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PubMed1988

Human immunodeficiency virus-associated neurobehavioural disorder.

AIDS, ARC, and other HIV-associated diseases were originally conceptualised exclusively in terms of defects in cell-mediated immunity and its consequences. But it is now becoming clear that HIV disease can also be a primary neuropsychiatric disorder, although the precise mechanism by which the retrovirus causes impairment in brain function and, ultimately, structural brain damage, remains obscure. The work presented here indicates another shift in our thinking concerning HIV infection. Until recently it was believed that neurological and neuropsychiatric phenomena tended to occur in the late stages of HIV disease. While that might be true for the more severe form of symptomatology that has been termed the AIDS dementia complex, we believe there is at least preliminary evidence that cognitive change can occur earlier in the course of illness, perhaps even in some medically asymptomatic HIV+ individuals. Other investigators have also noted increased neuropsychological abnormality in patients before they developed AIDS or ARC. For example, Janssen et al. found that about half their patients with lymphadenopathy syndrome (LAS) had some neuropsychological test deficits. Durara et al. recently reported on cerebral metabolic rates for glucose in seven HIV+ asymptomatic individuals, compared to 10 HIV- controls. Four of the HIV+ individuals had abnormal asymmetry in frontal and temporal regions suggesting focal reduction in cerebral glucose metabolism. Further indirect evidence that virus can enter the central nervous system early in the course of HIV disease comes from the work of McArthur and associates.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1984

Sequelae of mild closed head injuries.

Thirty-nine minimal to mild closed head injuries without neurological signs were evaluated by a series of clinically available psychometric tests to determine the presence of identifiable intellectual deficits, rate of recovery, and personality or occupational changes. Even minimally head-injured patients suffer measurable cognitive deficits and occupational and behavioral changes.

Adolescent↗
PubMed1975

Neurobehavioral dysfunction in uremia.

To summarize our concepts relating to impaired function of the mind in uremic patients before and during treatment with maintenance dialysis, the emphasis had gradually shifted from the use of "static taxonomy", the diagnostic labels of mental illness, to a more dynamic and sympathetic appreciation that the observed behaviors represent patients' attempts to cope with disease and threats of disability and death, as influenced by varying levels of intelligence, education, cultural conditioning, life experiences and organization of personality defense mechanisms. The dialysis patient is aware that his behavior evokes reciprocal and complicating responses from important people in his environment. These interactions are perceived and conducted by neurochemical mechanisms of the brain which may be impaired in the abnormal chemical environment imposed by renal failure. It is the behaviors we perceive as indicators of disordered nervous mechanisms. Therefore, it is logical that neurobehavioral phenomena should be measured quantitatively in order 1) to estimate objectively the patients' success in achieving the goal of maintenance dialysis treatment, 2) to assess the comparative adequacy of dialysis regimens and 3) to provide objective end-point measures which are relevant to uremia for further investigations of the etiology and pathogenesis of these critically significant uremic manifestations. Our experimental results using ipsitive cognition performance tasks clearly suggest that discrete human performances may be evoked and employed to detect mentational impairments of uremia in quantitative terms, a fundamental step having central relevance to what dialysis does in controlling uremic symptoms.

Attention↗
PubMed2004

Cognitive changes in patients with Huntington's disease (HD) and asymptomatic carriers of the HD mutation--a longitudinal follow-up study.

