Cystatin C as a marker of cognitive function in elders: findings from the health ABC study

We determined whether serum cystatin C, a novel measure of kidney function that colocalizes with brain beta-amyloid, is associated with cognition among 3,030 elders. Those with high cystatin C (n = 445; 15%) had worse baseline scores on Modified Mini-Mental State Examination or Digit Symbol Substitution Test (p or=1.0 standard deviation) was greatest among those with high cystatin C (Modified Mini-Mental State Examination: 38 vs 25%; adjusted odds ratio, 1.92; 95% confidence interval, 1.37-2.69; Digit Symbol Substitution: 38 vs 26%; odds ratio, 1.54; 95% confidence interval, 1.10-2.15).     

Normative Data on Neuropsychological Tests for Very Old Adults Living in Retirement Villages and Hostels

Normative data on neuropsychological tests for very old adults living in retirement villages and hostels are under-represented in the literature. This study reports normative data on the Mini-Mental State Examination, Digit Span Forwards, Digit Span Backwards, the Digit Symbol Substitution Test, the Controlled Oral Word Association Test, the Stroop Neuropsychological Screening Test and the National Adult Reading Test. Age and education showed moderate correlations with neuropsychological test performance. For all tests except the Stroop, differences between residents of retirement villages and hostels were explained by age and education. Men performed better on the NART than women, but this difference was eliminated when education was controlled for statistically.     

Normative data on neuropsychological tests for very old adults living in retirement villages and hostels

Normative data on neuropsychological tests for very old adults living in retirement villages and hostels are under-represented in the literature. This study reports normative data on the Mini-Mental State Examination, Digit Span Forwards, Digit Span Backwards, the Digit Symbol Substitution Test, the Controlled Oral Word Association Test, the Stroop Neuropsychological Screening Test and the National Adult Reading Test. Age and education showed moderate correlations with neuropsychological test performance. For all tests except the Stroop, differences between residents of retirement villages and hostels were explained by age and education. Men performed better on the NART than women, but this difference was eliminated when education was controlled for statistically.     

Mild head injury and speed of information processing: A prospective study of professional rugby league players

Abstract

The sensitivity of several short tests of speed of information processing to the effects of mild head injury in rugby league football was investigated. The measures used were the Symbol Digit Modalities Test, the Digit Symbol Substitution Test, and the Speed of Comprehension Test. Two studies were conducted, the first to examine the effect of practice, the second to determine sensitivity to cognitive impairment immediately following injury. The first study established alternate form equivalence and demonstrated that performance on the Speed of Comprehension and Digit Symbol Substitution tests improved with practice, whereas the Symbol Digit Modalities test remained stable. A second study of 10 players who subsequently sustained mild head injuries showed that measures of speed of information processing were sensitive to impairment in the postacute phase, whereas an untimed task of word recognition (Spot-the-Word) was not. Speed of Comprehension was more sensitive to postinjury impairment than either the Digit Symbol Substitution or Symbol Digit Modalities tests. A repeated baseline assessment before injury using the higher score to reflect a player's potential, allowed measurement of impaired performance on sensitive tests.     

Depressive symptoms and cognitive decline in nondemented elderly women: a prospective study

BACKGROUND: The association between depressive disorders and subsequent cognitive decline is controversial. We tested the hypothesis that elderly women (aged 65 years and older) without dementia but with depressive symptoms have worse cognitive function and greater cognitive decline than women with few or no symptoms. METHODS: As part of an ongoing prospective study, we evaluated 5781 elderly, mostly white, community-dwelling women. Women completed the Geriatric Depression Scale short form. Three cognitive tests--Trails B, Digit Symbol, and a modified Mini-Mental State Examination--were administered at baseline and approximately 4 years later. Baseline, follow-up, and change scores for the cognitive tests were analyzed by analysis of covariance and Kruskal-Wallis analysis; the odds of cognitive deterioration (> or =3-point decline on the modified Mini-Mental State Examination) were determined by logistic regression. RESULTS: At baseline, 211 (3.6%) of the women had 6 or more depressive symptoms. Only 16 (7.6%) of these women were receiving antidepressant medication. Increasing symptoms of depression were associated with worse performance at baseline and follow-up on all 3 tests of cognitive function (P<.001 for all comparisons). For example, the baseline Digit Symbol score (mean +/- SD) was 45.5 +/- 10.7 among women with 0 to 2 symptoms of depression, 40.3 +/- 10.7 for women with 3 to 5 symptoms, and 39.0 +/- 11.3 for women with 6 or more symptoms. After adjusting for the baseline score, cognitive change scores were also inversely associated with the number of depressive symptoms (P<.001 for all comparisons). Odds ratios for cognitive deterioration using 0 to 2 symptoms as the reference were 1.6 (95% confidence interval, 1.3-2.1) for 3 to 5 symptoms and 2.3 (95% confidence interval, 1.6-3.3) for 6 or more symptoms. Results were similar after being adjusted for education, age, health status, exercise, alcohol use, functional status, and clinic site. CONCLUSIONS: Depressive symptoms in older women are associated with both poor cognitive function and subsequent cognitive decline. Mechanisms underlying the association between these 2 common conditions need further exploration.     

