Neuropsychological changes in subjects at risk of inheriting Alzheimer's disease

Subjects from four Mexican families at risk of inheriting Alzheimer's disease (AD) were studied using a complete neuropsychological battery. These tests were repeated and compared 1 year later. Some of the experimental subjects belong to an international protocol on molecular chromosomal study. A control group matched in age and schooling was included. The subjects at risk underwent a complete physical, neurological and neuropsychological assessment. A neuropsychological battery of cognitive domains designed for the the study of dementia syndromes was administered to all subjects. Six of the subjects showed abnormal performance in cognitive functions, memory, visuospatial functions or language which persisted 1 year later. The present work describes the initial findings of a long-term prospective study aimed at delineating the neuropsychological profile of subjects at risk and to validate subtle abnormalities which in some cases could be the incipient changes of AD.     

Age-related practice effects across longitudinal neuropsychological assessments in older people with schizophrenia.

Objective: The relationship between aging and practice effects on longitudinal neuropsychological assessments was investigated in middle-aged and older people with schizophrenia and healthy controls. Method: Older people with schizophrenia (n = 107; M age = 56.1) and age-comparable nonpsychiatric controls (n = 107; M age = 57.7) were scheduled to receive annual assessments on a comprehensive battery of neuropsychological tests for an average of 2.5 years (range 11 months to 4 years). Mixed-model analyses were used to separately examine the effects of practice and age on test performance. Results: Number of prior assessments (practice) was associated with significant performance improvement across assessments, whereas older age was associated with significant decline in performance. The groups did not differ significantly in extent of age-related cognitive decline, but a three-way interaction among group, age, and practice was found, such that greater age-related decline in practice effects were found for older people with schizophrenia relative to nonpsychiatric participants. Conclusions: This study did not find any evidence of neurodegenerative age-related decline in neuropsychological abilities in middle-aged and older people with schizophrenia, but older age was associated with diminished ability to benefit from repeated exposure to cognitive tasks in people with schizophrenia. Cognitive impairment in schizophrenia may combine with cognitive decline associated with normal aging to reduce practice effects in older patients. These findings have important implications for the design of studies examining the longitudinal trajectory of cognitive functioning across the life span of people with schizophrenia, as well as clinical trials that attempt to demonstrate cognitive enhancement in these individuals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association between apolipoprotein E epsilon4 and the rate of cognitive decline in community-dwelling elderly individuals with and without dementia

OBJECTIVE: To determine whether the apolipoprotein E epsilon4 allele (apoE epsilon4) is associated with cognitive decline in individuals with and without dementia, we conducted a 4-year longitudinal study of subjects with a range of cognitive function. SETTING: At baseline, respondents (n=511) were randomly selected according to age and Mini-Mental State Examination score from a community-based study of dementia among noninstitutionalized persons aged 65 to 84 years. Respondents were examined at baseline and followed up in 3 annual visits. At baseline, subjects were classified as having normal cognitive function, minimal dementia, or dementia, according to criteria from the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) and the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Of the 511 respondents at baseline, 405 who were examined at least 2 times are included in this analysis. MAIN OUTCOME MEASURES: Cognitive decline was determined by a slope estimating yearly change in score on the neuropsychological test, the CAMCOG (the cognitive section of the CAMDEX), and its sub-scales of memory and nonmemory functions. RESULTS: Among the subjects who had normal cognitive function at baseline, apoE epsilon4 carriers showed a significantly greater decline (P<.001) in score on the CAMCOG compared with noncarriers. Differences in decline on the memory and nonmemory subtests were also significant (P<.001). Rates of cognitive decline were not related to apoE epsilon4 status in the groups with minimal dementia and dementia. CONCLUSIONS: In our community-based sample, apoE epsilon4 was associated with the rate of cognitive decline prior to the clinically symptomatic phase of dementia. Knowing the apoE epsilon4 status of those already symptomatic for dementia may not improve knowledge about a patient's prognosis.     