OBJECTIVE: Objective information about the onset and progression of cognitive impairment in Huntington's disease (HD) is very important in the light of appropriate outcome measures when conducting clinical trials. Therefore, we evaluated the progression of cognitive functions in HD patients and asymptomatic carriers of the HD mutation (AC) over a 2.5-year period. We also sought to detect the earliest markers of cognitive impairment in AC. METHODS: A prospective study comparing HD patients, clinically asymptomatic HD mutation-carriers (AC) and non-carriers (NC). These groups were examined three times during a period of 2.5 years. At baseline the study sample consisted of 49 subjects. Forty-two subjects (19 HD patients, 12 AC and 11 NC) completed three assessments. A battery of neuropsychological tests measuring intelligence, attention, memory, language, visuospatial perception, and executive functions was performed. RESULTS: The performance of HD patients deteriorated on the following cognitive tests: Symbol Digit Modalities Test (SDMT), Stroop Colour and Word, Boston Naming Test (BNT), Object and Space Perception and Trail Making Test-B. Longitudinal comparison of AC and NC revealed that performances on SDMT, Block Span, Digit Span Backwards, Hopkins Verbal Learning Test (learning and delayed recall) and Conditional Associative Learning Test are impaired in AC. CONCLUSIONS: Tasks measuring mainly attention, object and space perception and executive functions adequately assess the progression of HD disease. Other cognitive functions do not significantly deteriorate. Furthermore, problems in attention, working memory, verbal learning, verbal long-term memory and learning of random associations are the earliest cognitive manifestations in AC.

Adult↗
PubMed2006

The effects of blood pressure reduction on cognitive function: a review of effects based on pooled data from clinical trials.

OBJECTIVE: To review systematically and synthesize quantitatively the evidence from completed randomized, controlled trials of blood pressure reduction on cognitive performance. METHODS: MEDLINE, EMBASE and Cochrane databases were searched to identify randomized, controlled trials that measured the effect of blood pressure reduction on cognitive performance. Additional studies were identified by searching bibliographies of retrieved articles and contacting experts in the field. Data were extracted on study quality, blood pressure, performance on cognitive function tests, antihypertensive treatment regimens and the duration of treatment. Studies were reviewed and abstracted independently by two trained researchers. RESULTS: Sixteen studies with 19 501 subjects were identified. Modest reductions in blood pressure (< 5/3 mmHg) in 13 860 subjects were associated with improvements in Mini Mental State Examination score [weighted mean difference (WMD) = 0.19; 95% confidence interval (CI) = 0.19-0.19] and performance on immediate (WMD = 0.62; 95% CI = 0.21-1.02) and delayed (WMD = 0.67; 95% CI = 0.23-1.11) logical memory tasks. However, studies in 2380 subjects that included tests of perceptual processing and learning capacity (trail making test-A, paired associated learning test) showed impaired performance (WMD = -1.12 s; 95% CI = -1.22 to -1.02 and WMD = -0.04; 95% CI = -0.04 to -0.04) on these tests. CONCLUSION: Blood pressure lowering may have a heterogeneous effect on different aspects of cognitive function. Future studies with specific cognitive end-points are needed for greater clarity to guide practice.

Antihypertensive Agents↗
PubMed2002

Improved executive functioning following repetitive transcranial magnetic stimulation.

The cognitive effects of active and sham repetitive transcranial magnetic stimulation (rTMS) were examined in 19 middle-aged and elderly patients with refractory depression. Patients received either active (n = 9) or sham (n = 10) rTMS targeted at the anterior portion of the left middle frontal gyrus. Patients in the active rTMS group improved significantly on a test of cognitive flexibility and conceptual tracking (Trail Making Test-B).

Aged↗
PubMed2004

Executive function in sleep apnea: controlling for attentional capacity in assessing executive attention.

