Cognitive function of patients with nasopharyngeal carcinoma with and without temporal lobe radionecrosis

BACKGROUND: Radiotherapy is the primary treatment for nasopharyngeal carcinoma, and temporal lobe necrosis is observed in about 7% of patients after radiotherapy. Although some studies reported that these patients demonstrated cognitive impairment after radiotherapy, it is still unclear if the cognitive deficits are related to the radiation exposure or the radiation-induced necrosis. OBJECTIVE: To compare the cognitive function of patients with and without temporal lobe necrosis after radiotherapy for nasopharyngeal carcinoma. METHODS: A comprehensive neuropsychological battery was administered to 53 patients with nasopharyngeal carcinoma who had completed their radiotherapy at least 1 year previously. As evidenced by magnetic resonance imaging, 31 patients developed necrosis after treatment. Thirty-one age- and education-matched individuals were recruited as normal control subjects. RESULTS: Whereas the performance of patients without temporal lobe necrosis was similar to that of normal control subjects, patients with temporal lobe necrosis demonstrated significant impairment on tests of verbal (P<.001) and visual memory (range, P<.001 to P =.03), language (range, P<.001 to P =.01), motor ability (P =.02), planning (P =.02), cognitive ability (P =.007), and abstract thinking (range, P =.009 to P =.04). However, the performance of patients with necrosis on tests of general intelligence (range, P =.08 to P =.15), attention (range, P =.06 to P =.55), and visual abilities (range, P =.06 to P =.47) was not significantly different from that of normal control subjects and patients without necrosis. CONCLUSIONS: Radiotherapy for nasopharyngeal carcinoma seemed to have adverse but insignificant effects on the cognitive functions of the patients. However, for patients who developed temporal lobe necrosis after radiotherapy, memory, language, motor ability, and executive functions were significantly impaired, although their general intelligence remained relatively intact.     

Reliability and validity of the Japanese version of the Dysexecutive Questionnaire (DEX) in Alzheimer's disease: validation of a behavioral rating scale to assess dysexecutive symptoms in Japanese patients with Alzheimer's disease

BACKGROUND: Both executive cognitive dysfunction and behavioral problems contribute to dysexecutive symptoms in daily life. The aim of the present study was to develop a behavior rating scale for assessing dysexecutive symptoms in Japanese patients with AD. METHOD: The Dysexecutive Questionnaire (DEX), devised by Burgess et al. (1998), was used to evaluate 122 Japanese patients with AD. The factor structure, internal consistency, test-retest reliability, and construct validity of the Japanese version of the DEX were then examined. RESULTS: The Japanese version of the DEX demonstrated a good internal reliability and a good test-retest reliability. Factor analysis revealed three factors that were named 'apathy', 'hyperactivity' and 'planning and monitoring process of the purposive action'. The 'apathy' factor of the DEX was significantly correlated with the 'apathy' score of the Neuropsychiatric Inventory (NPI), while 'planning and monitoring process' factor of the DEX was significantly correlated with the total score of the Frontal Assessment Battery (FAB) and the 'hyperactivity' factor of the DEX was significantly correlated with the 'aggression', 'euphoria' and 'disinhibition' scores of the NPI. CONCLUSIONS: The Japanese DEX is a reliable and valid instrument for assessing executive dysfunction conveniently in real life situations of AD patients. While two factors, 'apathy' and 'hyperactivity', were associated with emotional and behavioral changes, the 'planning and monitoring process' was associated with the cognitive executive function in the patients with AD. These findings suggest that both a neuropsychiatric syndrome and cognitive function contribute to the dysexecutive symptoms experienced by AD patients in daily life.     

Executive dysfunction and apathy predict functional impairment in Alzheimer disease.