Cognitive screening examinations for silent cerebral infarcts in sickle cell disease

OBJECTIVE: In children with sickle cell disease (SCD), silent cerebral infarcts are the most frequent cause of neurologic injury. We determined the sensitivity and specificity of selective neurocognitive measures when separating children with silent cerebral infarcts and SCD from sibling controls. Additionally, we tested the validity of the same cognitive measures to identify patients with overt strokes. METHODS: We examined performance on a neuropsychologic battery containing measures of attention/executive, spatial, language, memory, and motor functioning for seven children with SCD and silent cerebral infarct, 21 children with SCD and overt stroke, and 17 normal siblings. Diagnosis of cerebral infarct was based on results of MRI. RESULTS: Measures from the attention and executive domains were the most useful for identifying children with silent cerebral infarct. The Test of Variables of Attention was the most robust measure and yielded a sensitivity rate of 86% and a specificity rate of 81%. This measure also showed a sensitivity rate of 95% in identifying overt stroke. CONCLUSIONS: Brief cognitive screening measures, if properly constructed, may be an effective means of identifying children with silent cerebral infarct. Future prospective studies should be pursued to assess the utility of cognitive screening for silent cerebral infarcts in SCD.     

Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Japanese patients

OBJECTIVE: To look for preclinical markers of Alzheimer's dementia in a sample of healthy, oldest old individuals. DESIGN: Prospective, longitudinal study of individuals examined at yearly intervals with neuropsychological tests selected to be sensitive to the early detection of dementia. PARTICIPANTS: One hundred and thirty-nine community-dwelling, functionally independent, healthy individuals 65 to 106 years of age who met strict criteria for lack of dementia at entry. Incident dementia cases consisted of 16 volunteers all 80 years old or older who developed dementia of the Alzheimer's type and 31 volunteers 80 years old and older showing no evidence of dementia during a mean 2.8-year follow-up interval. MEASUREMENTS: Scores on 10 neuropsychological measures were analyzed for the initial examination when none of the volunteers showed clinical evidence of dementia and for the two subsequent yearly examinations. RESULTS: Individuals who subsequently developed dementia showed evidence of verbal memory impairment at their initial examination, which was a mean of 2.8 years before clinical evidence of dementia. The average yearly incidence rate for dementia in those 80 years of age and older was 12%. Performance of individuals who did not development dementia remained relatively stable during follow-up for up to 5 years. CONCLUSION: Alzheimer's disease has a preclinical stage in which verbal memory decline is the earliest sign. Dementia in the oldest old is distinguishable from age-related cognitive decline.     

Should liver transplantation be performed for patients with chronic hepatitis B? Yes!

This study was performed to examine cognitive function in patients with end-stage heart failure, to identify possible cardiovascular factors associated with cognitive function, and to evaluate changes in cognitive function in a subgroup of patients who received heart transplantation. An extensive battery of neuropsychological tests were given to 62 patients with end-stage cardiac failure as part of their evaluation for cardiac transplantation. Most patients were consecutive referrals, not selected because of cognitive complaints. A small subgroup of transplanted (n = 7) and non-transplanted (n = 4) patients received a repeat neuropsychological examination. At initial examination, approximately 50% of the patients met criteria for impairment in reference to normal control values. Higher stroke volume index and cardiac index and lower right atrial pressure were correlated with better cognitive function. In the subgroup of patients re-examined, the transplanted patients demonstrated significantly improved cognitive function, whereas the non-transplanted subjects were unchanged. These data indicate that in patients with end-stage heart failure there is a high prevalence of impaired cognitive function which is related to measures of cardiovascular efficiency. Preliminary evidence suggests that these impairments may be partially ameliorated by cardiac transplantation.     

