Venous thrombectomy for iliofemoral vein thrombosis--10-year results of a prospective randomised study

In a longitudinal evaluation of 37 patients with severe depression who had undergone brain magnetic resonance imaging (MRI) 6 months-2 years (mean 14.1 months) previously, the degree of residual dysfunction was predicted by the extent of subcortical white matter hyperintensities (WMHS, p < .01), longer time elapsed since the MRI scan (p < .05), older age (p < .05), and older age at onset of affective disorder (p < .05). Ten (27%) patients developed "probable" dementia syndromes of the vascular type, with such syndromes being predicted by WMHS (p < .01) and older age of onset of affective disorder (p < .05). Institutionalization of patients was predicted largely by the combination of chronic depression, progressive cognitive decline, and advanced age. The study supports the notion that a subgroup of patients with late-onset depressive disorders, without a family history of depression, and with risk factors to cerebrovascular disease, have extensive WMHS on MRI, and that such structural brain changes predispose to chronic depression and progressive cognitive decline.     

Endothelin: role in hypertension

Thirty-nine elderly depressed patients as well as 15 demented patients with Alzheimer's disease and 11 healthy volunteers were imaged at rest with a high resolution single-slice 12-detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-Exametazime (HM-PAO). Statistical parametric maps were computed to compare early- and late-onset depressed, Alzheimer patients and healthy volunteers and to examine associations between regional perfusion and clinical and MRI variables. Patients with late-onset depression showed reductions in temporal lobe perfusion compared with early-onset depression and controls. Alzheimer patients had the expected reduced perfusion in temporoparietal and prefontal cortex, as well as basal ganglia, compared with healthy controls. Compared with depressed patients, they showed a relative reduction in temporoparietal cortex, only. This difference was more pronounced between Alzheimer patients and early onset, compared to late-onset patients with depression. Periventricular white matter changes on MRI were associated with temporal lobe reductions of tracer uptake in depression. In the Alzheimer group, deep white matter MRI changes were associated with frontal perfusion deficits. Our results support a vulnerability hypothesis, which predicts that patients with late-onset depression will show more brain changes than patients with an early onset of their illness. Statistical parametric mapping in patients with organic psychiatric brain syndromes is feasible and promising as a clinical and research method.     

MRI signal hyperintensities in geriatric depression

OBJECTIVE: The authors rated periventricular and subcortical signal hyperintensities on magnetic resonance imaging (MRI) scans in elderly patients with depression and in normal subjects with similar demographic features to examine whether such changes discriminate patients with depression from normal subjects and whether they are associated with any clinical variables. METHOD: Two established hyperintensity rating systems were used to compare the MRI brain scans of 48 elderly patients with depression diagnosed according to DSM-III-R with the scans of 39 normal elderly subjects. RESULTS: Elderly depressed patients manifested significantly more severe hyperintensity ratings in the subcortical gray matter than age-matched comparison subjects. Significant differences were not identified between patients with similar current ages and cerebrovascular disease risk who had early-onset or late-onset depression. CONCLUSIONS: These findings support those of neuroimaging studies implicating the basal ganglia in depression and geriatric depression. The data suggest that the relationship observed in some reports between late-onset depression and MRI hyperintensities is most likely a function of cerebrovascular disease risk and age.     

Hippocampal sclerosis contributes to dementia in the elderly

OBJECTIVE: To assess the relevance of hippocampal sclerosis (HS) to dementia in the elderly. BACKGROUND: HS is a prominent pathologic finding in some demented elderly, but the anatomic substrate and cognitive profiles of this dementia have not been well established. DESIGN/METHODS: An autopsy series, including dot-immunobinding assay to estimate neocortical synaptic density, of eight patients (three men, five women) with HS on whom extensive antemortem neuropsychological testing was available. RESULTS: Mean age at onset was 72.0 (+/-9.8) (range, 59 to 89) with a mean duration of symptoms of 6.5 (+/-2.9) years. Patients were only mildly impaired with a mean MMSE of 20.9 (+/-4.9) and a mean DRS of 103.1 (+/-12.5) at presentation. Cardiovascular disease was present in 88%, with a mean Hachinski score of 3.4 (+/-2.2). No patient had a history of seizures. Sixty-three percent had depression or depressive symptoms. Neuropsychologically, most patients presented with prominent memory and language deficits and became progressively demented. Neuropathologically, isolated HS was a rare finding; many patients had either very mild or neocortical "plaque only or plaque predominant" Alzheimer's disease (AD) in addition to HS changes. Midfrontal neocortical synaptophysin counts were significantly reduced in all HS patients compared with controls (p = 0.0006). CONCLUSIONS: In the elderly, HS can be a neuropathologic substrate of dementia. Clinically, it can be associated with a course that is difficult to distinguish from AD although cardiac disease and depression are frequent concomitants. Deterioration of cognitive function in these subjects may relate to other pathologic features such as neocortical synapse loss.     