STUDY OBJECTIVES: As the effects of general slowness and decreased attentional capacity on higher executive attention have not been fully taken into account in the sleep apnea literature, we statistically controlled for basic attentional performance in evaluating executive attention per se in sleep apnea patients. DESIGN: A case-controlled design was used with comparison of basic and executive attentional tasks. PARTICIPANTS: Thirty-six polysomnographically diagnosed patients (mean apnea-hypopnea index = 60.5 +/- SD 31.6) participated, together with 32 healthy controls. MEASUREMENTS AND RESULTS: Neuropsychological tests included Trail Making part A and B, Symbol Digit Modalities (SDMT), Digit Span forward and backward, Stroop Color-Word, Five-Point design fluency, and an Attentional Flexibility task. Patients' vigilance data indicated time-on-task decrements after 10 minutes. Moreover, their performance was significantly reduced on the SDMT (effect size d = 0.93), the Digit Span forward task (d = 0.44), the number of errors on the basic 2-choice reaction time subtest of the Attentional Flexibility task (d = 0.74) and the mean RT on the actual Attentional Flexibility subtest (d = 0.54). It has been argued that the latter poor performance was probably primarily related to the task's phonologic loop component of working memory rather than to an attentional switching deficit per se. No other performance differences were found between patients and healthy controls. CONCLUSIONS: In addition to vigilance decrements, attentional capacity deficits clearly emerge, ie, slowed information processing and decreased short-term memory span. However, no specific clinical indications for executive attentional deficits--such as disinhibition, distractibility, perseveration, attentional switching dysfunction, decreased design fluency, or an impaired central executive of working memory--are found in patients with severe sleep apnea. Their cognitive performance seems very similar to the cognitive decline found after sleep loss and qualitatively different from patients with chronic obstructive pulmonary disease, suggesting sleepiness as the primary factor in a parsimonious explanation for the attention deficits in sleep apnea, without the need to assume prefrontal brain damage.

Attention↗
PubMed1980

Tactile sensation--an all-or-none effect of cerebral damage.

Compared the Von Frey Hair scores of 158 brain-damaged Ss and 40 normals to scores on Speech Perception, Block Design and Trail Making B tests, in order to examine the distribution of organically affected tactile sensation. Organic impairment produced an all-or-none distribution pattern on the tactile test in that almost all scores fell either within the normal range or in the severely impaired range. By contrast, scores of the cognitive functions formed a graded continuous distribution. These results are related to Luria's concept of diminishing modality specificity. In addition, the neurological examination evidently is designed to measure all-or-none functions, while the neuropsychological examination is concerned with graded continuous functions.

Adult↗
PubMed2003

Impaired visuomotor integration in acute schizophrenia.

Based on the interaction of eye and hand movements a comprehensive index summarizing schizophrenia patients' difficulties during the performance process in Trail-Making Test-B (TMT-B) was developed. The process of TMT-B performance was modelled as a sequence of planning, acting and resting periods in 23 inpatients with acute schizophrenia, 17 inpatients with acute depression and 21 non-psychiatric controls, each assessed at least twice within four weeks. Transition probabilities between these states were calculated and structured by factor analysis. Throughout their hospital stay schizophrenia patients scored significantly lower than non-patients on a derived "visuo-manumotor integration factor", characterized by high loadings of transitions between planning and acting periods. A significant negative correlation of this factor with performance time revealed frequent alternations between these two states and thus high factor scores to be a prerequisite for good TMT-B performance. No relationship of factor scores with psychopathology and medication could be found. Depressive patients differed neither from non-patients nor from schizophrenia patients during the acute phase of the illness, but scored significantly higher than schizophrenia patients shortly before discharge. Accordingly, poorer TMT-B performance in schizophrenia patients seems related to impaired planning strategies, which might be a nosologically specific, trait-like characteristic, probably related to neural dysfunctions involving the prefrontal cortex.

Acute Disease↗
PubMed2001

Recognition memory and verbal fluency differentiate probable Alzheimer disease from subcortical ischemic vascular dementia.

