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Cognitive correlates of human brain aging: a quantitative magnetic resonance imaging investigation.

The relations between age-related changes in brain structure and neuropsychological test performance in 320 elderly nonclinical volunteers (ages 66-90) were examined by using quantitative MRI data and measures of attention, information processing speed, language, memory, and visuospatial ability. Final path analyses revealed significant brain-behavior relationships for two of the six cognitive measures: the Trail Making Test part B and visual delayed memory. Poorer performance on Trails B was associated with smaller cerebral hemisphere volumes and larger volumes of peripheral CSF, lateral ventricles, and third ventricle. Poorer recall on visual delayed memory was associated with larger volumes of the lateral ventricles and third ventricle. The findings demonstrate a relationship between age-related changes in brain structure and an age-related decline in attention, psychomotor speed, and visual delayed memory. The neurobiological basis for this relationship requires further investigation.

Aged↗

Verbal learning and visuomotor attention in Alzheimer's disease and geriatric depression.

We compared the verbal learning and visuomotor attention of 34 Alzheimer's patients and 18 depressive patients. Verbal learning was assessed using The Hopkins Verbal Learning Test--Revised (HVLT--R); visuomotor attention was assessed using the Trail Making Test (TMT). The Alzheimer's patients had significantly lower scores on immediate and delayed recall of a word list. There was a nonsignificant trend in this group toward a fewer number of true positives and a greater number of false positives. Alzheimer's patients were significantly slower on Trails A, with a nonsignificant trend toward slower performance on Trails B. No difference was observed in accuracy of attentional processing. The results are discussed in terms of other factors, such as stage of cognitive decline, which might have influenced the findings.

Aged↗

Systemic oxidative stress and cognitive performance in the population-based EVA study. Etude du Vieillissement Artériel.

The aim of this study was to examine the relationships between cognitive functioning and blood levels of antioxidants and lipoperoxidation products in an elderly population. In 1991-1992, 1389 volunteers (574 men and 815 women aged 59 to 71 years) were recruited from the general population. Levels of selenium, carotenoids, and thiobarbituric-reactive substances in plasma and of vitamin E, glutathione peroxidase, and Cu-Zn superoxide dismutase in red blood cells were measured. Cognitive functioning was assessed with various psychometric tests. We used logistic regression to estimate the risk of poor cognitive functioning (< 25th percentile of the score distribution) associated with low values of each antioxidants (< 25th percentile) including potential confounding factors. A low level of total carotenoids (< 1.86 mumol/l) was associated with poor cognitive performance in two tests assessing visual attention and logical reasoning: the Trail-Making Test part B [OR = 1.34 IC95% (0.99-1.81), p = .055] and the Digit Symbol Substitution from the WAIS-R [OR = 1.38 IC95% (1.02-1.89), p = .04]. Low levels of other antioxidants and high levels of thiobarbituric-reactive substances were not related to poor cognitive functioning. Results observed with plasma carotenoids are in accordance with previous data obtained mostly from dietary records.

Aged↗

The subcortical dysfunction hypothesis of memory deficits in depression: neuropsychological validation in a subgroup of patients.

The subcortical dysfunction hypothesis of verbal learning and memory deficits in depression was evaluated by comparing the memory test profiles of unipolar depressives (n = 40) and bipolar depressives (n = 9) with those of patients with a prototypical subcortical dementia (Huntington's disease, HD), patients with a prototypical cortical dementia (Alzheimer's disease, AD), and normal controls. In a discriminant function analysis that well-differentiated the HD, AD, and normal subjects, it was found that 28.6% of the depressed patients were classified as HD patients (DEP-HD subjects), 49.0% were classified as normals (DEP-N subjects), none were classified as AD patients, and 22.4% were not well-classified. The DEP-HD group closely resembled the HD group on additional indices of verbal learning and memory, and differed from the DEP-N group, which strongly resembled the normal control group. DEP-N patients also performed significantly better than DEP-HD patients on a number of other neuropsychological tests (e.g., WAIS-R Digit Symbol, category fluency, Trail Making Test Part B). The findings provide support for the subcortical dysfunction hypothesis, but only for a subgroup of depressed patients. Implications for differentiating depressive "pseudodementia" from AD are discussed.