Greater abnormalities of brain cerebrospinal fluid volumes in younger than in older patients with Alzheimer's disease

OBJECTIVE: This study used a semiautomated analysis technique to quantify differences in regional brain cerebrospinal fluid volumes observed with computed tomography between healthy adults and patients with Alzheimer's disease (AD). DESIGN: Cross-sectional, between-subject design, using an age-regression model. SETTING: Palo Alto (Calif) Department of Veterans Affairs Medical Center. PATIENTS AND OTHER PARTICIPANTS: The 117 patients with probable or definite AD were recruited from the Geriatric Psychiatry Research Unit and National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 114 healthy volunteers were recruited from the local community. MAIN OUTCOME MEASURES: Cerebrospinal fluid volumes estimated from computed tomographic scans and neuropsychological test scores. RESULTS: The computed tomographic estimates of ventricular and sulcal cerebrospinal fluid volumes increased significantly in all sampled brain regions in normal aging and were vastly larger in AD than in normal aging. Furthermore, younger patients with AD had significantly greater cerebrospinal fluid volume enlargement than did older patients with AD compared with healthy controls of their age. When the AD group was divided on the basis of reported age at symptom onset, patients in the early-onset group (onset before age 65 years) were quantitatively more abnormal than and showed a different pattern of abnormality from the patients in the late-onset group. This onset difference was also evident in neuropsychological test performance. CONCLUSIONS: This cross-sectional study revealed a number of converging findings that suggested greater abnormality in the early-onset than in the late-onset group of patients with AD. The possibility remains, however, that the two onset groups represent different stages along a continuum of pathologic changes.     

The effect of gender and age at onset of depression on mortality

BACKGROUND: Depression has a marked negative impact on geriatric patient mortality and morbidity. The risk factors and exact reasons for these effects are not well understood. METHOD: Seeking to better define the factors, we retrospectively analyzed the effects of gender and age at onset of affective disorder in a naturalistic study of 192 geriatric patients consecutively admitted to a large midwestern tertiary care center between 1980 and 1987 for the treatment of unipolar depression. RESULTS: After controlling for age at index admission, patients with an onset of depression before age 40 suffered significantly (p < .05) less mortality in follow-up than those with onset after age 40. When effects of gender are examined, the effects of age at onset are most profound in women, with a threefold increase in the rate of death in the cohort with age at onset of depression after 70 years when compared to those with onset before age 40. CONCLUSION: These results and those of others suggest that depressed elderly women with no previous history of affective disorder are at a markedly increased risk compared with elderly women with a history of affective illness for morbidity and mortality and that a significant proportion of elderly depressed patients are admitted to a psychiatric hospital for a depression that is secondary to serious medical illness.     

Increased rate of psychosis and psychomotor change in depression with age

BACKGROUND: We examined the phenomenology of depression in younger (< 60 years old) versus older (> or = 60 years) subjects and, more specifically, the interaction between age and psychomotor disturbance associated with depression. METHOD: Two hundred and eighty-five patients with a DSM-III-R diagnosis of unipolar major depression referred to a mood disorders unit were assessed using the CORE rating scale, a sign-based system for defining melancholia. Subjects were also assessed using the Hamilton Rating Scale for Depression, Zung Depression Scale, Newcastle Endogenous Depression Inventory and the General Health Questionnaire. RESULTS: The total CORE score (and each of its subscales) was found to interact with age. Rates of psychotic and melancholic depression increased with age. Elderly depressives suffered more severe depression (higher HRSD scores), appetite loss and weight loss. Level of psychomotor disturbance and rates of psychosis did not differ between those elderly subjects with an early onset (before the age of 60 years) and those with a late onset (at or after 60 years) of depression. CONCLUSIONS: There appear to be robust phenomenological differences in depression between older and younger subjects. The association between age and psychomotor change may assist our understanding of the neurobiology of depression.     