OBJECTIVE: The purpose of this study was to examine the extent to which executive cognitive dysfunction and frontally-mediated behavioral disturbances are associated with functional impairment in patients with mild-to-moderate Alzheimer disease (AD). METHODS: Patients with AD (N=45) completed the Mattis Dementia Rating Scale, and patients' caregivers completed the Frontal Systems Behavioral Inventory and a modified form of the Lawton and Brody Activities of Daily Living (ADLs) Questionnaire. RESULTS: Multiple-regression analyses revealed that executive cognitive dysfunction and apathy scores accounted for 44% of the variance in instrumental activities of daily living; executive cognitive dysfunction alone explained 17% of the variance in instrumental ADLs, and apathy scores explained an additional 27%. Executive dysfunction and frontal-behavioral impairment explained 28% of the variance in basic ADLs (BADLs), and, after accounting for executive dysfunction, apathy was the only symptom found to explain additional unique variance in BADLs. CONCLUSION: These findings suggest that specific cognitive and behavioral symptoms are associated with functional impairment in patients with AD.     

Clinical and psychometric distinction of frontotemporal and Alzheimer dementias

BACKGROUND: A proportion of patients who meet the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Associations criteria for Alzheimer disease (AD) have frontotemporal lobar degeneration (FTLD) confirmed at autopsy, with or without concomitant AD. Thus, the clinical phenotypes of the 2 disorders may overlap. OBJECTIVE: To identify clinical and psychometric indicators that distinguish AD from FTLD at initial presentation. DESIGN: Longitudinal study of memory and aging. SETTING: Alzheimer's Disease Research Center, Washington University School of Medicine. PARTICIPANTS: Forty-eight clinically well-characterized cases of autopsy-confirmed FTLD (27 with psychometric testing results) were compared with 27 autopsy-confirmed AD cases. RESULTS: Behavioral abnormalities, particularly impulsivity (P<.001), disinhibition (P<.001), social withdrawal (P = .01), and progressive nonfluent aphasia, distinguished individuals with FTLD from those with AD. The individuals with FTLD performed better than those with AD on a visual test of episodic memory (P = .01), but worse on word fluency (P = .02) (performance correlated with aphasic features). Other cognitive and clinical features, including executive dysfunction and memory impairment, were comparable between the FTLD and AD groups. Concomitant histopathological AD was present in 11 of the 48 individuals with FTLD. CONCLUSIONS: Clinical and cognitive features of FTLD may overlap with AD, although behavioral and language difficulties distinguish those with FTLD. Memory loss in those with FTLD may in part reflect word-finding difficulties stemming from language dysfunction. Compounding the overlap of FTLD and AD clinical phenotypes is the presence of histopathological AD in almost one fourth of individuals with FTLD.     

Parkinsonianlike signs and risk of incident Alzheimer disease in older persons

BACKGROUND: Parkinsonianlike signs are common in older persons, but little is known about how their severity or rate of progression is related to the development of Alzheimer disease (AD) or decline in cognition. OBJECTIVE: To examine the association of progression of parkinsonianlike signs with incident AD and cognitive decline. DESIGN: Longitudinal cohort study. PARTICIPANTS AND SETTING: For up to 8 years, 824 older Catholic clergy members without clinical evidence of AD or Parkinson disease at baseline underwent annual clinical evaluations that included a modified version of the Unified Parkinson's Disease Rating Scale (UPDRS), detailed cognitive function testing, and clinical classification of AD. MAIN OUTCOME MEASURES: Clinically diagnosed AD and change in global and specific measures of cognitive function. RESULTS: During an average of 4.6 years of observation, 114 persons developed AD. The global UPDRS score increased in 79% of participants, who were divided into tertiles with the least, moderate, or most rapid progression. We examined the relationship of progression to disease risk in a proportional hazards model that controlled for baseline global UPDRS and demographic variables. Compared with the 21% without progression, risk of AD more than doubled in the subgroup with the least progression (P =.08), more than tripled in the moderate subgroup (P =.02), and increased more than 8-fold in the subgroup with the most rapid progression (P<.001). This effect was mainly due to worsening gait and rigidity. Rate of change on the global UPDRS measure was inversely correlated with rate of change on a global measure of cognitive function (r = -0.64). CONCLUSION: Progression of parkinsonianlike signs in old age is associated with decline in cognitive function and the development of AD.     