Adult↗

Effects of treatment for isolated systolic hypertension on cognitive status and depression in the elderly.

The Systolic Hypertension in the Elderly Program (SHEP) was designed as a feasibility study and in part dealt with the effects of the treatment of isolated systolic hypertension on cognitive status and depression. Subjects were 60 years of age or older with a systolic blood pressure of 160 mmHg or greater and diastolic of less than 90 mmHg; free of several specified illnesses or chronic conditions. These volunteers were randomly assigned to treatment (n = 443) and placebo (n = 108) groups. The behavioral assessments at baseline and 1 year later were the SHORT-CARE instrument for depression, cognitive impairment, and disability and other tests of cognitive status (Digit Symbol Substitution and the Trail Making tests). Although the treatment regime was highly successful in controlling the hypertension, it did not have a significant impact on changes in cognitive function or level of depression; a behavioral benefit was not evident but the results are consistent with the view that an effective treatment regime for isolated systolic hypertension in the elderly can be behaviorally safe.

Aged↗

Do older drivers with visual and cognitive impairments drive less?

OBJECTIVE: To determine whether older drivers with poorer cognitive and/or visual function drive fewer miles or avoid driving in situations that pose higher crash risks, such as at nighttime, in rush hour traffic, or when weather conditions are bad. DESIGN: A cross-sectional data analysis conducted as part of a larger prospective study. SUBJECTS: A total of 3238 drivers aged 65 and older applying for renewal of their driver's license at one of eight participating North Carolina driver's license offices. MEASUREMENTS: Subjects were administered a battery of brief tests of cognitive and visual function, which included the Trail Making Test Parts A and B, the Short Blessed Orientation-Memory-Concentration test, and measures of high and low contrast visual acuity, contrast sensitivity, and peripheral vision. Participants were also asked to complete a brief driving survey containing questions about the number of miles they drove and whether they avoided driving under certain conditions, such as after dark or on busy, multi-lane roadways. Driver age and gender were covariates in the analyses. RESULTS: Results of multivariate logistic regression models show a clear pattern of reduced driving exposure--lower annual miles and greater avoidance of high-risk driving situations--associated with lower levels of cognitive and visual function. In general, the prevalence odds of reduced driving exposure were higher for the cognitive function variables than for the visual function variables, and higher for males than for females. Men who scored in the lowest quartile of performance on one of the cognitive tests were six to seven times more likely to report driving fewer than 3000 miles a year than were men scoring in the highest quartile, and women with low scores were one-and-one-half to two times more likely to report driving less than 3000 miles than women with higher scores. CONCLUSIONS: While the findings of this study are reassuring, they do not guarantee that all drivers with cognitive and visual impairments are limiting their driving exposure appropriately, and geriatricians and other health professionals should be encouraged to evaluate their patients' cognitive and visual fitness for driving and provide counsel where indicated.

Aged↗

Dimensions of executive function in Parkinson's disease.

BACKGROUND: Executive impairment is common in Parkinson's disease (PD). However, it is unknown which dimensions of executive function are assessed by commonly used neuropsychological instruments and if clinical correlates of specific dimensions exist. METHOD: A convenience sample of 46 PD patients was evaluated with three executive function tests: the Tower of London-Drexel, the Trail-Making Test and the Stroop Color-Word Test. Factor analysis was used to probe for dimensions of executive control, and linear regression models were used to explore the association between the generated factors and other clinical features. RESULTS: Factor analysis revealed two executive factors, one related to planning (eigenvalue=4.2) and the other to inhibitory control (eigenvalue=1.8), together accounting for 75% of the variance in scores. In linear regression models, poorer planning was associated with increasing severity of apathy (t=2.11, p=0.041), and diminished inhibitory control was associated with increasing severity of parkinsonism (t=2.78, p=0.008) and lower educational level (t=-2.23, p=0.032). CONCLUSIONS: Planning deficits and diminished inhibitory control are two dimensions of executive impairment in PD, the former associated with decreased motivation and the latter with increased motor slowing. Similar performance on both executive and non-executive components of these instruments suggests that results of executive testing in PD may be confounded by non-executive deficits.