Impairment of the semantic network in schizophrenia

It is well established that patients with schizophrenia display a variety of language impairments. Despite considerable research, however, the underlying mechanisms of the language deficits in schizophrenia remain unclear. Representations of semantic networks of 56 patients with schizophrenia and 28 normal comparison (NC) subjects of similar ages and educational levels were generated by multidimensional scaling and Pathfinder analyses of their responses on the Animal Fluency Test. On the basis of traditional scoring techniques (i.e., total number of correct animal names generated in 60 s), all patients performed significantly worse than the NC subjects. More detailed analyses of the underlying semantic networks revealed that performance in the patients varied according to age of onset and subtype of schizophrenia. The semantic network of patients with late-onset schizophrenia (i.e., with onset after age 45) was virtually identical to that of the NC group. In contrast, the semantic network of patients with a younger age of onset was disorganized and differed significantly from that of the NC subjects. Findings demonstrated that patients with nonparanoid subtypes displayed greater disorganization in their semantic networks than patients with a paranoid subtype. Although general fluency impairments (e.g., difficulties in initiation, retrieval, and search mechanisms) may be sensitive to schizophrenia, per se, specific deficits in the structure of semantic knowledge may be associated with certain characteristics of individual patients with schizophrenia, such as an earlier age of onset and nonparanoid subtype.     

Multilobar polymicrogyria, intractable drop attack seizures, and sleep-related electrical status epilepticus

BACKGROUND AND OBJECTIVE: Patients with cortical malformations often have intractable seizures and are candidates for epilepsy surgery. Within an unselected series of patients with various forms of cortical malformation, nine patients with multilobar polymicrogyria had electrical status epilepticus during sleep (ESES) accompanied by infrequent focal motor seizures. Eight patients also had intractable atonic drop attack seizures. Because ESES usually is accompanied by a good long-term seizure prognosis, the objective of this study was to examine ESES outcome among patients with a structural lesion that is usually highly epileptogenic and has a low seizure remission trend. METHODS: The nine patients had follow-up periods lasting 4 to 19 years. All underwent brain MRI, serial sleep EEG recordings, and cognitive testing during and after ESES. RESULTS: ESES and drop attack seizures appeared between the ages of 2 and 5 years (mean, 4 years) and ceased between the ages of 5 and 12 years (mean, 8 years). At the last visit patients were 8 to 23 years of age (mean, 14.5 years) and were either seizure free or had very infrequent focal motor seizures during sleep. Three patients were free from antiepileptic drugs. In no patient was definite cognitive deterioration apparent after ESES in comparison with earlier evaluations. CONCLUSIONS: Age-related secondary bilateral synchrony underlying ESES may be facilitated in multilobar polymicrogyria. The good seizure outcome contrasts with that usually found in the presence of cortical malformations. For children with polymicrogyria and drop attack seizures, surgical treatment of the epilepsy should be considered cautiously, and sleep EEG recordings should be performed systematically.     

Disability in geriatric depression

OBJECTIVE: The authors' purpose was to identify the relationship of disability to clinical measures that are part of a comprehensive psychiatric examination of depressed elderly patients. METHOD: The disability of 75 elderly inpatients and outpatients with major depression whose cognitive function ranged from normality to mild dementia was assessed with the Philadelphia Multilevel Assessment Instrument. Age at onset of depression, chronicity of depression, severity of depression, cognitive impairment, medical burden, social support and living environment were assessed with standardized instruments. RESULTS: Impairment in instrumental activities of daily living was significantly associated with advanced age, severity of depression, and medical burden. The relationship of depressive symptoms to impairment in instrumental activities of daily living was not influenced by age or medical burden. Anxiety and depressive ideation as well as retardation and weight loss were significantly associated with impairment in instrumental activities of daily living. Interviewer-rated global disability was associated with advanced age at onset of depression, medical burden, and overall cognitive impairment. Specifically, a disturbance in initiation and perseveration was significantly related to global disability. CONCLUSIONS: Impairment in instrumental activities of daily living appears to be a relatively independent dimension of health status that is related to depressive symptoms, particularly anxiety and depressive ideation as well as retardation and weight loss. Global disability may be associated with impairment in initiation and perseveration and with late onset of depression. These findings provide a basis for studies investigating whether psychotherapy aimed at depressive ideation and rehabilitation efforts focused on instrumental activities of daily living can improve the outcome of geriatric depression.     