BACKGROUND: Alzheimer disease (AD) and vascular dementia are among the most frequently occurring causes of dementia in the world, and their accurate differentiation is important because different pharmaceutical strategies may modify the course of each disease. OBJECTIVE: To determine which of 10 neuropsychological test scores can accurately differentiate patients with probable AD from those with subcortical ischemic vascular dementia (SIVD) for use in evidence-based clinical practice. DESIGN: Patients with suspected dementia were referred to the study by family physicians, geriatricians, and neurologists. All participants received a thorough assessment according to standard diagnostic guidelines. Diagnoses of probable AD (n = 31) and probable SIVD (n = 31) were made according to consensus criteria. The diagnosticians were blind to the results of the 10 neuropsychological test scores. RESULTS: There were no significant differences between the groups in age or Mini-Mental State Examination scores. Logistic regression analyses identified 2 neuropsychological tests that best distinguished the groups (sensitivity = 81%; specificity = 84%; positive likelihood ratio = 5.1). These were the recognition memory subtest of the Rey Auditory Verbal Learning Test and the Controlled Oral Word Association Test. The AD group performed better on the oral association test, whereas the SIVD group did better on the recognition memory test. CONCLUSION: Patients with probable AD and probable SIVD can be distinguished with a high degree of accuracy using these 2 neuropsychological tests.

Aged↗
PubMed2002

Hormone replacement therapy to maintain cognitive function in women with dementia.

BACKGROUND: As estrogens have been shown to have several potentially beneficial effects on the central nervous system, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by means of estrogen replacement therapy (ERT) could be protective against cognitive decline and the development of Alzheimer's disease (AD) or other dementia syndromes. OBJECTIVES: To investigate the effects of ERT (estrogens only) or HRT (estrogens combined with a progestagen) compared with placebo in randomized controlled trials (RCTs) on cognitive function of postmenopausal women with dementia. SEARCH STRATEGY: The CDCIG Specialized Register, which contains up-to-date records from many medical databases was searched using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen*, progesteron* and Alzheim* on 16th of May 2002. In addition, MEDLINE (1966-2002/01); EMBASE (1985-2002/01); and PsyINFO (1967-2002/01) were searched. SELECTION CRITERIA: All double-blind randomized controlled trials (RCTs) into the effect of ERT or HRT for cognitive function with a treatment period of at least two weeks in postmenopausal women with AD or other types of dementia. DATA COLLECTION AND ANALYSIS: Abstracts of the references retrieved by the searches were read by two reviewers (EH and KY) independently in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the ensuing lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. The two reviewers also assessed the quality of other aspects of the included trials. One reviewer (EH) extracted the data from the studies, but was aided and checked by JB from Cochrane. MAIN RESULTS: A total of five trials including 210 women with AD were analysed. Meta-analyses showed that there was a limited positive effect from low dosage of conjugated equine estrogens (CEE, 0.625 mg once a day) but not from higher dosage (1.25 mg of CEE once a day) on the Mini-Mental Status Examination after 2 months (WMD=1.28, 95% C.I.=0.26 to 2.30, z=2.45, p<0.01) and the effect disappeared after 3, 6 and 12 months of treatment. This effect was small and not clinically relevant as there was only a difference of 1 point on average in comparison with the placebo users (the scale range is 0-30). There were also short-term effects of 1.25 mg of CEE on tests of concentration and executive function, namely the Trail Making Test-B (WMD=-40.90, 95% C.I.-79.29 to -2.51, z=2.09, p<0.05) and Digit Span backward (WMD=0.67, 95% C.I.=-0.01 to 1.34, z=1.94, p<0.05). With regard to memory, only cued delayed recall of a word list was positively affected by 2 months of transdermal diestradiol (E2) (WMD=6.50, 95% C.I.=4.04 to 8.96, z=5.19, p<0.0001). No HRT effects were seen on other word lists, Paragraph Recall or Paired Associate Learning. In addition, no effects were seen on visual memory, language functions, most speeded tests, clinical rating scales or depression. Controls had better performance on the delayed recall of the Paragraph Test (overall WMD=-0.45, 95% C.I.=-0.79 to -0.11, z=2.60, p<0.01) after 1 month and on Finger Tapping after 12 months (WMD=-3.90, 95% C.I.=-7.85 to 0.05, z=1.93, p<0.05). Clinicians also gave controls a better score on a dementia rating scale (CDR, overall WMD=0.35, 95% C.I.=0.01 to 0.69, z=1.99, p<0.05). Positive findings in favour of treatment or placebo could have been random effects caused by multiple analyses. After correction for multiple testing, only the short-term positive treatment effect of E2 on memory remained. REVIEWER'S CONCLUSIONS: Currently, HRT or ERT for cognitive improvement or maintenance is not indicated for women with AD. As we did not have data on women with other types of dementia (e.g. vascular dementia) this remains to be investigated. As most studies only used CEE and our earlier review in healthy women found effects only after a bolus injection of E2, it remains possible that different preparations or types of ERT or HRT could have a different effects. Several questions are raised in this review, including whether factors such as age, dementia onset (early AD), or the use of a particular preparation for a longer duration of treatment could have different effects. Perhaps the most important question is whether ERT or HRT can delay the time of onset of dementia. For answers to these questions, we have to await the results of the large RCTs currently in progress in the UK, USA, and Canada.