Adult↗

Chronic deep brain stimulation of the subthalamic nucleus for Parkinson's disease: effects on cognition, mood, anxiety and personality traits.

OBJECTIVE: To evaluate modifications occurring in cognitive functions and behavioural aspects in a group of 72 consecutive patients with Parkinson's disease (PD) 15 months after bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). METHODS: 72 consecutive PD patients bilaterally implanted for DBS of the STN were evaluated before and after surgery with a mean follow-up of 15 months. A neuropsychological assessment was performed to evaluate reasoning (Raven Colour Matrices), memory (Bisyllabic Word Repetition Test, Corsi's Block-Tapping Test, Paired-Associate Learning) and frontal executive functions (Trail Making Test Part B, Nelson Modified Card Sorting Test, phonemic and category verbal fluency tasks). Mood and suicidal ideation were evaluated using the Beck Depression Inventory (BDI). Anxiety was measured by means of the State-Trait Anxiety Inventory and personality traits were evaluated with the Structured Clinical Interview for the DSM-III-R Axis II Disorders (SCID-II). Assessment of thought disorders and apathy was based on subitems of the Unified Parkinson's Disease Rating Scale. RESULTS: The comparisons between pre- and postoperative neuropsychological test scores showed a significant worsening only in phonemic and semantic verbal fluency tasks, while fewer errors were found in the Nelson Modified Card Sorting Test. Globally, behavioural assessment evidenced a small improvement in mood, as assessed by the BDI, in obsessive-compulsive and paranoid personality traits (SCID-II). Thought disorders worsened while suicidal ideation, anxiety and apathy showed no postoperative modifications. The analysis of individual outcomes (+/-1 SD criterion) evidenced a relevant postoperative cognitive decline in 3 patients out of 65 (4.5%). Moreover, following implantation, 1 patients exhibited psychosis (1.5%), 2 patients experienced a clinically relevant worsening of depressive symptoms (3%), 7 patients showed an increase in anxiety (12%) and 3 patients a worsening in depression and anxiety symptoms (3%). On the contrary, 12 patients (20%) showed a relevant improvement in mood and 14 patients (23%) a relevant reduction of anxiety symptoms after the surgery. CONCLUSIONS: The present study confirms that STN DBS is cognitively safe since the only relevant change observed was a mild decrease in verbal fluency tasks. Globally, a small postoperative improvement was found in the BDI, and in two SCID-II subscales concerning obsessive-compulsive and paranoid personality traits, even though postoperative behavioural disturbances can occur in individual patients.

Affect↗

Neurobehavioral function and tibial and chelatable lead levels in 543 former organolead workers.

OBJECTIVE: To evaluate the associations between tibial lead, dimercaptosuccinic acid (DMSA)-chelatable lead, and neurobehavioral function in former organolead manufacturing workers with past exposure to organic and inorganic lead. METHODS: Data were collected from 543 subjects with a mean age of 58 years and an average of 17.8 years since last lead exposure. Years since last exposure to lead was used to estimate tibial lead levels in the year of last occupational lead exposure, termed "peak tibial lead." Current tibial lead levels, measured by x-ray fluorescence, were extrapolated back using a clearance half-time of lead in tibia of 27 years, assuming first-order clearance from tibia. RESULTS: Peak tibial lead levels ranged from -2.2 to 105.9 microg Pb/g bone mineral, and DMSA-chelatable lead levels were between 1.2 and 136 microg. After adjustment for confounding variables, peak tibial lead was a significant negative predictor of performance on the Wechsler Adult Intelligence Scale-Revised vocabulary subtest (p = 0.02), serial digit learning test (p = 0.04), Rey Auditory-Verbal Learning Test (immediate recall and recognition, p = 0.03 for each), Trail Making Test B (p = 0.03), finger tapping (dominant hand [p = 0.02] and nondominant hand [p < 0.01]), Purdue pegboard (dominant hand, nondominant hand, both hands, and assembly, p < 0.01 for each), and Stroop Test (p < 0.01). Moreover, with one exception, average neurobehavioral test scores were poorer at higher peak tibial lead levels. DMSA-chelatable lead was only significantly associated with choice reaction time (p = 0.01). CONCLUSION: Peak tibial lead was consistently associated with poorer neurobehavioral test scores, particularly in the domains of manual dexterity, executive ability, verbal intelligence, and verbal memory.