Electroclinical and neuroimaging studies in epilepsy

INTRODUCTION AND MATERIAL: During 54 months, we have studied the electro-clinical and neuroimaging features in outpatients with active epilepsy. Each patient was interviewed for one of us. Then, we have reviewed the medical records about both the clinical featuring. EEG and neuroimaging (NI) studies and seizures frequency (SF) outcome. Differences in crude proportions were assessed by chi 2 test for independence by 2 x 2 tables. RESULTS AND CONCLUSIONS: It has been 207 patients with 49 +/- 19.6 years of mean age at review. Partial seizures was significantly related with both a higher SF at onset and politherapy. Also, with a focal EEG distribution but only in case of complex partial seizures. Abnormal NI was significantly more frequent in oldest patients. A greater proportion of patients were in politherapy in four situation: SF at onset > 1 by day, a focal EEG distribution, duration of epilepsy longer than 20 years and age of onset lesser than 60 years. A 37.2% was seizures-free in the last year and in 34% the SF was improved a 50% or more from the beginning. A significantly greater proportion of patients was following with seizures in four cases: when the SF at onset has been > or = 1 by day, being partial seizures, women and having politherapy.     

Age at onset and language disturbances in Alzheimer's disease

This study examined the effect of age at symptom onset of Alzheimer's disease (AD) on the pattern of language disturbance. We assessed 150 consecutive patients with a clinical diagnosis of mild-to-moderate AD using the Western Aphasia Battery and a 100-item picture-naming test. A multivariate linear regression analysis examined the effect of age at onset after controlling for gender, education, severity of dementia and duration of the disease. Patients with early onset performed significantly worse than did patients with late onset on the word comprehension and sequential commands subtests. On the other hand, late-onset patients performed more poorly than early-onset patients on the picture-naming test in a subgroup with mild language deficits. However, the trend disappeared in other subgroups with more degraded language function. We consider that the concomitant effects of normal aging worsened the picture-naming deficits in the late-onset patients, and the rapid decline of naming ability in the early-onset patients masked the aging effect with the progression of language deficits. The deterioration of word comprehension and the rapid decline of naming ability are the characteristics of early-onset patients. The different patterns of language deficits between early- and late-onset patients may correspond to the genetic heterogeneity of AD.     

Catalytic properties of the purified rat hepatic cytosolic cholesteryl ester hydrolase

