Reduction of cognitive and motor deficits after traumatic brain injury in mice deficient in poly(ADP-ribose) polymerase.
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Poly(ADP-ribose) polymerase (PARP), or poly-(ADP-ribose) synthetase, is a nuclear enzyme that consumes NAD when activated by DNA damage. The role of PARP in the pathogenesis of traumatic brain injury (TBI) is unknown. Using a controlled cortical impact (CCI) model of TBI and mice deficient in PARP, the authors studied the effect of PARP on functional and histologic outcome after CCI using two protocols. In protocol 1, naive mice (n = 7 +/+, n = 6 -/-) were evaluated for motor and memory acquisition before CCI. Mice were then subjected to severe CCI and killed at 24 hours for immunohistochemical detection of nitrated tyrosine, an indicator of peroxynitrite formation. Motor and memory performance did not differ between naive PARP +/+ and -/- mice. Both groups showed nitrotyrosine staining in the contusion, suggest ing that peroxynitrite is produced in contused brain. In protoco 2, mice (PARP +/+, n = 8; PARP -/-, n = 10) subjected to CCI were tested for motor and memory function, and contusion volume was determined by image analysis. PARP -/- mice demonstrated improved motor and memory function after CC versus PARP +/+ mice (P < 0.05). However, contusion volume was not different between groups. The results suggest a detri mental effect of PARP on functional outcome after TBI. (+info)
Measuring the impact of Parkinson's disease with the Parkinson's Disease Quality of Life questionnaire.
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OBJECTIVES: To assess the validity of the Parkinson's Disease Quality of Life (PDQL) questionnaire, a patient-specific multi-dimensional quality of life measure, in a community-based sample of patients with Parkinson's disease (PI)) using standardized measures of disease severity, depressive symptomatology and cognitive function. DESIGN: A group of 194 patients with probable PD were randomly selected from a community-based register and were invited to self-complete the 37-item PDQL. Disease severity was measured by the disease-specific Webster scale, cognition by the CAMCOG neuropsychological test and depressive symptomatology by the self-report 15-item GDS-15 geriatric depression scale. RESULTS: A total of 136 patients returned completed PDQL questionnaires. Significant differences (P < 0.05) emerged between the pooled PDQL score of patients grouped on the basis of disease severity. Depressive symptoms and cognition were also associated with poorer perceived quality of life as measured by the PDQL. CONCLUSIONS: The results of this study are indicative of the validity of the PDQL as an important additional measurement which reflects the impact of PD from the patient perspective. It shows poorer quality of life to be associated with increasing age, disease severity more severe depressive symptomatology and impaired cognitive functioning. However, the responsiveness of this instrument in the evaluation of care in PD remains to be determined. (+info)
Depressive illness, depressive symptomatology and regional cerebral blood flow in elderly people with sub-clinical cognitive impairment.
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BACKGROUND: Depressive illness in dementia is often assumed to be a unitary clinical phenomenon. AIM: To describe changes in patterns of depressive symptomatology with time, and associated changes in cerebral blood flow to the frontal and temporal regions. METHOD AND RESULTS: 397 elderly people with sub-clinical cognitive dysfunction were observed over 3 years. Sixteen percent of them developed dementia during the study The prevalence of depressive symptomatology was higher in this group than in the general population, especially in women, who also had higher recovery rates. A changing profile of depressive symptoms was found in depressed elderly people progressing to dementia, with fewer affective symptoms and increases in agitation and motor slowing. These changes were paralleled by greater reductions in left temporal regional cerebral blood flow than in non-depressed subjects with Alzheimer's disease. CONCLUSION: In dementia, there may be two separate and interacting depressive syndromes whose differentiation may be clinically important. (+info)
Topographical disorientation: a synthesis and taxonomy.
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Over the last century, several dozen case reports have presented 'topographically disoriented' patients who, in some cases, appear to have selectively lost their ability to find their way within large-scale, locomotor environments. A review is offered here that has as its aim the creation of a taxonomy that accurately reflects the behavioural impairments and neuroanatomical findings of this literature. This effort is guided by an appreciation of the models of normative way-finding offered by environmental psychology and recent neuroscience research. It is proposed that several varieties of topographical disorientation exist, resulting from damage to distinct neuroanatomical areas. The particular pattern of impairments that patients evidence is argued to be consonant with the known functions of these cortical regions and with recent neuroimaging results. The conflicting claims of previous reviews of this area are also considered and addressed. (+info)
Poststroke depression correlates with cognitive impairment and neurological deficits.