Magnetic resonance imaging predictors of cognition in mild cognitive impairment

OBJECTIVES: To describe magnetic resonance imaging characteristics in a large sample of subjects with mild cognitive impairment (MCI) and to investigate associations between these characteristics and cognition. DESIGN: Cohort study. SETTING: Baseline data of a randomized, double-blind, placebo-controlled clinical trial of galantamine in MCI. PATIENTS: Included in the study were 896 subjects with MCI (age [mean +/- SD], 70 +/- 9 years; 54% women) with available clinical and magnetic resonance imaging data. MAIN OUTCOME MEASURES: Neuropsychology: Alzheimer Disease Assessment Scale, cognitive subscale, MCI version, assessing global cognition; delayed recall on the New York University Paragraph Recall Test, assessing episodic memory; and Digit Symbol Substitution Test, assessing executive function. Neuroimaging: Medial Temporal Lobe Atrophy (MTA) Rating Scale (0-4) and Age-Related White Matter Changes Scale (0-30), assessing white matter hyperintensities (WMHs); and lacune counts. RESULTS: Median MTA score was 2 (range, 0-4), and mean (+/- SD) Age-Related White Matter Changes Scale score 6.0 (+/- 4.7). Lacunes were present in 33% of subjects. In unadjusted models, increasing MTA and WMHs were associated with poorer performance on all cognitive tests, and lacunes with poorer performance on the Alzheimer Disease Assessment Scale, cognitive subscale, MCI version, and the Digit Symbol Substitution Test. In multivariable models, including magnetic resonance imaging measures simultaneously, MTA remained a predictor of cognition, whereas WMH had no independent predictive value. There was an interaction between MTA and lacunes: the strength of the association with the Digit Symbol Substitution Test increased with decreasing MTA. CONCLUSIONS: Medial temporal lobe atrophy seems to be a more important predictor of cognition than small-vessel disease in MCI. Lacunes were associated with performance on the Digit Symbol Substitution Test, especially in subjects with milder MTA. Although WMHs were prevalent and associated with cognition in unadjusted analyses, there was no discernible association between WMHs and the cognitive measures in this study after adjustment for age.     

Test-retest reliability and practice effects of a rapid screen of mild traumatic brain injury

Test-retest reliabilities and practice effects of measures from the Rapid Screen of Concussion (RSC), in addition to the Digit Symbol Substitution Test (Digit Symbol), were examined. Twenty five male participants were tested three times; each testing session scheduled a week apart. The test-retest reliability estimates for most measures were reasonably good, ranging from .79 to .97. An exception was the delayed word recall test, which has had a reliability estimate of .66 for the first retest, and .59 for the second retest. Practice effects were evident from Times 1 to 2 on the sentence comprehension and delayed recall subtests of the RSC, Digit Symbol and a composite score. There was also a practice effect of the same magnitude found from Time 2 to Time 3 on Digit Symbol, delayed recall and the composite score. Statistics on measures for both the first and second retest intervals, with associated practice effects, are presented to enable the calculation of reliable change indices (RCI). The RCI may be used to assess any improvement in cognitive functioning after mild Traumatic Brain Injury.     