Alzheimer's disease (AD) is a heterogeneous entity presenting as sporadic and familial disease. In familial AD, there is evidence for genetic linkage to a yet undefined gene on chromosome 14 in early-onset pedigrees and on chromosome 19 in late-onset pedigrees. In a few early-onset kindreds, there were mutations in the amyloid precursor gene on chromosome 21. There is an increased frequency of apolipoprotein E (ApoE) epsilon4 allele in patients with late-onset AD. We studied the clinical presentation and profile of cognitive deficits in 58 AD patients at the early stage of the disease. We divided the AD patients into subgroups of sporadic late-onset (SLO) (> or = 65 years), familial late-onset (FLO) (> or = 65 years), sporadic early-onset (SEO) (<65 years), and familial early-onset (FEO) (<65 years) patients and into three subgroups according to their ApoE genotype zero epsilon4, one epsilon4, and two epsilon4 alleles. The AD subgroups did not differ in the global clinical severity of dementia or the duration of the disease. SLO, FLO, SEO, and FEO subgroups did not differ in clinical characteristics such as occurrence of rigidity, hypokinesia, tremor, myoclonus, hallucinations, delusions, or epileptic seizures nor in the profile of deficits on tests assessing memory, language, visuospatial, executive, and praxic functions. The epsilon4++ allele frequency was 0.43 for all AD patients and did not differ across subgroups divided according to the familial aggregation and age of onset. Patients with two epsilon4 alleles had earlier age at onset of dementia than those with no epsilon4 allele (63 +/- 9 versus 68 +/- 9 years), but otherwise the clinical symptoms and signs were not related to the ApoE genotype. However, the AD patients with two epsilon 4 alleles had lowest scores on memory tests and differed significantly from those with one or zero epsilon4 allele in the delayed list learning (p<0.05) and from those with zero epsilon4 allele in the immediate and delayed story recall. In contrast, verbal functions were better preserved in two epsilon4 patients than in those with other ApoE genotypes. This study failed to confirm the earlier reports of severe aphasia, agnosia, and apraxia in familial AD patients, but the clinical phenotype was similar irrespective to the familial aggregation. However, AD patients with two epsilon4 alleles are characterized by more severe memory loss and earlier age of onset than those without the epsilon4 allele.     

Youth depression and early childrearing: Stress generation and intergenerational transmission of depression.

Objective: Broadening the concept of stress generation beyond acute life events, the current study explores predictors of the creation of stressful environments—specifically, selection into early childrearing by age 20. It was predicted that youth with early onset depressive disorders would be at higher risk for early childrearing accompanied by greater depression and parenting maladjustment. Additional analyses tested hypotheses about the roles of interpersonal vulnerability and intergenerational transmission of depression and examined gender differences. Method: A community sample of 706 adolescents and their mothers were studied at ages 15 and 20. The sample was originally selected to oversample families with depressed mothers. Results: Results confirmed the hypotheses for women but not men: Young women with depression by age 15 were at greater risk for interpersonal difficulties at age 15 and early childrearing, accompanied by further depression and parenting dysfunction at age 20. The effects of (grand)maternal depression were evident in predicting youth early onset depression and interpersonal difficulties, as well as higher rates of depression among their daughters who had children by age 20. Conclusions: The study expands the definition of stress generation to include the role of past depression and other risk factors as predictors of selection into a stressful childrearing environment. The findings also describe aspects of the intergenerational transmission of depression. The results highlight potentially important targets for interventions in young women to prevent recurrence of major depression and parenting dysfunction. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Prevalence of anxiety disorders and their comorbidity with mood and addictive disorders

BACKGROUND: The co-occurrence of anxiety disorders with other mental, addictive, and physical disorders has important implications for treatment and for prediction of clinical course and associated morbidity. METHOD: Cross-sectional and prospective data on 20,291 individuals from the Epidemiologic Catchment Area (ECA) study were analysed to determine one-month, current disorders, one-year incidence, and one-year and lifetime prevalence of anxiety, mood, and addictive disorders, and to identify the onset and offset of disorders within the one-year prospective period. RESULTS: Nearly half (47.2%) of those meeting lifetime criteria for major depression also have met criteria for a comorbid anxiety disorder. The average age of onset of any lifetime anxiety disorder (16.4 years) and social phobia (11.6 years) among those with major depression was much younger than the onset age for major depression (23.2 years) and panic disorder. CONCLUSIONS: Anxiety disorders, especially social and simple phobias, appear to have an early onset in adolescence with potentially severe consequences, predisposing those affected to greater vulnerability to major depression and addictive disorders.     

Obituary: Arthur Mourant (1904-1994)

Twenty patients with HIV infection and mania were grouped according to whether their first manic episode occurred when CD4 count was < 200 (late onset) or > or = 200 (early onset). The late-onset patients were less likely to have personal or family histories of mood disorder and more likely to have dementia or cognitive slowing. They also exhibited a different manic symptom profile. The different sociodemographic and symptom profiles associated with early-onset and late-onset mania may reflect differences in pathophysiology.     

