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PubMed1996

Changes in local cerebral blood flow by neuroactivation and vasoactivation in patients with impaired cognitive function.

Imaging of local cerebral blood flow (lCBF) may serve as an important supplementary tool in the aetiological assessment of dementias. In early or preclinical disease, however, there are less characteristic changes in lCBF. In the present study it was investigated whether vasoactivation or neuroactivation may produce more pronounced local lCBF deficits. Local CBF was investigated by using technetium-99m hexamethylpropylene amine oxime and single-photon emission tomography (SPET) in 80 patients (50 with mild cognitive impairment and 30 with dementia of Alzheimer type (DAT), all without evidence of cerebrovascular disease) at rest (baseline) and during activation. In 31 studies patients underwent vasomotor activation with acetazolamide, while 62 studies were performed under cognitive challenge (neuroactivation by labyrinth task). Cortical activity relative to that of cerebellum increased significantly in a right temporal region and tended to increase in other cortical regions upon vasoactivation. In contrast, neuroactivation reduced cortical activity relative to that of cerebellum in several left and right temporal and in left parietal regions. Visual classification of SPET images of patients with probable DAT by three observers resulted in a reduction of the number of definitely abnormal patterns from 9/12 to 4/12 by vasoactivation and an increase from 10/18 to 15/18 by neuroactivation. Correspondingly, abnormal ratings in patients with mild cognitive dysfunction were reduced from 7/19 to 5/19 by vasoactivation and were increased from 12/21 to 18/21 by neuroactivation. In conclusion, vasoactivation does not enhance local relative perfusion deficits in patients with cognitive impairment of non-vascular aetiology, whereas neuroactivation by labyrinth task produces more pronounced local flow differences and enhances abnormal patterns in lCBF imaging.

Acetazolamide↗

PubMed2006

[Trichloroethylene intoxication presenting with temporal seizures].

INTRODUCTION: Trichloroethylene (TCE) is extensively used as a degreasing agent in the metal industry and as a solvent for organic compounds. Its neurotoxicity (with respect to both the peripheral and central nervous systems) is now widely acknowledged. OBSERVATION: Here, we report the case of a 32-year-old male drug addict presenting temporal seizures after "huffing" TCE (i.e. voluntary inhalation). The patient also deve loped a "psycho-organic syndrome" which included cognitive dysfunction (with memory disorders in particular) and personality changes. These disorders had not been noticed by the patient's wife prior to the last episode of inhalation. Four months later, the cognitive disorders had stabilized and no further seizures had been observed. CONCLUSION: The patient's overall clinical picture (notably featuring neuropsychological disorders) and electroencephalographic and brain imaging data argue in favor of a selective effect of TCE on the temporal lobe.

Adult↗

PubMed2000

Subtle brain damage cannot be detected by measuring neuron-specific enolase and S-100beta protein after carotid endarterectomy.

OBJECTIVE: To assess whether subtle brain damage after carotid endarterectomy could be detected using serum levels of neuron-specific enolase (NSE) or S-100beta protein. DESIGN: Prospective noninterventional study. SETTING: University hospital. PARTICIPANTS: Twenty-two patients undergoing carotid endarterectomy and 16 patients undergoing repair of abdominal aortic aneurysm. INTERVENTIONS: Serum levels of NSE and S-100beta protein were measured in all patients before surgery and postoperatively at 12, 24, 36, and 48 hours. In patients undergoing carotid endarterectomy, neuropsychologic testing was performed before surgery and postoperatively at discharge from the hospital and after 3 months using a neuropsychologic test battery. MEASUREMENTS AND MAIN RESULTS: Compared with abdominal aortic surgery patients, the preoperative serum concentration of NSE was significantly higher in carotid artery surgery patients. Postoperatively, the NSE serum level decreased significantly after uncomplicated carotid artery surgery, and the level was then similar to that in the aortic surgery patients. Before operation, the S-100beta protein levels were similar in the two groups, but a significant increase was seen in aortic surgery patients postoperatively. Neuropsychologic testing after uncomplicated carotid artery surgery revealed cognitive dysfunction in 2 of 20 (10%) of the patients after 5 days and 3 of 16 (19%) of the patients after 3 months. There was no correlation between the change in cognitive function and the changes in blood levels of either NSE or S-100 protein. CONCLUSIONS: Subtle brain damage after carotid artery surgery could not be detected by measuring blood levels of NSE and S-100beta protein. The NSE level was significantly higher before carotid artery surgery and decreased postoperatively to the level observed in aortic surgery.