Cognition↗
PubMed2005

Breath ammonia testing for diagnosis of hepatic encephalopathy.

Measurement of arterial ammonia has been used as a diagnostic test for hepatic encephalopathy, but obtaining an arterial specimen is an invasive procedure. The aim of this study was to evaluate the ability of a minimally invasive, highly sensitive optical sensing device to detect ammonia in the breath of patients with end-stage liver disease and to evaluate the correlation of breath ammonia levels, arterial ammonia levels, and psychometric testing. Fifteen subjects with liver cirrhosis and clinical evidence of hepatic encephalopathy underwent mini-mental status examination, number connection test, focused neurological examination, and arterial ammonia testing. On the same day, breath ammonia testing was performed using an apparatus that consists of a sensor (a thin membrane embedded with a pH-sensitive dye) attached to a fiberoptic apparatus that detects optical absorption. Helicobacter pylori testing was performed using the 14C urea breath test. A positive correlation was found between arterial ammonia level and time to complete the number connection test (r = 0.31, P = 0.03). However, a negative correlation was found between breath ammonia level and number connection testing (r = -0.55, P = 0.03). Furthermore, no correlation was found between breath and arterial ammonia levels (r = -0.005, P = 0.98). There is a significant correlation between the trailmaking test and arterial ammonia levels in patients with cirrhosis. However, no correlation was found between breath and arterial ammonia levels using the fiberoptic ammonia sensor apparatus in this small study.

Ammonia↗
PubMed2002

Differential rates of regional brain change in callosal and ventricular size: a 4-year longitudinal MRI study of elderly men.

Brain structure changes in size with normal aging, but the rate at which different structures change is controversial. We used magnetic resonance imaging (MRI) performed twice, 4 years apart, to compare rates of age-related size change of the corpus callosum, which has been inconsistently observed to thin with age, with change in the lateral ventricles, which are well established to enlarge. Subjects were 215 community dwelling, elderly men (70-82 years old at initial MRI), who were participants in a longitudinal study of cardiovascular risk factors. Percent change in size was significant for both the callosal and ventricular measures, but annual rate of ventricular expansion (2.9%) was significantly greater than annual rate of callosal thinning (-0.9%). Callosal regions showed statistically equivalent rates of shrinkage; ventricular dilatation was symmetrical. Neither callosal and ventricular rates of change correlated with each other (r = 0.01), nor did genu and splenium rates of change correlate with each other (r = 0.05). Tests of speeded processing were administered contemporaneously with both MRIs to examine functional ramifications of observed brain changes. Decline in the Mini-Mental State Examination was related to thinning of the splenium, and decline in Stroop test word reading was selectively related to thinning of the callosal body. These longitudinal data support the contentions that differential rates of change occur in different brain regions in normal aging, age-related callosal thinning contributes to functional declines, and rate of change in one region can be independent of rate of change in another region, even within a brain structure.

Aged↗