Adult↗

Executive functioning in obsessive-compulsive disorder, unipolar depression, and schizophrenia.

The present study investigated whether schizophrenic, unipolar depressive, and obsessive-compulsive psychiatric patients show a distinguishable profile in tasks considered sensitive to frontal lobe functioning. Three psychiatric samples, each comprising 25 patients with little symptomatic overlap, were compared to 70 healthy controls. Participants completed several executive tasks (Wisconsin Card Sorting Test (WCST), verbal fluency, digit span, Stroop, and Trail-Making). Except for age, which was entered as a covariate, subjects did not differ in any sociodemographic background variable. Healthy controls showed superior performance relative to depressive and schizophrenic patients who exhibited comparable deficits in all tasks. Obsessive-compulsive disorder (OCD) patients revealed dysfunctions in the Trail-Making Tests A and B and in the fluency task. Dysfunctions in the domains of working memory, verbal fluency, distractibility, and concept formation were not confined to a specific psychiatric population.

Journal Article↗

Cognitive functions in the informed consent evaluation process: a pilot study.

Assessment of capacity to give informed consent in the general hospital setting usually rests on a clinical judgment made of a patient's understanding and appreciation of his or her illness, a process limited by its subjective nature, interexaminer variability, and relative deficiency of quantitative instruments available to provide collateral information. Inasmuch as identification of associated variables could strengthen this process, this study examines the association of cognitive functions to the capacity to give informed consent. Over a one-year period, 65 patients were evaluated independent of medical or psychiatric diagnoses. The study population consisted of medical and neurology inpatients seen for neuropsychiatric evaluation. All evaluations included assessment of capacity to give informed consent as it related to the reason for the admission to the hospital, followed by administration of the Hopkins Competency Assessment Test, the Mini-Mental Status Examination, the Trail-Making Test, Parts A and B, and the Executive Interview. Of 65 patients, 34 were excluded based on preset criteria. The remaining patients were assigned to either a "competent" or "noncompetent" group based on clinical evaluation. Number of patients, gender, and handedness distributions between groups were similar. The groups did not differ significantly in terms of age or education. Significant between-group differences were found on an empirical measure of competency, a general mental state measure, and on measures of attentional and executive cognitive functions. An analysis of classification rates indicated that a measure of executive cognitive functioning (Executive Interview) had the best sensitivity and specificity in correctly classifying competent and noncompetent patients. The results of this study support the association between the capacity to give informed consent in the hospital setting and measures of cognitive functioning, suggesting that utilization of cognitive function measures may strengthen the competency assessment process.

Adult↗

Measures of memory and information processing in elderly volunteers.