Aged↗

PubMed2004

Cell-density-dependent regulation of neural precursor cell function.

Stress-induced reductions of neural precursor cells from the subgranular zone of the hippocampal dentate gyrus have been linked to impaired neurogenesis and cognitive dysfunction. Given the importance of redox state in regulating multiple damage-responsive pathways in the CNS, we hypothesize that oxidative stress plays a major role in affecting neurogenesis and subsequent cognitive function after cell injury/depletion. Using an in vitro system, we showed that the level of reactive oxygen species (ROS), which depend critically on changes in cell density, were significantly higher in neural precursor cells when compared with other primary and transformed cell lines. ROS were significantly elevated ( approximately 4-fold) under low- (<1 x 10(4) cells per cm(2)) versus high-density (>1 x 10(5) cells per cm(2)) conditions. Higher ROS levels found at lower cell densities were associated with elevated proliferation and increased metabolic activity. These ROS were likely a result of altered mitochondrial function that ultimately compromised the growth rate of cells. At high cell densities, intracellular ROS and oxidative damage were reduced in concert with an increased expression of mitochondrial superoxide dismutase 2. Our finding that DNA-damage-induced depletion of neural precursor cells in the subgranular zone of mice also led to increased ROS and altered proliferation validated our in vitro system. Increased ROS and proliferation associated with the reduction of precursor cell numbers both in vitro and in vivo could be reversed with the antioxidant alpha-lipoic acid. These data showed that neural precursor cells were predisposed to microenvironmental cues that regulate redox-sensitive pathways to control cellular proliferation after CNS damage.

Animals↗

PubMed2004

Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study.

Renal impairment is associated with an increased risk of carotid atherosclerosis and stroke, determinants of cognitive dysfunction and dementia. The purpose of this study was to determine whether moderate renal impairment is associated with incident dementia among community-dwelling older adults. Participants in the Cardiovascular Health Cognition Study without prevalent dementia (n = 3349) were included in the analysis. Incident dementia was confirmed through neurologic testing. Renal function at baseline was estimated by the inverse of serum creatinine (1/SCr); moderate renal impairment was defined as SCr > or = 1.3 mg/dl for women and > or = 1.5 mg/dl for men. Cox regression models were used to estimate the association of renal impairment with incident dementia. Because SCr is also a function of muscle mass, the authors determined whether the relationship between SCr and dementia was particularly strong among individuals without severe co-morbidity at baseline, as reflected by self-reported general health status. There were 477 incident dementia cases over a median 6 yr follow-up. After adjustment for potential confounders, moderate renal insufficiency was associated with a 37% increased risk of dementia (95% CI = 1.06 to 1.78). Similarly, a 0.5-unit decrement in 1/SCr (equivalent to an increase in SCr from 1.0 to 2.0 mg/dl) was associated with a 26% increased risk (95% CI = 1.02 to 1.60). These associations were present only among the 84% of older adults who reported good-excellent health. Among those in good-excellent health, higher SCr was associated with vascular-type dementia but not Alzheimer-type dementia. Moderate renal impairment, reflected by a higher SCr, is associated with an excess risk of incident dementia among individuals in good-excellent health. Strategies to prevent or delay the onset of dementia in patients with moderate renal impairment are needed.

Aged↗

PubMed1998

Psychosis in Alzheimer's Disease.