Differentiation of cognitive and motor aspects in a digit symbol substitution test in Anorexia nervosa patients, before and after weight restoration

BACKGROUND: In a previous study, using computerized analysis of fine motor behaviour, seriously underweight anorexia nervosa patients in the early phase of treatment were found to have shorter reaction times, but not movement times, in experimental drawing and copying tasks. These differences persisted with weight restoration. SAMPLING AND METHODS: Using computerized analysis of writing and drawing behaviour during the performance of a Digit Symbol Substitution Test, 15 anorexia nervosa patients were compared with 15 normal controls, matched for age, sex and educational level. Patients were retested after weight restoration, as were controls after a similar interval. RESULTS: Patients turned out to be superior in the cognitive, but not in the motor aspects of the Digit Symbol Substitution Test. These differences persisted after weight restoration. A practice effect, due to repeated testing, was found in both groups, which turned out to be cognitive in nature. CONCLUSIONS: The findings show that this new technique can add to the interpretation of classic neuropsychological tests. The results are compatible with previous findings of intact or even superior functioning in anorexia nervosa patients on neuropsychological tasks requiring considerable cognitive effort.     

Subjective memory complaints in an elderly sample: a cross-sectional study

BACKGROUND: Community based studies show that neurological or psychiatric symptoms are very frequent among the elderly population, with poor memory complaints being the most common. However, the relationship between poor memory complaints and objective memory performance is unclear. We designed this study to evaluate whether subjective memory complaints (SMC) are associated with objective cognitive performance or depression amongst the elderly Brazilian generation. METHODS: A cross-sectional study was carried out in 114 patients who were 50+, with or without SMC having no obvious cognitive impairment at its baseline (this was screened by the Mini-Mental State Examination with cut-off values adapted according to the subjects' educational background). Subjects were assessed regarding memory difficulty complaints, demographic data and underwent a neuropsychological assessment made up of nine cognitive tests (Rey Auditory Verbal Learning Test, Visual Reproduction Test, Logic Memory--History A, Free and Cued Selective Reminding Test, Stroop Test, Digit Span, Digit Symbol, Trail Making Test, fluency tests: naming animals and fruits) and the Geriatric Depression Scale. RESULTS: Twenty-one percent of the subjects had subjective memory complaints. The scores in the cognitive assessment of subjects with SMC did not differ from the scores of subjects without SMC. However, patients with subjective memory complaints had lower scores in the fluency test--category animals and the Geriatric Depression Scale. CONCLUSIONS: These results support the finding from other cross-sectional studies showing that subjective memory complaints are associated with depressive symptoms rather than objective cognitive performance.     

Double cross-validation and improved sensitivity of the rapid screen of mild traumatic brain injury

This study aimed to replicate and cross-validate the Rapid Screen of Concussion (RSC) for diagnosing mild TBI (mTBI). One hundred (81 male, 19 female) cases of mTBI and 35 (23 male and 12 female) cases of orthopaedic injuries were tested within 24 hr of injury. Double cross-validation was used to examine whether total RSC scores obtained in the current sample, generalised to one previously reported. In the new sample, mTBI patients answered fewer orientation questions, recalled fewer words on the learning trial and after a delay, judged fewer sentences in 2 min, and completed fewer symbols in the Digit Symbol Substitution Test than orthopaedic controls. The formulae and cut-offs developed on the original and new samples produced similar sensitivity and overall correct classification rates. Inclusion of the Digit Symbol Substitution Test performance of the new sample improved the sensitivity (80.2%) and specificity (82.6%) in males. It did not improve the correct classification rate in females, which was 89.5% sensitivity and 91.7% specificity before the inclusion of the Digit Symbol Substitution Test. Taken together, these results indicate that a combined score on this 12-min screen yields a measure of level of brain impairment up to 24 hr after mTBI.     