Depression in burn reconstruction patients: symptom prevalence and association with body image dissatisfaction and physical function

OBJECTIVE: This study investigated the prevalence and the clinical correlates of symptoms of depression among burn reconstruction patients. METHOD: A sample of 224 burn reconstruction patients completed the Beck Depression Inventory (BDI), the SF-36 Health Survey and the Satisfaction with Appearance Scale. RESULTS: The prevalence of at least mild to moderate symptoms of depression (BDI > or =10) was 46%. Female patients were disproportionately represented in this burn reconstruction population (46%) compared to all survivors from the burn center (29%; P<.001) and compared to a national sample of burn survivors (27%; P<.001). Compared to males, female patients presented for consultation much longer after a burn injury (P<.001), tended to have smaller burns (P=.06) and were less likely to have facial burns (P=.08). Depressive symptoms were largely predicted by body image dissatisfaction (beta=.58; P<.001), with additional variance predicted by physical function (beta=-.13; P=.07). The effect of patient and burn injury variables on depressive symptoms was mediated by body image dissatisfaction and physical function. CONCLUSION: The high prevalence of significant symptoms of depression in burn reconstruction patients and their relationship with body image suggest the importance of the routine psychological screening of patients seeking reconstruction services.     

Cerebrospinal fluid tau and beta-amyloid 42 proteins identify Alzheimer disease in subjects with mild cognitive impairment

CONTEXT: Cerebrospinal fluid tau protein and beta-amyloid 42 (Abeta42) protein are altered even in very mild Alzheimer disease (AD). So far, few data exist for subjects with mild cognitive impairment (MCI). OBJECTIVE: To investigate the potential of cerebrospinal fluid tau and Abeta42 for predicting progression from MCI to AD in a longitudinal study of 28 patients with MCI who received follow-up for 18 months. DESIGN: An 18-month prospective study. SETTING: Clinical follow-up study of community-residing subjects with MCI. MAIN OUTCOME MEASURES: Cerebrospinal fluid tau and Abeta42 concentrations were measured using enzyme-linked immunosorbent assay at baseline. The potential of both biomarkers was evaluated to predict the progression to dementia, the end point of this study, using multiple logistic regression analysis. RESULTS: Of 28 subjects with MCI, 12 progressed to dementia (2 to frontotemporal dementia; 10 to AD). Six subjects had progressive MCI, and 10 subjects showed stable MCI. Cerebrospinal fluid tau levels were significantly elevated in patients who progressed to probable AD (P =.002) and subjects with progressive MCI (P =.003) compared with subjects who had stable MCI. Cerebrospinal fluid Abeta42 levels were significantly lower in patients who progressed to probable AD (P =.007) and those with progressive MCI (P =.04) than in subjects with stable MCI. Logistic regression analysis identified elevated tau protein level as a predictor of cognitive deterioration (P =.02), whereas a delayed verbal recall score at baseline was significantly associated with the development of probable AD (P =.03). CONCLUSION: Our results indicate that altered tau and Abeta42 concentrations may be detectable in subjects who are clinically diagnosed as having MCI but demonstrate the pathological changes of AD.     