Preexisting dementia in stroke patients. Baseline frequency, associated factors, and outcome

BACKGROUND AND PURPOSE: The link between stroke and degenerative dementia, especially Alzheimer's disease, is closer than expected by chance. Dementia after stroke may be due to the cumulative effect of vascular and degenerative changes. The prevalence of dementia just before stroke onset remains unsettled. The aim of this study was to determine the frequency of preexisting dementia in stroke patients, associated factors, and consequences on outcome. METHODS: We evaluated the cognitive functioning prior to stroke in 202 consecutive patients with ischemic or hemorrhagic stroke by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). We classified in the dementia group patients with IQCODE scores of 104 or more. Six months after stroke onset, survivors underwent a battery of neuropsychological tests. RESULTS: Thirty-three patients were demented before stroke (16.3%; 95% confidence interval, 11.2 to 21.4). There was no diagnosis of dementia in 32 of these 33 patients. We determined by logistic regression analysis that female sex, family dementia, leukoaraiosis, and cerebral atrophy are independently associated with prestroke dementia. All survivors who had IQCODE scores of 104 or more at the acute stage met criteria for dementia 6 months later. CONCLUSIONS: Our study showed that one sixth of stroke patients have preexisting dementia. Therefore, some patients with so-called "poststroke dementia" probably had unrecognized preexisting dementia.     

Neuropsychological and psychiatric differences between Alzheimer's disease and Parkinson's disease with dementia

OBJECTIVE: To examine neuropsychological and neuropsychiatric differences between patients with probable Alzheimer's disease and patients with Parkinson's disease and dementia. METHODS: Thirty three patients with probable Alzheimer's disease and 33 patients with Parkinson's disease and dementia were matched for age, sex, and mini mental state examination scores and given a battery of neuropsychological and neuropsychiatric tests. RESULTS: Patients with Parkinson's disease with dementia had a significantly higher prevalence of major depression than patients with Alzheimer's disease; patients with Alzheimer's disease showed more severe anosognosia and disinhibition than patients with Parkinson's disease. Whereas no significant between group differences were found on tests of memory and language, demented patients with Parkinson's disease had a significantly greater impairment on a test of visual reasoning than patients with Alzheimer's disease. CONCLUSION: There were significant psychiatric differences between patients with Alzheimer's disease and demented patients with Parkinson's disease, but neuropsychological differences were restricted to a single cognitive domain.     

Lacunar infarct and deep cerebral hemorrhage: a comparison of the risk factors

INTRODUCTION: Lacunar infarcts (LI) and deep cerebral hemorrhages (DCH) have the same localization and a vasculopathy which appears to be similar, at the level of the small perforating arteries, classically attributed to arterial hypertension (AHT). OBJECTIVES: To compare the vascular risk factors of patients with lacunar ictus (LIc) and those with DCH, to try to determine how these may affect the appearance of one type of stroke or another. PATIENTS AND METHODS: We analyzed a prospective consecutive series of patients with cerebral vascular accidents (CVA), selecting 1,540 patients in the first 1,155 with a first CVA. We recorded demographic data and the following risk factors: previous transient ischemic accident (TIA), AHT, diabetes mellitus (DM), hypercholesterolemia, ischemic cardiopathy, atrial fibrillation and the presence of silent infarcts on CT. RESULTS: Two hundred and four patients had LIc and 163 had DCH. There was a significant dissociation between LIc and a history of TIA, DM, hypercholesterolemia and the presence of silent lacunar-type infarcts on CT. However, after multivariant analysis, DM did not continue to be an independent variable. Arterial blood pressure was found to be greater in the DCH group. CONCLUSIONS: The presence of different risk factors for LIc and DCH may be the key to understanding the mechanism which leads to one type or other of CVA.     

Allelic variability in D21S11, but not in APP or APOE, is associated with cognitive decline in Down syndrome

Genetic variation in the APOE gene and variation in chromosome 21 genotypes, including the APP locus, may influence age-associated cognitive decline in adults with Down syndrome. Molecular genetic and longitudinal neuropsychological analysis was performed for 41 unrelated Caucasian individuals (mean age 48.1 +/- 1.1 years (s.c.m.)) with free trisomy 21. Allele frequencies and genotype distributions were compared among subgroups with or without evidence of cognitive decline. Genetic variability at APOE and APP was not significantly associated with evidence of cognitive decline. However, aged individuals with Down syndrome, without evidence of cognitive decline, demonstrated unusual allelic variability at D21S11. These findings are discussed in the context of current hypotheses of Alzheimer-type dementia in Down syndrome and in the general population.     

The relationship between specific cognitive functions and falls in aging.