Motor dysfunction influence on executive functioning in manifest and premanifest Huntington's disease

Motor disturbances can be present in both manifest and premanifest Huntington's disease (HD). We aimed to investigate the role of motor functioning on executive functioning to better understand the progression of cognitive dysfunction in HD. Forty patients with manifest HD, 21 patients with premanifest HD, and a group of 28 controls were tested twice with a 1‐year interval. For the Symbol Digit Modalities Test and the Figure Fluency Test, extra conditions were designed to measure motor involvement. Subtraction of this motor score from the original test score resulted in isolation of the cognitive component. Groups were compared on motor, cognitive, and original test scores using multilevel regression analysis. Manifest patients had lower baseline scores of 0.53 standard deviations (SD) on the original Symbol Digit Modalities Test (P = 0.03) and 0.71 SD on the motor isolation part (P = 0.006), and they showed a deterioration of 0.47 SD over 1 year of follow‐up on the original Symbol Digit Modalities Test (P = 0.001) compared with controls. Premanifest patients had lower baseline scores of 0.67 SD on the Symbol Digit Modalities motor part (P = 0.008) and deterioration of 0.48 SD on the original (P = 0.001) and cognitive isolation (P = 0.02) parts. Secondary analyses revealed that the premanifest deterioration resulted from the close‐to‐predicted‐onset group. Motor disturbances have a negative influence on performance on the Symbol Digit Modalities Test. Isolation of the cognitive component of this test revealed cognitive deterioration in the premanifest group only, caused by deteriorating scores for patients who were close to their predicted clinical disease onset. The Figure Fluency Test did not prove sensitive to cognitive change. © 2014 International Parkinson and Movement Disorder Society     

Sensorimotor and cognitive slowing in schizophrenia as measured by the Symbol Digit Substitution Test

OBJECTIVES: A vast amount of studies demonstrates the presence of psychomotor slowing in schizophrenia. The objective of the present study was to investigate whether this overall psychomotor slowing can be divided into distinct processes that differentially affect cognitive functioning in schizophrenia. METHODS: The pen-tip movements of 30 schizophrenic inpatients and 30 matched controls were digitally recorded during performance of the Symbol Digit Substitution Test (SDST) and analysed to differentiate matching time and writing time, representing the cognitive and sensorimotor component of slowing, respectively. In addition, the results were compared to each other and to the scores of traditional neuropsychological tests that assess domains such as memory and attention. RESULTS: Both matching time and writing time were longer in the schizophrenic patients relative to the controls but did not correlate. Only matching time correlated significantly with the conventional neuropsychological test results. CONCLUSIONS: Although schizophrenic patients display both sensorimotor and cognitive slowing, the two processes are unrelated. Furthermore, only the cognitive component was associated with most of the cognitive deficits as measured by traditional neuropsychological tests.     

Association of low serum anticholinergic levels and cognitive impairment in elderly presurgical patients

Low-dose scopolamine, given as presurgery medication, resulted in low levels of serum anticholinergic activity and caused measurable cognitive impairment in 18 psychiatrically healthy elderly patients. The degree of impairment was directly related to serum anticholinergic activity levels and, in the small subgroup of patients scheduled for spinal anesthesia, to CSF anticholinergic activity. Two of the mental status tests used, the Rey Auditory-Verbal Learning Test and the Saskatoon Delirium Checklist, were sensitive enough to detect these mild drug-induced changes, while two other tests, the Mini-Mental State and the Symbol Digit Modalities Test, were not.     

Association of nonsteroidal anti-inflammatory drugs and aspirin with cognitive performance in middle-aged adults.

OBJECTIVES: To assess the cross-sectional association of regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin with cognitive function in 13,153 individuals, aged 48-67 years, participating in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: Regular use of NSAIDs or aspirin was analyzed in relation to the results of three cognitive tests, the Delayed Word Recall Test, the WAIS-R Digit Symbol Subtest, and the Word Fluency Test. RESULTS: After adjustment for covariates previously found to be associated with cognition in this sample, we found a weak negative association between current use of aspirin and poor Word Recall [OR = 0.84 (95% confidence interval: 0.68-1.04)] and poor Word Fluency [OR = 0.85 (0.70-1.03)]. We found no association between current use of aspirin and Digit Symbol score, nor did we find current NSAID use to be significantly associated with any of the cognitive tests. CONCLUSIONS: This study suggests a modest association, at best, between NSAIDs or aspirin and better cognitive function.     