Cerebrospinal fluid homovanillic acid is correlated to psychotic features in neurological patients with delirium

OBJECTIVE: The aim of this study was to determine if cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) are related to the clinical features of delirium in a group of patients with acute onset neurological illness. METHODS: Fifty-one patients with probable acute brain infection were classified as delirious and nondelirious according to Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) and Delirium Rating Scale (DRS). CSF HVA concentration was analyzed by high-performance liquid chromatography. RESULTS: Delirium was present in 60.8% of the total sample. HVA levels were not significantly different between delirious and nondelirious patients. Remarkably, patients with psychotic symptoms shown higher levels of CSF HVA as compared to nonpsychotic patient values. In addition, HVA levels were positively correlated to specific items of DRS such as delusions (r=0.463, P=.001), hallucinations (r=0.438, P=.001), cognitive dysfunction (r=0.286, P=.042) and fluctuation of symptoms (r=0.280, P=.046) in the total sample. Subanalyses excluding patients taking antipsychotic drugs revealed that HVA CSF levels were higher in those patients with delusions, and furthermore, the dopamine metabolite remained positively correlated to delusion subscale of DRS. CONCLUSIONS: Our results suggest that psychotic symptoms in delirious patients may be related to increased dopamine neurotransmission, as reflected by increased CSF HVA concentration, providing direct evidence to support the dopaminergic theory of psychosis.     

Corpus callosum atrophy,white matter lesions,and frontal executive dysfunction in normal aging and Alzheimer's disease. A community-based study: the Tajiri Project

BACKGROUND AND OBJECTIVES: Cerebral MRIs of normal aging and Alzheimer's disease (AD) frequently reveal corpus callosum (CC) atrophy, white matter hyperintensity (WMH), and hippocampal atrophy. However, their relationship or the relationship between these findings and cognitive function has not been fully studied. We investigated the relationship between CC atrophy, WMH, and hippocampal atrophy, together with frontal executive dysfunction in both normal aging and AD. METHOD: We examined 170 randomly selected residents from a designated community: 99 Clinical Dementia Rating (CDR) 0 (healthy, control group, HC) participants, 54 CDR 0.5 (very mild AD) patients, and 17 CDR 1 & 2 (probable AD) patients. By means of MRI, WMH and CC atrophy were visually rated. Four portions of the CC and the hippocampal width were measured. A Mini-Mental State Examination and Cognitive Abilities Screening Instrument (CASI) were performed to assess global function. For the frontal function, the CASI subitems of attention and word fluency, letter-based fluency, the Digit Symbol test of the WAIS-R, and Trail Making Tests were performed. RESULTS: Those patients with CDR 1 & 2 had both hippocampal and CC atrophy, whereas the CDR 0.5 patients had only hippocampal atrophy. Frontal executive dysfunction was associated with CC atrophy in both the HC and AD groups. Significant Spearman correlations were noted between CC atrophy and WMH in both groups. The combined effect of CC atrophy and WMH was noted only in the verbal fluency test in the HC group. CONCLUSION: In both groups, CC atrophy was associated with frontal executive dysfunction. The combined effect of CC atrophy and WMH in normal aging was probably due to subclinical ischemic conditions.     

The relationship between self-awareness of neurobehavioral symptoms, cognitive functioning, and emotional symptoms in multiple sclerosis

OBJECTIVE: To examine self-awareness of neurobehavioral symptoms in multiple sclerosis (MS) across three domains of function (apathy, disinhibition, and executive control), and examine the relationship between self-awareness and cognitive functioning. METHODS: Twenty-six individuals with MS completed neuropsychological testing, measures of emotional functioning, and self-ratings of neurobehavioral symptoms using the Frontal Systems Behavior Scale (FrSBe), a 46-item questionnaire with subscales assessing frequency of symptoms in executive dysfunction, disinhibition, and apathy. Informants' ratings of the FrSBe were also obtained. Decreasing differences between patient and informant reports on each subscale of the FrSBe (concordance) indicate higher levels of self-awareness. RESULTS: Results showed significant positive correlations between cognitive abilities and self-awareness of executive dysfunction and disinhibition. In contrast, affect symptomatology (measures of anxiety and depression) were negatively correlated with self-awareness of executive dysfunction. CONCLUSIONS: Level of self-awareness of neurobehavioral symptoms in MS is related to level of cognitive impairment In addition, symptoms of depression and anxiety reduced the accuracy of self-reporting. Thus, a clinician who relies on self-reports in creating an evaluation and treatment plan should consider the patient's cognitive and emotional states.     