The current study examined the relationship between cognitive function and falls in older people who did not meet criteria for dementia or mild cognitive impairment (N = 172). To address limitations of previous research, the authors controlled for the confounding effects of gait measures and other risk factors by means of associations between cognitive function and falls. A neuropsychological test battery was submitted to factor analysis, yielding 3 orthogonal factors (Verbal IQ, Speed/Executive Attention, Memory). Single and recurrent falls within the last 12 months were evaluated. The authors hypothesized that Speed/Executive Attention would be associated with falls. Additionally, the authors assessed whether associations between different cognitive functions and falls varied depending on whether single or recurrent falls were examined. Multivariate logistic regressions showed that lower scores on Speed/Executive Attention were associated with increased risk of single and recurrent falls. Lower scores on Verbal IQ were related only to increased risk of recurrent falls. Memory was not associated with either single or recurrent falls. These findings are relevant to risk assessment and prevention of falls and point to possible shared neural substrates of cognitive and motor function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The validity of new memory complaints in the elderly

OBJECTIVE: To determine the validity of new subjective memory complaints (MCs) from individuals who previously, when without dementia, denied having MCs. DESIGN: Prospective cohort. SETTING: Longitudinal, community-based study of aging and dementia. PATIENTS: One hundred thirty-three community-dwelling elderly individuals who were part of a registry for the study of conditions related to aging in North Manhattan, NY. Patients were selected if they were initially without dementia and had completed at least 2 successive annual clinical and neuropsychological evaluations and provided their own medical history. MAIN OUTCOME MEASURES: Performance on memory tests--the Buschke Selective Reminding Test and a visual memory task--and global performance on a neuropsychological test battery and clinical evaluation, by which questionable dementia or dementia was diagnosed according to a well-defined paradigm. RESULTS: Fifty-three subjects with MCs at the initial evaluation performed no worse on the memory test than the 80 subjects who denied MCs initially. There was a weak association between MCs and the diagnosis of questionable dementia at baseline (P = .04), but this was nonsignificant after adjusting for age and education. At 1-year follow-up, 21 of the 80 without baseline MCs now reported MCs. At the follow-up evaluation, these 21 subjects performed significantly worse on the memory tests, were 5 times more likely to have significant cognitive impairment, and had shown significantly greater decline over the preceding year on several of the cognitive measures than the 59 who continued to deny MCs. CONCLUSION: New MCs from individuals, who when without dementia recently denied MCs, may suggest the presence of significant impairment of memory or cognition.     

Neuropsychological test performance in patients with dominantly inherited spinocerebellar ataxia: relationship to ataxia severity

To determine whether the cognitive status of patients with dominantly inherited spinocerebellar ataxia (DSCA) might be related to neurologic severity, we administered a comprehensive neuropsychological test battery to 43 patients with DSCA, ranging in ataxia severity from mild to end-stage. As compared with the controls, the mildly ataxic patients scored normally or close to normal as a group on all of the neuropsychological tests. In contrast, approximately one-half of the moderately and all of the severely ataxic patients showed poor performance, independent of age, Hamilton Rating Scale for Depression score, or education, on the Wisconsin Card Sorting Test, suggesting impaired executive system function. In addition, a subgroup of these patients had a neuropsychological profile suggestive of mild generalized cognitive impairment. We conclude that DSCA is not a homogeneous group of disorders with respect to cognitive status and that the neurologic severity of the disorder is a major factor. Impaired executive system function could be explained by damage to olivopontocerebellar system control over cerebral cortical function or to damage to other neuronal systems (especially cholinergic) that degenerate in parallel with the olivopontocerebellar system.     

Early detection of cognitive decline in higher cognitively functioning older adults: Sensitivity and specificity of a neuropsychological screening battery.