A screening study was carried out in normal elderly volunteers to determine 1. their scores in measures of memory and information processing 2. how the measures correlate with sample characteristics 3. how the measures correlate with each other and with the EEG. We report here on 111 subjects, 56 women and 55 men aged 53-77 years (63.9 +/- 6.8) with average intelligence (Coloured Progressive Matrices CPM 26.7 +/- 5.1). In the C-normed measures of the word list from the Nuremberg Geriatric Inventory (NGI) our sample scored better than average (immediate recall of words C = 7.5, delayed recall of words C = 8.2; mean C = 5). The sample even attained ceiling scores in the test of recognition. The sample likewise had a better than average speed in a color-word test (CWT) of focused attention similar to the Stroop test (e.g., reading C = 7.5, color-naming C = 6.7, interference task C = 6.3) and in the ZVT trail-making test (C = 7.0). In contrast, speed-free focused attention was only average (C = 5.2 and C = 5.5). The following sample characteristics correlated with test measures of memory and information processing (p less than 0.01): age negatively with immediate recall, trail making, incidental episodic memory, focused attention, speed in the CWT; intelligence correlated positively with 10-min adding which relies on working memory (Pauli test) and immediate recall; education correlated positively with delayed recall, visual memory performance in a figures test, immediate recall, and reading speed in the CWT; occupation correlated positively with figures test performance; exercise of profession correlated positively with incidental episodic memory and immediate recall. Age and occupation correlated more with motor measures than with cognitive measures (pegboard, 1 min tapping at maximal speed). Sex had no bearing on memory characteristics, but did on tracking (men better) and color-naming performance in the CWT (women better). Of the semiluxuries, only regular alcohol consumption showed a relationship with the test measures (negatively with color-naming speed, immediate recall, and pegboard performance). Analysis of memory and information processing measures revealed no correlations (r greater than or equal to 0.40) between memory measures from the word list, Pauli test, figures test, and learning. Measures of the CWT correlated with Pauli test and pegboard. ZVT score was the variable with the most correlations (CWT, Pauli test, pegboard). A factor analysis with a reduced set of variables should further clarify the inner structure of our subject's performance.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Italian neuropsychological instruments to assess memory, attention and frontal functions for developmental age.

In this study, a series of tests exploring long-term verbal memory (the Short Story Test), attention (a modified version of Attentional Matrices and the Trail Making Test) and frontal functions (a modified version of the Frontal Assessment Battery) have been standardised on an Italian population of 283 children aged 5-14. Raw scores for each test have been adjusted for a series of variables (child's age, years of parents' education, handedness, gender) and transformed in equivalent scores enabling direct comparison across measures. This study was promoted by LICE (the Italian League Against Epilepsy) in order to provide Italian instruments standardised on the developmental age population and to study some of the most frequently impaired cognitive functions in epilepsy.

Adolescent↗

Action of the benzodiazepine antagonist Ro 15-1788 in humans after sleep withdrawal.

Subsequent to one night of sleep withdrawal the specific benzodiazepine antagonist Ro 15-1788 was infused to 5 healthy volunteers using a double-blind placebo-controlled cross-over design. Using several standardized psychological tests (viso-motor tracking task, complex choice reaction time, trail making test, visual attention and concentration), no performance-improving effects of Ro 15-1788 could be demonstrated. The results are discussed regarding the possible existence of endogenous benzodiazepine ligands.

Adult↗

Neuropsychological profile in patients with obsessive-compulsive disorder over a period of 4-month treatment.

This study investigated the changes of the neuropsychological functions over a 4-month period of treatment in patients with obsessive-compulsive disorder (OCD). Thirty-nine OCD patients and 31 healthy controls were evaluated with neuropsychological and clinical tests. The same tests were readministered 4-months after pharmacological treatment for the OCD patients. At the first series of tests, compared to the controls, the OCD patients were significantly impaired on the immediate and delayed recall of Rey-Osterrieth Complex Figure Test (RCFT), and on the letter and category of Controlled Oral Word Association Test (COWA). They also showed a prolonged response time on Trail Making Test (TMT), part A. The severity of OCD measured by Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) correlated well with the performance on the immediate and delayed recall of RCFT and the response time on TMT, part A. After 4-months' follow-up, the OCD patients still showed impairment on the immediate and delayed recall of RCFT and COWA category. This is despite the fact that they had improved significantly on these functions in comparison with the controls over the period of treatment. In addition, an association between OCD symptoms and the performance on the neuropsychological tests was not observed. The neuropsychological profile of the OCD patients found in the present study is consistent with current theories proposing that the frontal-striatal system is the possible pathophysiological mechanism underlying the development of OCD.

Adult↗

The role of carotid stenosis in vascular cognitive impairment.