Greater impairment of ability in the divided attention task is seen in Alzheimer's disease patients with depression than in those without depression

BACKGROUND: Recent studies have emphasized specific deficits of attention and executive functions, such as those of cognitive flexibility, divided attention, in geriatric patients with depression. In Alzheimer's disease (AD), depressive symptoms are known to occur even from an early stage of the disease. However, the nature of the impairment of executive functions in depression associated with AD remains unclear, because of the frequent occurrence of the apathy syndrome as a major confounding factor. METHOD: In this study, we conducted a comprehensive comparative neuropsychological assessment in AD patients with (n=21) and without (n=21) depression. The diagnosis of depression was based on provisional criteria proposed by Olin's group. RESULTS: In terms of apathy symptoms, both groups had a similar degree of deficits, which were mild as assessed according to Neuropsychiatric Inventory criteria. While no significant differences were observed in regard to the scores in general intellectual functioning, episodic memory and some attention and executive tasks between the two groups, AD patients with depression showed significantly lower scores in several attention and executive function tasks, such as the dual-task performance task administered to assess the capacity for divided attention, and the cognitive flexibility (Trail Making Test; Part B), than AD patients without depression. CONCLUSIONS: Our results suggest that depressive symptoms in AD patients increase the deficits of cognitive flexibility and divided attention. This is the first study to report a correlation between depressions, diagnosed based on the provisional criteria for depression in AD by Olin's group, and an impaired capacity for divided attention in AD patients.     

Examining the Relationship between Executive Functions and Restricted,Repetitive Symptoms of Autistic Disorder

The executive function theory was utilized to examine the relationship between cognitive process and the restricted, repetitive symptoms of Autistic Disorder (AD). Seventeen adults with AD were compared to 17 nonautistic controls on a new executive function battery (Delis-Kaplin Executive Function Scales). Restricted, repetitive symptoms were measured by a variety of instruments (i.e., the Autism Diagnostic Observation Schedule, Autism Diagnostic Interview-Revised, Gilliam Autism Rating Scale, and the Aberrant Behavior Checklist). The study replicated the executive function profile that has been reported in adults with AD. In addition to the replication findings, the study found several executive processes (i.e., cognitive flexibility, working memory, and response inhibition) were highly related to the restrictive, repetitive symptoms of AD; whereas, other executive process (i.e., planning and fluency) were not found to be significantly correlated with restricted, repetitive symptoms. Similarly, we found an executive function model consisting of relative strengths and deficits was the best predictor of restricted, repetitive symptoms of autism. The implications for the executive function theory and how the theory predicts core symptoms of autism are discussed.     

Differences between Pick disease and Alzheimer disease in clinical appearance and rate of cognitive decline

OBJECTIVES: To define the cognitive characteristics of Pick disease (PcD), and to determine which features distinguish PcD from Alzheimer disease (AD), in a cross-sectional and longitudinal study. METHODS: The participants were 44 patients with PcD (10 pathologically verified), 121 patients with AD (14 pathologically verified), and 60 normal control subjects. We obtained information regarding the initial symptom of dementia from each patient's caregiver, estimated global dementia severity by the Blessed Dementia Scale and the Activities of Daily Living Scale, and assessed specific cognitive domains by administering 10 tests of memory, language, visuospatial, and reasoning abilities and selective attention. RESULTS: Among initial symptoms reported by caregivers, personality change and language impairment were significantly more common in PcD than AD; deficits in memory were common in both groups but more prevalent in AD (P<.001). At initial cognitive testing, the scores of patients with PcD were inferior to those of normal controls on all tests, except on a measure of visuospatial function; the scores of patients with AD were inferior to those of controls on all tests. Patients with PcD were superior to patients with AD on measures of explicit memory (P<.001) and visuospatial function (P = .001) but had greater impairments on the Activities of Daily Living Scale (P<.05). During the course of illness, patients with PcD declined significantly faster than those with AD on language tests and on global measures of dementia severity (P<.05), whereas measures of explicit memory and visuospatial and reasoning abilities worsened equally in both patient groups. CONCLUSIONS: There is a characteristic cognitive profile and course of dementia in PcD. Nonetheless, cognitive test performance does not clearly distinguish PcD from AD.     