The risk of psychotic symptoms in patients with Alzheimer's disease (AD) has been noted since the first case description of AD in 1907. Recent studies suggest that approximately a third of AD patients manifest psychosis at sometime during the course of their illness. Differentiating psychotic symptoms from the direct effects of cognitive dysfunction in AD can be challenging for clinicians and researchers. Nonetheless, the identification and treatment of such symptoms may be critical, as AD patients with psychosis may have a more rapid cognitive and functional decline, impose greater caregiver burden, and may be at increased risk of early institutionalization. Due to the potential side effects from neuroleptic medications, nonpharmacologic approaches to treatment should be considered, including environmental and behavioral modification and caregiver education. Some pharmacologic interventions may be necessary for symptoms not alleviated by these approaches, with specific elderly data for quetiapine and risperidone. Because there is no evidence for differential efficacy among the various neuroleptic medications, choice of an antipsychotic should be based on the side effect profiles of available medications weighed against the particular characteristics and situation of the individual patient.

Journal Article↗

PubMed1997

The relationship of antiphospholipid antibodies to cognitive function in patients with systemic lupus erythematosus.

OBJECTIVE: To examine the relationship between antiphospholipid antibody positivity (expressed as the lupus anticoagulant) and cognitive dysfunction in patients with systemic lupus erythematosus (SLE). METHODS: Cross-sectional comparisons of lupus anticoagulant (LA) positive (N = 39) and negative (N = 79) patients and controls (N = 35) on a cognitive test battery; 22 LA-positive and 53 LA-negative patients who had never experienced neuropsychiatric events (never-NP-SLE) were also compared separately. RESULTS: LA-positive patients were 2 to 3 times more likely than were LA-negative patients to be designated as cognitively impaired. As a group, LA-positive patients, particularly those in the never-NP-SLE group, demonstrated lower performance primarily on tasks of verbal memory, cognitive flexibility, and psychomotor speed. CONCLUSIONS: LA positivity is associated with subclinical nervous system compromise, and a pattern of deficits compatible with subcortical involvement, possibly on the basis of ongoing LA-related microthrombotic events or vasculopathy.

Adult↗

PubMed1992

Hypersensitivity to scopolamine in the elderly.

Scopolamine hydrobromide, 0.43 mg/70 kg, was administered by subcutaneous injection to ten young and ten elderly subjects. A comprehensive neuropsychological test battery was used to assess the effects of scopolamine, as compared to placebo, on cognitive function. As previously reported for this group of young subjects, scopolamine significantly impaired performance on tests of recent memory and visuospatial praxis. The same effects were observed in the elderly subjects, but the magnitude of the effects was much larger. The scopolamine injections produced significant psychomotor slowing in the elderly, whereas higher doses of the drug are required to produce this effect in young subjects. In both young and old subjects scopolamine failed to affect immediate memory, language function, object sorting, and the frequency of intrusion errors (although trends toward an effect were more apparent in the elderly). Remote memory, tested in the elderly only, was also unaffected. The results suggest that scopolamine's cognitive effects are quantitatively more pronounced in elderly subjects than young subjects, but that they are qualitatively similar and do not constitute a valid model for the cognitive dysfunction associated with Alzheimer's disease.

Adolescent↗

PubMed2005

Cognitive decline and dementia in diabetes--systematic overview of prospective observational studies.

AIMS/HYPOTHESIS: We systematically reviewed and summarised prospective data relating diabetes status to changes in cognitive function over time. METHODS: Published reports of longitudinal studies that described assessment of cognitive function in people with diabetes were sought. Studies were included if they assessed cognitive function in participants with diabetes at the beginning and at follow-up. Studies were excluded if they had (1) a follow-up period of less than 1 year, (2) a rate of loss to follow-up in excess of 30%, or (3) described selected subgroups. Change in cognitive function was recorded as either the mean change in score and/or the proportion of individuals developing various degrees of change in cognitive function. A pooled estimate was calculated for the latter. RESULTS: Of 1,165 abstracts and titles initially identified, 25 articles met the inclusion and exclusion criteria. Individuals with diabetes had a 1.2- to 1.5-fold greater change over time in measures of cognitive function than those without diabetes. When assessed by the Mini-Mental State Exam and the Digit Symbol Span tests, a diagnosis of diabetes increased the odds of cognitive decline 1.2-fold (95% CI 1.05-1.4) and 1.7-fold (95% CI 1.3-2.3), respectively . The odds of future dementia increased 1.6-fold (95% CI 1.4-1.8). CONCLUSIONS/INTERPRETATION: Compared to people without diabetes, people with diabetes have a greater rate of decline in cognitive function and a greater risk of cognitive decline. Cognitive dysfunction should therefore be added to the list of chronic complications of diabetes.