The differences in electroencephalographic changes in patients undergoing carotid endarterectomies while under local versus general anesthesia

OBJECTIVE: This study compared the electroencephalographic (EEG) changes occurring during carotid occlusion in 225 consecutive patients undergoing carotid endarterectomies performed by two surgeons, one using local and the other using general anesthesia. METHODS: A retrospective review of patients undergoing carotid endarterectomies for carotid occlusive disease was conducted. EEG changes associated with intraoperative ischemia (decreased amplitude, generalized slowing, and loss of fast activity) resulting in the need for an indwelling arterial shunt were recorded for the two anesthesia groups. To determine the similarities or differences between the two groups, the groups were compared regarding age, risk factors, and indications for surgery. RESULTS: Significant EEG changes were noted in 6 of 96 patients (6.3%) in the local anesthesia group versus 19 of 121 patients (15.7%) in the general anesthesia group. EEG changes consisted solely of generalized slowing in the local anesthesia group, whereas a more varied spectrum was observed in the general anesthesia group. The two groups were similar regarding age and risk factors. Although the local anesthesia group had more asymptomatic patients, symptomatic patients did not have a greater incidence of EEG changes. CONCLUSION: There is a large difference in EEG changes potentially requiring shunt placement in patients undergoing surgery while under local (6.3%) versus general (15.7%) anesthesia. This could not be explained based on age, risk factors, interpretation of EEG findings, or indications between the two groups. We conclude that EEG monitoring may be insensitive and may fail to detect ischemia in patients who are under regional anesthesia. Alternately, the presence of general anesthetics may alter the character of the EEG findings and increase the sensitivity of EEG monitoring to ischemic events.     

Aneuploidy index in blood: a potential marker for early onset, androgen response, and metastasis in human prostate cancer

OBJECTIVES: To investigate whether the frequency of chromosome abnormalities in peripheral blood lymphocytes defined as the aneuploidy index in blood (AnIB) can be used as a clinical marker of early age onset, androgen response, and metastasis in human prostate cancer. METHODS: Peripheral blood samples were collected from 80 patients with prostate cancer, and chromosome preparations were made from 72-hour cultures after mitotic block. The AnIB of 59 informative cases was compared with several parameters, including age at disease onset, Gleason grade of tumor, clinical stage of tumor, metastasis, and prostate-specific antigen (PSA) level. RESULTS: Patients with AnIB levels greater than 3 had a significantly higher incidence of metastasis (P = 0.022), androgen-independent disease (P = 0.002), and early age at disease onset (age at diagnosis less than 65 years) (P = 0.002) compared with the patients with lower AnIB (less than 3) levels. In addition, patients with AnIB levels greater than 5 had higher PSA levels (greater than 20 ng/mL) (P = 0.029) than patients with AnIB levels less than 5. CONCLUSIONS: Chromosome abnormalities can be detected in the peripheral lymphocytes of patients with prostate cancer, and AnIB can be used as an early diagnostic and predictive marker for prostate cancer metastasis and androgen-independent disease.     

Alzheimer-type lesions in Huntington's disease

Cognitive changes in Huntington's disease (HD) are variously related to diffuse cortical atrophy with neuron loss and dystrophic neurites leading to disruption of striato-frontal or limbic circuitries, while recent studies suggest an increasing prevalence of Alzheimer-like lesions in HD brain. A comparative morphological study of 27 autopsy cases of HD (age 34 to 75 years) and of 26 age- and sex-matched non-demented controls was performed. Absence of Alzheimer-type lesions was seen in 33% of HD brains (mean age 49 years); 48% showed early non-neuritic tau pathology in limbic areas (Braak stages I and II) without amyloid deposits occurring as early as age 34 years (mean age 54 years), while Braak stages II and III with amyloid plaques were present in 19%, the youngest such HD patient being 42 years (mean age 54 years). In controls, similar tau pathology changes with later onset (age 45 years) and occurrence of amyloid plaques in 26%--all aged over 60 years--were observed. No probable or definite cases of Alzheimer disease (AD) according to CERAD criteria were seen in both cohorts. Those data confirm previous studies on the rare coexistence of HD and AD, although initial stages of Alzheimer-like lesions develop rather early in HD patients, but obviously show less rapid progress even in advanced age. The reasons for the early onset but mild progress of Alzheimer-like lesions in HD and their contribution to cognitive decline await further elucidation.