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BACKGROUND AND PURPOSE: The prevalence of poststroke depression is known to be high, but the knowledge of its neuropsychological correlates is limited. This 12-month prospective study was designed to evaluate the natural history of poststroke depression and to study its neuropsychological, clinical, and functional associates. METHODS: We studied a series of 106 consecutive patients (46 women and 60 men, mean age 65.8 years) with acute first-ever ischemic stroke. The patients underwent a neurological, psychiatric, and neuropsychological examination at 3 and 12 months after the stroke. The psychiatric diagnosis of depression was based on DSM-III-R-criteria. RESULTS: Depression was diagnosed in 53% of the patients at 3 months and in 42% of the patients at 12 months after the stroke. The prevalence of major depression was 9% at 3 months and 16% at 12 months. There was an association between poststroke depression and cognitive impairment; the domains most likely to be defective in stroke-related depression were memory (P=0.022), nonverbal problem solving (P=0.039), and attention and psychomotor speed (P=0.020). The presence of dysphasia increased the risk of major depression. The depressive patients were more dependent in ADL and had more severe impairment and handicap than the nondepressive patients. CONCLUSIONS: More than half of the patients suffer from depression after stroke, and the frequency of major depression seems to increase during the first year. In addition to dysphasia, poststroke depression is correlated with other cognitive deficits. We emphasize the importance of psychiatric evaluation of stroke patients. (+info)
Factors associated with functional decline and improvement in a very elderly community-dwelling population.
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The objective of this study was to analyze the factors associated with functional decline and improvement in a community-dwelling population of people aged 75 years and older. A representative sample of elderly people living at home in the city of Sherbrooke (Quebec, Canada) was assessed yearly on three occasions (1991-1993) by a nurse. A health questionnaire, together with standardized instruments measuring disabilities, cognitive status, and depressive mood, was administered on the three assessments. From the 655 subjects who agreed to participate, a total of 504 subjects completed the study. The most important factors associated with functional decline were the number of days off regular activities (odds ratio (OR) = 1.31), the number of hot meals per day (OR = 1.59), and cognitive status (OR = 0.96), whereas weight loss (OR = 0.37) and living alone (OR = 0.54) were significant protective factors. Previous declines in functional autonomy, cognitive state, or mood were not independent risk factors. The most important factors associated with functional improvement were the disability score (OR = 1.08), previous functional decline (OR = 6.06), and decline in the disability score (OR = 1.09). Perceiving health to be worse than it was the previous year was a significant factor against improvement (OR = 0.24). This study identifies risk factors that can be helpful for targeting high-risk subgroups within the very elderly population who may benefit from a preventive program. (+info)
Structured Interview for Assessing Perceptual Anomalies (SIAPA).
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Clinical descriptions of perceptual and attentional anomalies in schizophrenia emphasize phenomena such as flooding, or inundation, by sensory stimuli. A failure of sensory "gating" mechanisms in the brain is hypothesized to account for these symptoms, and this hypothesis has led to a marked interest in their putative psychophysiological substrates. However, there are no systematic analyses of the phenomenology of these perceptual experiences, nor has the hypothesized connection between the clinical phenomena and their reported psychophysiological substrates been tested. In this investigation, a structured interview instrument was developed to measure perceptual anomalies as distinct from hallucinations and to determine their prevalence across sensory modalities in schizophrenia in 67 schizophrenia subjects and 98 normal controls. The instrument includes Likert ratings of hypersensitivity, inundation, and selective attention to external sensory stimuli. Good interrater agreement, determined from interviews, was obtained. Schizophrenia subjects had significantly higher auditory, visual, and combined scores (i.e., across all modalities) than normal controls did, indicating significantly more perceptual anomalies. For the schizophrenia group, the prevalence of auditory and visual anomalies was significantly greater than the other sensory modalities. The data indicate that the putative phenomenological correlates of sensory gating may be reliably measured and tested with the Structured Interview for Assessing Perceptual Anomalies. (+info)
Category learning and perceptual categorization in schizophrenia.
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The aim of this study was to evaluate category learning in schizophrenia on tests of perceptual abstraction. Participants learned to categorize simple geometrical shapes. The categories were either well-defined (discrete categories, or DCs) or ill-defined (graded categories, or GCs). In DCs, the cues defining category membership can be verbalized in an all-or-none fashion, while in GCs they cannot be defined unambiguously. Three types of learning were used successively: serial presentation of category-exemplars, verbal description, and feedback. After the serial presentation, schizophrenia patients showed a deficit for GCs (p<0.005) but not for DCs (p = 0.98). After the verbal definition of GCs, the difference between schizophrenia patients and controls diminished (p = 0.09). Finally, after the feedback learning of GCs, a significant difference was observed again (p<0.0001), suggesting that schizophrenia patients were impaired in this learning paradigm. The GC-learning impairment after the serial presentation displayed a relationship with the score of the cognitive component assessed with the Positive and Negative Syndrome Scale (r = -0.66). In conclusion, these results suggest that the perceptual stage of abstraction is impaired in schizophrenia. This impairment can be partially compensated by instructions via top-down verbal processes. (+info)