As the contribution of carotid stenosis to cognitive impairment still remains unclear, neuropsychological function and soft neurological signs were examined in patients aged 65 and over. Twenty-five patients with symptomatic carotid stenosis (CS) of 75% or more were compared with 25 patients with first anterior circulation stroke, 25 with peripheral vascular disease and 25 healthy controls. All patients were assessed using CAMCOG (Cambridge Cognitive Examination), tests examining frontal lobe function (Behavioural Dyscontrol Scale [BDYS], Trail-Making Tests A and B, Controlled Word Association Test) and a scale for primitive reflexes (Frontal Release Signs Scale). Patients with symptomatic CS showed greater global impairment on CAMCOG and more severe impairment in frontal lobe function than controls. Those patients scoring less than 15 on the BDYS were more likely to have experienced transient ischemic attacks (TIA) for 5 or more years. Frontal lobe dysfunction, suicidal thinking and age were all independent predictors of global cognitive impairment. Mean number of frontal release signs was higher in patients with CS than in controls, with a higher proportion of patients showing all release signs except glabellar, paratonia and snout reflexes. The study is limited by small numbers and the absence of brain imaging, but provides some evidence for an association between severe carotid stenosis and neuropsychological impairment. The presence of clinically 'silent' cerebrovascular disease affecting frontal lobe function may be missed in routine clinical practice.

Aged↗

Surgery of the thoracic aorta using deep hypothermic total circulatory arrest. Are there neurological consequences other than frank cerebral defects?

OBJECTIVE: Deep hypothermic total circulatory arrest has reduced primary morbidity and mortality in thoracic aortic surgery. Although frank neurological deficits have been proven to be a rare complication of this technique, the rate of subtle but irreversible neuropsychological disorders remains unknown. METHODS: A total of 23 patients (15 male, 8 female) who had undergone surgery for dissection or aneurysm of the thoracic aorta using deep hypothermic total circulatory arrest (mean 25.5 min, range 10-75 min) were studied retrospectively. The mean follow-up was 17 months. The following psychometric tests were conducted: a computer-based test battery to assess tonic alertness and sustained attention, the trail making test (TMT part A and B), the Münchner Gedächtnistest and a verbal learning test. In addition, a cerebral dopamine D2 receptor scintigraphy (using the SPECT technique) was performed. For comparison, 10 healthy subjects were studied. RESULTS: With regard to tonic alertness, 69.6 and 30.4% were below the 50th and 10th centiles, respectively, according to age- and education-corrected standard values. The impairment in sustained attention correlated significantly with the duration of the circulatory arrest. On the tests assessing short-term memory, the patients scored 30% below their age- and education-corrected peers. In terms of long-term memory, 60.9 and 39.1% of the patients were below one and two standard deviations, respectively. Concerning speed of information processing whilst 78.3% of the patients were below the 50th and 21.7% below the 10th centile. Indicative of some persistent and functional brain alteration, the dopamine D2 receptor binding was significantly reduced when compared with healthy subjects. CONCLUSIONS: These data prove a substantial and chronic reduction of higher cognitive function in some of the patients who underwent cardiac surgery using deep hypothermic total circulatory arrest; this was accompanied by a depression of the cerebral dopamine D2 receptor binding.

Adult↗

Neuropsychological findings in high-functioning men with infantile autism, residual state.

Ten men (ages 18-39) with clear histories of Infantile autism and approximately average verbal and nonverbal intelligence were studied with a comprehensive battery of neuropsychological tests. Comparisons with 10 matched normal controls showed no significant differences in many visuoperceptual or memory skills or in sensory-perceptual or motor skills or their lateralization. Differences seen on language measures were small, but statistically significant. In contrast to this, the autistic group demonstrated dramatic deficits on simple and complex, verbal and nonverbal problem-solving tasks, such as the Wisconsin Card Sorting Test, selected tasks from the Stanford-Binet, and the Trail Making Test. A left-hemisphere hypothesis of autism was not supported, nor was there compelling evidence of any posterior cortical deficit. Results are compatible with frontal-system dysfunction or with more widespread pathology.

Adolescent↗