturbance. In our sample of 100 healthy elderly individuals, almost half (n = 46) had no WMLs, approximately one fourth had minimal (less than or equal to 1 cm2; n = 27) or moderate (greater than 1 cm2 but less than or equal to 10 cm2; n = 21) WML areas, and six subjects had large WML areas (greater than 10 cm2). Substantial disturbances in basic attention and selected frontal lobe skills were detected in the six subjects with the large WML areas. These findings suggest that a "threshold" of WML area must be present before cognitive deficits are observed. Surprisingly, no significant relationships between duration of hypertension or cholesterol levels and WMLs were detected, suggesting that factors other than vascular disturbances are involved in the origin of at least some WMLs.

Aged↗