Sleep in Wilson's disease: a polysomnography-based study

Wilson's disease (WD) has neuro-anatomical, pathophysiological and neurochemical basis for sleep disturbances. The aim of the study was objective evaluation of the frequency and nature of sleep abnormalities using polysomnography (PSG) in patients with WD. The study included 25 subjects with WD (males, 18; age , 24.4 ± 9.25 years) and 25 healthy controls (all males; age, 33.1 ± 9.7 years). After phenotypic assessment and magnetic resonance imaging (MRI), sleep-related questionnaires were administered, and PSG was performed. Patients had significantly reduced total sleep-time (P=.001), sleep-efficiency (P=.001), percentage of deep sleep (P=.01), and REM-sleep (P=.04) with prolonged sleep-onset latency (P=.05) and latency to stage 2 (P=.02). Subgroup analyses of patients based on demographic and clinical parameters were done. Men had significantly more bradycardia both during awake (P=.002) and sleep (P=.03) states. Younger patients (<20 years) had frequent tachycardia (P=.01), higher Periodic Limb Movement (PLM) Index (P=.01) and lesser REM% sleep (P=.05). Patients on de-coppering therapy had prolonged REM-sleep-onset latency (P=.03) and mixed apnea events (P=.04). The isolated limb movements were more in the severe form of disease (P=.05) and in patients taking anticonvulsants (P=.03). This study, the first of its kind in literature, revealed significant sleep disturbances in patients with Wilson's disease.     

Anosognosia and Alzheimer's disease: the role of depressive symptoms in mediating impaired insight

The relation between anosognosia and dementia severity in Alzheimer's disease (AD) has been unclear. We constructed a measure that quantified the difference between the perceptions of deficits of patients with AD (n = 23) and ratings from a knowledgeable informant as a measure of anosognosia. There was no correlation between dementia severity and anosognosia. However, dementia severity was positively correlated with the degree of anosognosia after controlling for depressive symptomatology (p =.03). Post-hoc analyses, also controlling for depressive symptoms, indicated that higher levels of anosognosia were associated with lower performance on specific cognitive tasks. These results suggest depressive symptoms may confound the relationship between anosognosia and dementia severity.     

Early onset Alzheimer's disease is associated with a distinct neuropsychological profile

Alzheimer's disease (AD) in younger patients is associated with a higher prevalence of atypical symptoms. We examined neuropsychological performance according to age-at-onset. We assessed cognition in 172 patients with AD (81 early and 91 late onset) in five cognitive domains (memory, language, visuo-spatial functioning, executive functioning, attention). Dementia severity was assessed using the Mini-Mental State Examination (MMSE) and global cognitive decline using Cambridge Cognitive Examination (CAMCOG). Analyses of variance were performed with age-at-onset as between-subjects factor, and gender and education as covariates. Analysis was repeated after stratification for dementia severity (based on median MMSE). In early onset AD, age (mean ± SD) was 60 ± 4 years; 44 (54%) were female. In late onset AD, age was 72 ± 5 years; 47 (52%) were female. Dementia severity and global cognitive decline did not differ between groups (early onset: MMSE: 20 ± 5, CAMCOG: 69 ± 15, late onset: MMSE: 21 ± 5, CAMCOG: 70 ± 15; p > 0.05). Early onset patients performed worse than late onset patients on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01). Late onset patients performed worse on memory, although not significantly (p = 0.11). Stratification for dementia severity showed that in mildly demented early onset patients, memory function was remarkably preserved compared to late onset patients (p < 0.01). In moderate AD, differences in memory function disappeared, but early onset patients performed worse on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01) than late onset patients. Adjustment for APOE left results unchanged. In conclusion, early onset AD presents with a different cognitive profile and the disease course seems different. Relative sparing of memory function in early stages stresses the need to adequately test other cognitive domains.     