Cognition↗

PubMed1992

Long-term neuropsychologic sequelae of childhood leukemia: comparison of two CNS prophylactic regimens.

To compare the late neuropsychologic toxicities of CNS prophylaxis in childhood acute lymphoblastic leukemia (ALL), a transversal assessment was performed in two groups of ALL patients and two control groups. The ALL patients had received one of the following CNS prophylaxes: cranial irradiation, 24 Gy and i.t. MTX 10 mg/m2, 6 doses (RT group, n = 25) or i.t. Ara-C 30 mg/m2 and i.t. MTX 10 mg/m2, 10 doses (ChT group, n = 29). The two control groups were: Siblings (Sb, n = 24) and Solid Tumors (ST, n = 22). Intelligence Quotient (IQ), memory, learning, attention and frontal tasks were studied. Comparative analyses between ChT and RT showed no differences in any of the tests. When RT was compared with ST or Sb, RT showed a 10-point lower mean IQ (p greater than 0.05). The results of ChT versus ST or versus Sb were worse in the ChT group. In many tests the differences were statistically significant. Analyses of the 54 ALL patients compared with the 46 controls showed significant differences in all tests except verbal memory and verbal learning. Neuropsychological sequelae of CNS prophylaxis are discussed, and in particular, the role of cranial radiotherapy and i.t. Ara-C. We conclude that prophylactic CNS therapy may cause cognitive dysfunctions.

Adolescent↗

PubMed2006

Small-world networks and disturbed functional connectivity in schizophrenia.

Disturbances in "functional connectivity" have been proposed as a major pathophysiological mechanism for schizophrenia, and in particular, for cognitive disorganization. Detection and estimation of these disturbances would be of clinical interest. Here we characterize the spatial pattern of functional connectivity by computing the "synchronization likelihood" (SL) of EEG at rest and during performance of a 2Back working memory task using letters of the alphabet presented on a PC screen in subjects with schizophrenia and healthy controls. The spatial patterns of functional connectivity were then characterized with graph theoretical measures to test whether a disruption of an optimal spatial pattern ("small-world") of the functional connectivity network underlies schizophrenia. Twenty stabilized patients with schizophrenia, who were able to work, and 20 healthy controls participated in the study. During the working memory (WM) task healthy subjects exhibited small-world properties (a combination of local clustering and high overall integration of the functional networks) in the alpha, beta and gamma bands. These properties were not present in the schizophrenia group. These findings are in accordance with a partially inadequate organization of neuronal networks in subjects with schizophrenia. This method could be helpful for diagnosis and evaluation of the severity of the disease, as well as understanding the pathophysiologic mechanisms underlying cognitive dysfunction in schizophrenia.

Adult↗

PubMed1987

A visual recognition memory test for the assessment of cognitive function in aging and dementia.

Young, non-demented elderly, and elderly demented subjects were administered a computerized visual recognition memory task. In the task, subjects were instructed to point out the new object from a group of objects whose number was progressively incremented. The test was subject-paced and made use of face-valid stimulus materials; it is closely comparable to tests developed for memory assessment in non-human primates that are sensitive to the effects of hippocampal ablation. The present task was found to elicit significant differences in performance between young and non-demented aged subjects, between the non-demented and demented elderly, and between demented subjects in the early and more advanced stages of senile dementia of the Alzheimer type (SDAT). In a discriminant analysis, the visual recognition memory test scores correctly classified 72.6% of the aged subjects and early SDAT patients. No significant difference in task performance was found between SDAT patients and demented patients with a significant cerebrovascular etiological component. Thus, although the task does not appear to be suitable for diagnostic purposes it would be useful for the assessment of treatment effects upon age-related cognitive dysfunction.