Early HIV-related neuropsychological impairment: relationship to stage of viral infection

Sixty male outpatients with no past neuropsychiatric history were examined for evidence of early HIV-related neuropsychological impairment. Significant cognitive deficit, as measured by the RAVLT and WAIS-R Digit Symbol Substitution tests, and moderate correlation with indices of immune function, were observed in a group of patients with AIDS-Related Complex [ARC]. Patients with asymptomatic HIV-infection demonstrated no significant differences in performance compared to a group of HIV-seronegative controls. No significant group differences in age, education, predicted-IQ or self-rated depression and anxiety were observed. These results support the hypothesis that HIV-related cognitive disturbance occurs within the context of immunosuppression.     

Rapid cognitive screening in multiple sclerosis accomplished by the Free Recall and Recognition Test

This study sought to investigate the feasibility of the Free Recall and Recognition Test (FRRT) as a practical screening tool for cognitive impairment in multiple sclerosis (MS). Persons with MS (n = 227) were consecutively recruited and assessed with four cognitive tests; FRRT, Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and the Mini-Mental State Examination (MMSE). Disease severity was assessed by the Expanded Disability Status Scale (EDSS). The FRRT, which was completed by 99% of the cohort in approximately 5 minutes per assessment, correlated significantly with the other cognitive tests, as well as with the disease severity rating. A cut-off of 4 for the FRRT recall rendered 90% sensitivity and 25% specificity, and a cut-off of 4.2 for the FRRT recognition resulted in 70% sensitivity and 51% specificity. We conclude that the FRRT proved feasible as a practical screening tool for cognitive impairment in MS within a clinical setting.     

Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2

OBJECTIVE: To examine the risk factors for mild cognitive impairment (MCI) in a longitudinal population study-the Cardiovascular Health Study Cognition Study. DESIGN: We examined the factors that in the period 1991 through 1994 predicted the development of MCI in all participants of the Cardiovascular Health Study Cognition Study. Further examination was conducted in the Pittsburgh, Pa, cohort (n = 927), where participants with MCI were classified as having either the MCI amnestic-type or the MCI multiple cognitive deficits-type. SETTING: Multicenter population study. PATIENTS: This study includes all participants of the Cardiovascular Health Study Cognition Study (n = 3608) who had a magnetic resonance imaging (MRI) scan of the brain between 1991 and 1994, and detailed neuropsychological, neurological, and medical evaluations to identify the presence of MCI or dementia in the period 1998 to 1999. The mean time between the closest clinical examination to the MRI and the diagnostic evaluation for cognitive disorders was 5.8 years for the Cardiovascular Health Study Cognition Study cohort and 6.0 years for the Pittsburgh cohort. MAIN OUTCOME MEASURES: Risk factors for MCI at the time of the MRI were identified using logistic regression, controlling for age, race, educational level, baseline Modified Mini-Mental State Examination and Digit Symbol Test scores, measurements of depression, MRI findings (atrophy, ventricular volume, white matter lesions, and infarcts), the presence of the apolipoprotein E (APOE) epsilon4 allele, hypertension, diabetes mellitus, and heart disease. RESULTS: Mild cognitive impairment (n = 577) was associated with race (African American), low educational level, low Modified Mini-Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI-identified infarcts, and measurements of depression. The MCI amnestic-type was associated with MRI-identified infarcts, the presence of the APOE epsilon4 allele, and low Modified Mini-Mental State Examination scores. The MCI multiple cognitive deficits-type was associated with low Modified Mini-Mental State Examination and Digit Symbol Test scores. CONCLUSIONS: The development of MCI is associated with measurements of cognition and depression, racial and constitutional factors, and cerebrovascular disease. Early cognitive deficits seem to be a common denominator for the 2 forms of MCI; the presence of cerebrovascular disease and the APOE epsilon4 allele is associated with the amnestic type of MCI.     

Isocapnic hypoxemia and neuropsychological functioning

We evaluated the cognitive effects of hypoxemia independent of hypocapnia in 20 right-handed male subjects using a battery of brief neuropsychological tests. Results of a profile analysis indicated that performance during hypoxia was reliably different for Digit Symbol and Finger Tapping tests. Trend analysis demonstrated a significant linear pattern for Finger Tapping results, such that lower levels of oxygen were associated with slower rates of tapping. No significant trends were observed for Digit Symbol results. The observation of hypoxic effects on Digit Symbol and Finger Tapping tests is consistent with previous findings of neuropsychological changes secondary to hypoxia. The negative results observed for the remaining tests are inconsistent with past literature. It is likely that methodological differences contributed to these discrepancies, including previous reliance on inspired air to index hypoxemia rather than monitoring arterial oxygen saturation directly and failure to control for differences in CO2 levels during induced hypoxia. These variables should be controlled in future research.     