The sensitivity and specificity of a neuropsychological screening battery designed to determine early cognitive decline in the high functioning elderly are presented. The battery is composed of 4 standard neuropsychological tests assessing cognitive domains commonly effected in early stages of CNS disease. Initial validation data were gathered by applying cutoff scores derived from published or submitted normative data to test data on 2 groups of elderly, higher cognitively functioning individuals: a sample of 45 elderly individuals diagnosed with 1 of 5 target disorders, and a sample of 61 independent elderly. Cutoff scores were identified that produce high rates of correct classification and a range of sensitivity and specificity. The suggested neuropsychological test battery classifies Ss as having a high, moderate, or low probability of cognitive impairment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased expression of P-selectin on platelets is a risk factor for silent cerebral infarction in patients with atrial fibrillation: role of nitric oxide

BACKGROUND: Platelet activation and decreased levels of nitrite and nitrate (NOx), stable end products of nitric oxide (NO), are reported in patients with atrial fibrillation (AF). We examined the time-course changes in plasma NOx levels and the expression of P-selectin on platelets after the onset of AF in a canine model and determined whether these parameters could be risk factors for silent cerebral infarction in patients with AF. METHODS AND RESULTS: AF was induced by rapid atrial pacing in the canine model of AF. Plasma NOx levels were significantly decreased and the levels of P-selectin on platelets and of neutrophil/platelet conjugates were significantly increased after the onset of AF in this model. The in vitro experiments demonstrated that the inhibition of NO synthesis increased the expression of P-selectin on platelets. Plasma NOx levels (19.7+/-2.4 versus 27.5+/-2.8 micromol/L) were significantly lower in 25 patients with AF compared with age- (+/-2 years) and sex-matched control subjects. Conversely, the levels of P-selectin on platelets (7.6+/-0.8% versus 4.8+/-0.7%) and of neutrophil/platelet conjugates (14.8+/-0.9% versus 8.1+/-0.6%) were significantly higher in patients with AF. Multiple regression analysis revealed that increased P-selectin on platelets and advanced age were associated with the number of foci of silent cerebral infarction. CONCLUSIONS: An irregular heart rate that is characteristic of AF appeared to blunt NO synthesis. The increased expression of P-selectin on platelets associated with the reduced NO levels was a risk factor for silent cerebral infarction in patients with AF.     

Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study

BACKGROUND: Though among the most abundant human steroid hormones, the physiologic role of dehydroepiandrosterone and its sulfate (DHEAS) is not known. Our goal was to determine if DHEAS is associated with cognition and mood in older women, and if baseline DHEAS levels are predictive of cognitive decline. METHODS: In a prospective cohort, we studied 394 randomly selected community-dwelling women, aged 65 years or older, currently enrolled in the Study of Osteoporotic Fractures. Subjects were administered a modified Mini-Mental State Exam, Trials B, Digit Symbol, and the Geriatric Depression Scale-Shortened (GDSS), at study onset and 4-6 years later. Serum was obtained at study initiation for DHEAS analysis. RESULTS: DHEAS levels declined with age, as expected. There was no consistent association of DHEAS quartile or log DHEAS with any of the four outcomes, even after multivariate adjustment. Change in cognitive performance overtime was not associated with DHEAS levels. Analysis of the 32 women without any detectable DHEAS compared to those with detectable levels revealed higher measures on the GDSS (mean score 3.4 +/- 3.6 compared with 1.6 +/- 2.3, p = .028) and a higher percentage with depression (21.7% compared with 4.6%, p = .001). CONCLUSIONS: Serum DHEAS is not a sensitive predictor of cognitive performance or decline on a selected neuropsychological battery in elderly community women; however, nondetectable levels may be associated with depression.     

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity

Neuropsychological assessment of older individuals with dementing illnesses has suffered from a lack of appropriately designed test instruments. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was developed for the dual purposes of identifying and characterizing abnormal cognitive decline in the older adult and as a neuropsychological screening battery for younger patients. The entire battery takes less than 30 minutes to administer, and yields scaled scores for five cognitive domains. The current study reports preliminary clinical validity results with the RBANS, comparing very mildly demented patients with a diagnosis of probable Alzheimer's disease (n = 20) to patients with Huntington's disease (n = 20) and normal controls (n = 40). Although the patient groups had essentially identical total scores on the RBANS, they exhibited opposite profiles, differing significantly on four of the five subsections. The AD patients performed most poorly on Language, and Delayed Memory subsections, while the HD patients obtained their lowest scaled scores on the Attention and the Visuospatial/Constructional subsections. These results are consistent with the neuropsychological profiles of these dementing disorders derived from lengthier standardized tests and experimental investigations. In addition, even those patients who performed above the suggested cut-off points on the MMSE and the Dementia Rating Scale scored significantly below their controls on the RBANS. These data suggest that the RBANS is effective at both detecting and characterizing dementia of different etiologies.     