Laboratory findings in emergently medicated psychiatry patients

OBJECTIVE: To determine routine laboratory differences between patients with severe psychomotor agitation who require emergency intramuscular (IM-medicated patients) medication and those who do not (non-IM-medicated patients). METHOD: A retrospective chart review of patients 18 years or older who went to a psychiatry emergency service over a 30-day period was performed. Demographic and laboratory variables were compared between IM- and non-IM-medicated patients. RESULTS: Emergently medicated patients (n=35) were older than non-IM-medicated patients (n=179) (42.6 vs 34.3 years, P<.001). Patients receiving emergency IM medications had higher leukocyte (WBC) count (P=.04), blood urea nitrogen (P=.001), creatinine (P=.01), glucose (P=.009), aspartate aminotransferase (P<.001), alanine aminotransferase (P=.01), and electrocardiogram QTc interval (P=.03). They were also more likely to have abnormal levels of potassium (P<.05), glucose (P<.05), aspartate aminotransferase (P<.001), and alanine aminotransferase (P<.05). CONCLUSIONS: Emergently medicated patients in this psychiatry emergency service were more likely to be older and more likely to have abnormal laboratories vs other adult patients.     

Beneficial effects of testosterone replacement for the nonmotor symptoms of Parkinson disease

OBJECTIVE: To investigate whether a single daily dose of testosterone replacement gel has beneficial effects on testosterone deficiency symptoms, cognitive function, nonmotor symptoms of Parkinson disease (PD), and motor symptoms of PD. BACKGROUND: Recently it has been observed that testosterone replacement therapy improves refractory nonmotor symptoms in testosterone-deficient men with PD. Many of the symptoms of testosterone deficiency are nonspecific and overlap with the nonmotor symptoms of PD, such as decreased enjoyment of life, lack of energy, sexual dysfunction, and depression. Replacement therapy for men with PD and comorbid testosterone deficiency may be an important addition to antiparkinsonian management strategies. METHODS: A prospective open-labeled pilot study of testosterone topical gel (5 g of AndroGel; Unimed Pharmaceutical Inc, Deerfield, Ill) administered daily to testosterone-deficient (free testosterone <80 pg/mL) men with PD. All 10 patients were followed up for 1 month and 6 patients were followed up for a total of 3 months. Patients were administered a battery of testosterone deficiency questionnaires, cognitive studies, and scales of PD nonmotor and motor function at baseline, 1, and 3 months. RESULTS: With the daily transdermal testosterone gel, patients had an average increase in levels of free testosterone from baseline (53 pg/mL) to a 1-month follow-up visit (131 pg/mL; P =.06) and to a 3-month follow-up visit (98 pg/mL; P =.04). Testosterone deficiency symptoms improved in these patients (St Louis Testosterone Deficiency Questionnaire) from baseline (7.9 deficiency symptoms) to 1 month (5.6 deficiency symptoms, P =.04) and 3 months (5.8 deficiency symptoms, P =.08). The Unified Parkinson's Disease Rating Scale IV showed improvement at 1 month (P =.008). Additionally, there were trends toward improvement in the following scales: Unified Parkinson's Disease Rating Scale I at the 3-month follow-up (P =.09), Letter Fluency at the 3-month follow-up (P =.08), and the Hamilton Anxiety Scale at the 1-month follow-up (P =.09). CONCLUSIONS: A daily dose of transdermal testosterone gel improved testosterone deficiency symptoms in men with PD. Although there were trends in improvement in other nonmotor and motor symptoms of PD, future placebo control studies will need to be powered to answer these important questions. Whether testosterone deficiency is simply a comorbidity in PD or whether it plays a role in the pathogenesis of disease also remains for future study.     