Homocysteine,white matter hyperintensities,and cognition in healthy elderly people

Hyperhomocysteinemia is associated with an increased risk of vascular disease, and recent results suggest that it also could increase the risk of dementia. We examined the relationship between homocysteine and cognitive decline in 1,241 subjects aged 61 to 73 years, followed up over 4 years. Plasma homocysteine levels were determined in all participants as well as cardiovascular risk factors, apolipoprotein E genotype, plasma levels of folate, and vitamin B12. Cognitive performances were assessed repeatedly by using Mini-Mental State Examination, Trail Making Test, Digit Symbol Substitution Test, and Finger Tapping Test. At 2-year follow-up, 841 subjects underwent cerebral magnetic resonance imaging, and white matter hyperintensities were rated visually. Analyses were adjusted for all cardiovascular risk factors. Cross-sectional analyses showed that higher concentrations of homocysteine were significantly related to poorer performances at all neuropsychological tests. Longitudinal analyses confirmed this finding. The odds of cognitive decline was 2.8-fold (p < 0.05) higher in subjects with homocysteine levels above 15 micromol/L compared with those with homocysteine levels below 10 micromol/L. In participants who underwent magnetic resonance imaging, the relationship between homocysteine and cognition was unchanged after taking into account white matter hyperintensities suggesting that white matter hyperintensities do not mediate the association between homocysteine and cognition.     

Daytime sleepiness in healthy university students: A multiparametric study

A multiparametric investigation of daytime sleepiness was performed in 18 healthy young university students. After undergoing a standard polysomnographic recording at home the night before, all subjects were evaluated by Multiple sleep latency test (MSLT) at 10.00, 12.00, 14.00, 16.00, 18.00. Subjective sleepiness (by using Visual Analogue Rating Scale) and performance tasks (Cancellation Test, Digit Symbol Substitution, Choice Reaction Time, Critical Flicker Fusion Threshold) were also assessed at the same times. Mean daily sleep latency was found to be about 10 minutes, with several individual values in the borderline range (>5 >10 minutes). Subjects did not rate themselves as excessively sleepy and there was no correlation between subjective and objective estimates of sleepiness. No consistent correlation was found between subjective-objective sleepiness and results of performance tests. Anxiety trait (Spielberg State Anxiety Trait) did not correlate with sleepiness, but higher anxiety scores were significantly associated with poor performance. These results confirm the occurrence of fairly marked objective drowsiness in healthy young subjects which, however, was not associated with subjective sleepiness and did not adversely affect performance on a variety of tests of CNS function.

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Sommario Dati della letteratura indicano che al Test di Latenza Multipla al Sonno (MSLT) soggetti giovani sani studenti di college, mostrano valori indicativi di sonnolenza diurna ai limiti superiori della norma in rapporto a restrizione cronica delle loro ore di sonno notturno dovute allo stile di vita. Nella presente indagine il livello di vigilanza diurna di soggetti giovani studenti universitari è stata testata con MSLT preceduto da poligrafia dinamica notturna domiciliare. I dati confermano l'esistenza di valori MSLT indicativi di spiccata, anche se ancora nei limiti della norma, sonnolenza diurna. Tuttavia la parallela valutazione soggettiva del livello di sonnolenza (tramite scala analogica visiva) e di test di performance (Cancellation Test, Digit Symbol Substitution, Choice Reaction Time, Critical Flicker Fusion Threshold) non ha fatto rilevare correlazioni significative con le misure MSLT. Il rendimento ai tests di performance è risultato invece essere significativamente influenzato dal tratto d'ansia (Spielberg State Anxiety Trait). I dati indicano che i livelli di sonnolenza indicati dal test neurofisiologico oggettivo, sono ben tollerati soggettivamente dai soggetti e non hanno un impatto consistente negativo su performance di tipo elementare.