Unraveling the mystery of cognitive changes in old age: correlation of neuropsychological evaluation with neuropathological findings in the extreme old

In order to understand what cognitive changes can be expected with aging versus those caused by disease, the New England Centenarian Study examined correlations between neuropsychological evaluation and neuropathological studies of centenarian subjects. Sixty-nine subjects were administered an extensive neuropsychological test battery designed for centenarians. Six brain donors from this group have subsequently died, and neuropathological studies of their brains have been performed to determine the presence of Alzheimer's disease (AD) and other pathological states. Of these six centenarians, three subjects had Clinical Dementia Rating scores of 0 and no dementia on neuropsychological testing, and subsequent neuropathology showed very limited AD changes. In fact, despite a range of neuropsychological findings, none of the subjects in this series met neuropathological criteria for a diagnosis of definite AD. Findings suggest that dementia is not inevitable with aging and that dementia in this age group is surprisingly often not attributable to AD.     

Neuropsychological deficits in tests of executive function in asymptomatic and symptomatic HIV-1 seropositive men

There has been much debate about the exact nature and time of onset of the cognitive impairments associated with infection by the human immunodeficiency virus type 1 (HIV-1). Studies to date have not reached consistent conclusions. The present study comprised 22 asymptomatic and 18 symptomatic HIV-1 seropositive men, whose only risk factor for contraction of the virus was sexual intercourse, and 18 seronegative controls matched for age and IQ. Subjects were given computerized neuropsychological tests from the CANTAB battery, which assessed visuospatial memory, attention and executive function. Both the asymptomatic and the symptomatic HIV-1 seropositive subjects showed a selective pattern of deficits relative to the controls. In addition, the seropositive subjects were subtly but significantly impaired on tests of executive function but unimpaired on certain tests of visual memory. This finding supports an hypothesis that frontostriatal dysfunction occurs in HIV-1 infected individuals prior even to the expression of clinical symptoms.     

Tumor necrosis factor inhibits the transcriptional rate of glucose-6-phosphatase in vivo and in vitro

OBJECTIVE: After Alzheimer's disease, vascular dementia (VaD) and frontotemporal dementia (FTD) are among the most common dementing illnesses. FTD may have a neuropsychological profile similar to that of VaD, and patients with these dementias may be difficult to distinguish on clinical examination. The purpose of this study was to elucidate distinct cognitive profiles of a large group of FTD and VaD patients on a brief, clinical mental status examination. DESIGN: A comparison of 39 FTD patients and 39 VaD patients on a brief, clinical mental status examination. SETTING: A Dementia Research Center and affiliated, university hospitals. METHODS: The FTD patients were diagnosed by noncognitive clinical and neuroimaging criteria, and the VaD patients met NINDS-AIREN criteria for vascular dementia. The two dementia groups were comparable on three dementia assessment scales. MEASUREMENTS: The mental status measures included the neuropsychological battery from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), plus supplementation from the Neurobehavioral Cognitive Status Examination (NCSE) for cognitive areas not assessed by the CERAD). RESULTS: The FTD and VaD groups differed significantly on the mental status examination measures. FTD patients performed significantly better than the VaD patients on digit span and constructions, despite comparable performance by both groups on calculations. Although not statistically significant, the FTD group performed worse than the VaD group on verbal fluency and abstractions. These differences were not explained by group differences in age and education. CONCLUSION: These results suggest that cognitive differences between FTD and VaD groups reflect greater frontal pathology in contrast to relative sparing of posterior cortex and subcortical white matter in FTD. These cognitive differences as measured by a mental status examination may help distinguish between these two dementia syndromes.