Early-stage visual processing and cortical amplification deficits in schizophrenia

BACKGROUND: Patients with schizophrenia show deficits in early-stage visual processing, potentially reflecting dysfunction of the magnocellular visual pathway. The magnocellular system operates normally in a nonlinear amplification mode mediated by glutamatergic (N-methyl-D-aspartate) receptors. Investigating magnocellular dysfunction in schizophrenia therefore permits evaluation of underlying etiologic hypotheses. OBJECTIVES: To evaluate magnocellular dysfunction in schizophrenia, relative to known neurochemical and neuroanatomical substrates, and to examine relationships between electrophysiological and behavioral measures of visual pathway dysfunction and relationships with higher cognitive deficits. DESIGN, SETTING, AND PARTICIPANTS: Between-group study at an inpatient state psychiatric hospital and outpatient county psychiatric facilities. Thirty-three patients met DSM-IV criteria for schizophrenia or schizoaffective disorder, and 21 nonpsychiatric volunteers of similar ages composed the control group. MAIN OUTCOME MEASURES: (1) Magnocellular and parvocellular evoked potentials, analyzed using nonlinear (Michaelis-Menten) and linear contrast gain approaches; (2) behavioral contrast sensitivity measures; (3) white matter integrity; (4) visual and nonvisual neuropsychological measures, and (5) clinical symptom and community functioning measures. RESULTS: Patients generated evoked potentials that were significantly reduced in response to magnocellular-biased, but not parvocellular-biased, stimuli (P = .001). Michaelis-Menten analyses demonstrated reduced contrast gain of the magnocellular system (P = .001). Patients showed decreased contrast sensitivity to magnocellular-biased stimuli (P<.001). Evoked potential deficits were significantly related to decreased white matter integrity in the optic radiations (P<.03). Evoked potential deficits predicted impaired contrast sensitivity (P = .002), which was in turn related to deficits in complex visual processing (P< or =.04). Both evoked potential (P< or =.04) and contrast sensitivity (P = .01) measures significantly predicted community functioning. CONCLUSIONS: These findings confirm the existence of early-stage visual processing dysfunction in schizophrenia and provide the first evidence that such deficits are due to decreased nonlinear signal amplification, consistent with glutamatergic theories. Neuroimaging studies support the hypothesis of dysfunction within low-level visual pathways involving thalamocortical radiations. Deficits in early-stage visual processing significantly predict higher cognitive deficits.     

Metabolic correlates of executive dysfunction

This study was designed to examine the correlations between resting-state brain glucose metabolism (CMRglc), as measured with Positron Emission Tomography and performance on executive function tasks in Alzheimer's disease (AD), while taking into account the severity of cognitive deterioration. We addressed this issue in 50 AD patients, classified as very mild (n = 22) and mild (n = 28) AD on the basis of an extensive neuropsychological battery. Thirteen healthy subjects were selected as controls for the neuropsychological measures. Statistical Parametric Mapping (SPM) was used to examine voxel-wise correlations between CMRglc and scores on selected cognitive tests of executive functions: the Stroop Test, the Trail Making Test, the Dual Task and the Phonemic Fluency, while correcting for age and global CMRglc. All analyses were done separately for the two AD subgroups. The very mild AD patients showed significant associations between Stroop and Trail Making Test scores and prefrontal regions metabolism, whereas the mild AD patients exhibited more widely distributed cognitive-metabolic correlations extending to the posterior brain regions. These data suggest that a large cortical network is implicated in executive dysfunction in AD, and that the pattern of cognitive-metabolic correlations varies according to disease severity.