Adolescent↗

PubMed2006

Impaired cognitive performance in asymptomatic peripheral arterial disease: relation to C-reactive protein and D-dimer levels.

BACKGROUND AND PURPOSE: asymptomatic peripheral arterial disease (APAD), a highly prevalent condition in the general older population, is associated with an increased risk of cerebrovascular events because of co-existing clinical or subclinical cerebral atherosclerosis. The purpose of this study was to investigate whether cognitive function is impaired in stroke- and transient ischaemic attack-free patients with APAD, and whether inflammatory and haemostatic markers are associated independently with neuropsychological performance. METHODS: cognitive performances of 164 well-functioning, community-dwelling patients with APAD were compared with those of 164 age-, gender- and education-matched healthy control subjects on six neuropsychological tests. Levels of C-reactive protein (CRP), D-dimer and fibrinogen were also analysed in all participants. RESULTS: patients with APAD scored significantly worse (P < 0.0001) than control subjects on five cognitive tests assessing domains of verbal working memory, attention, perceptuomotor speed, mental flexibility, visuoconstructive skills and visual memory. Multiple linear regression analyses showed that CRP and D-dimer were significant, independent predictors of poorer performances on four and three cognitive tests, respectively, within patients with APAD. CONCLUSIONS: patients with APAD show cognitive impairment in a range of psychometric tests, and CRP and D-dimer appear to be independent negative predictors of some cognitive performances. These findings suggest the need for screening for APAD among at-risk subjects in order to identify patients to be treated for prevention of functional decline and dementia. They also support the hypothesis that inflammation and hypercoagulability are implicated in the pathophysiology of cognitive dysfunction associated with APAD.

Aged↗

PubMed2006

Benign multiple sclerosis.

A small fraction of patients with multiple sclerosis (MS) have a benign course of the disease. The definition of benign MS has been heavily weighted towards physical disability and in particular ambulation. However, patients who are fully ambulatory may still be heavily disabled by non-motor symptoms like fatigue, pain, depression and cognitive dysfunction. These non-motor symptoms should be considered when defining benign MS.

Cognition Disorders↗

PubMed2001

Dementia severity and pattern of cognitive performance in vascular dementia.

We evaluated the influence of dementia severity on cognitive performance in two groups of individuals with vascular dementia (VaD). Performance on the Mini-Mental State Exam (MMSE) was used to determine dementia severity. Tests of executive function, psychomotor speed, memory, language, and visuospatial function were administered. As expected, individuals with severe VaD (MMSE < 18) performed significantly more poorly than individuals with mild VaD (MMSE > or = 18) on most tests. More important, deficits were evident for both groups in each cognitive domain when compared to normative data. These results indicate that multiple cognitive domains are affected even in mild cases of VaD. Clinicians should be aware that although the presence of "patchy" cognitive deficits may indicate stroke, general cognitive dysfunction may occur in mild cases of VaD.

Aged↗

PubMed2004

The impact of cognitive impairment on the rehabilitation process in geriatrics.

A study has been carried out in our geriatric rehabilitation wards, to know better the role of cognitive dysfunction in treatment outcome and processing, mainly functional recovery and comorbidity. We analyzed 478 frail inpatients, 2/3 of them were females, aged 78.7 + 9.2 years, consecutively admitted to the unit. Assessment of cognitive function was performed by the mini mental state examination (MMSE), of functional status by Barthel index (BI), of co-morbidity by cumulative illness rating scale (CIRS) both at the admission and discharge for each patient, together with the usual clinical parameters and social outcome. More than one people in three lived alone and showed some communication problems; one in seven needed modifications in food preparation or nutritional system;more than one in five had pressure sore >/= 2 (EPUAP = European Pressure Ulcers Advisory Panel classification). The mean (+/- SD) levels of the admitted were: MMSE = 20 +/- 7.2; BI total score = 45.5 +/- 28.9; CIRS class = 4 +/- 2, CIRS severity score = 1.9 +/- 0.4. Of the patients, 74.5% were discharged to home. Mean functional gain was 20 points at BI: 65.6 +/-30.7; MMSE improved to 21.6 +/- 7.1 (p = 0.00005 for both comparisons, by Wilcoxon test).MMSE was positively correlated to BI (r = 0.6, p = 0.0005) and negatively correlated (p =0.0005) to CIRS comorbidity (r = -0.33) and severity (r = -0.26), and to age (r = -0.38, p =0.0005) both at admission and at discharge. MMSE at admission was correlated neither to functional gain, nor to improvement of clinical indicators, nor to measures of functional and clinical efficiency. MMSE at discharge showed similar results. In a stepwise multiple correlation analysis, taking the gain in BI as the dependent variable, while BI, serum albumin level, MMSE, CIRS severity and comorbidity indexes at admission as independent variables, MMSE together with BI admission total score and CIRS severity index retained a strong association with functional gain, whilst admission serum albumin levels and CIRSindex lost it. Consistently with some literary data, we showed the actual possibility of functional and clinical gains for people cared in a geriatric rehabilitation ward, all through a wide range of MMSE score, including subnormal scores. Poor cognitive status bears heavily on frailty, but does not hamper the outcomes of genuine rehabilitative efforts in geriatrics.

Aged↗

PubMed2004

Sleep disturbances in elderly: a subjective evaluation over 65.

Sleep in elderly people shows progressive changes caused by general aging processes. Several alterations are described in medical literature: changes of sleep/wake rhythm and modifications both in sleep duration and in sleep architecture. The aim of our study was to evaluate sleep disturbances in elderly people, with and without cognitive impairment,through a sleep questionnaire. Our population included 1000 subjects, over 65 years of age, stratified by sex and age. The first 600 interviews were included in this report. All patients underwent a mini mental state examination (MMSE) and a questionnaire concerning excessive daytime sleepiness. In our total sample, we found a high prevalence of excessive daytime sleepiness, insomnia, nighttime awakenings, snoring, restlessness and periodic leg movements during sleep. Patients with cognitive dysfunctions showed less difficulty in falling asleep and fewer nighttime awakenings; they snored less frequently and were the only ones to present enuresis and to fall off the bed. Moreover, patients with cognitive impairment presented excessive daytime sleepiness with variable intensity and frequency. In conclusion, our results indicate significant differences in sleep disorders between healthy subjects and patients cognitively impaired. Besides, our subjective evaluation seems to be a useful method to perform an assessment of sleep disturbances in elderly people.

Aged↗

PubMed2004

Movement and motor development in ELBW infants at 1 year is related to cognitive and motor abilities at 4 years.

A relationship between motor ability and cognitive performance has been previously reported. This study aimed to investigate the association between movement and cognitive performance at 1 and 4 years corrected age of children born less than 1000 g, and whether developmental testing of movement at 1 year is predictive of cognitive performance at 4 years. Motor development was assessed at both ages using the neurosensory motor developmental assessment (NSMDA) and motor development was classified as normal, or minimal, mild, moderate-severe dysfunction. Cognitive performance was assessed on the Griffith Mental Developmental Scale at 1 year and McCarthy Scales of Children's Abilities at 4 years. Subjects included 198 children of birthweight less than 1000 g. Of these 132 children returned for follow-up at the corrected ages of both 1 and 4 years. The 66 children not included had a slight increase in gestational age, while the mothers were younger and had a lower level of education. A significant association was found between NSMDA group classification at 1 year and cognitive performance at both 1 and 4 years (p<0.001; p<0.0001) and between the subscales of each test (1 year, p<0.0001; 4 years, p<0.001). Group classification of motor development at 1 year was predictive of cognitive performance at 4 years (p<0.0001) and this was independent of biological and social factors and presence of cerebral palsy (CP). The findings support a close link between motor and cognitive development in children born <1000 g and emphasise the advantage of detailed assessment of movement at 1 year.

Child Development↗