Cognitive impairment and postural control deficit in adults with Type 2 diabetes.

BACKGROUND: Diseases induced by metabolic disorders, eg, Type 2 diabetes, has recently been linked to both sensory and motor deficit in the absence of a formal clinical diagnosis of peripheral neuropathy. Studies have demonstrated mild cognitive impairment in diabetic patients, which also plays a role in one's loss of ability to successfully perform basic motor activities. This project focused on evaluating cognitive function while maintaining balance. We hypothesized that simultaneous cognitive and motor deficit would occur among adults with Type 2 diabetes versus healthy age- and sex-matched control during a balance task. METHODS: A sample of 10 Type 2 diabetes patients and 10 age-matched and sex-matched controls underwent a series of sensory, motor, cognitive, and cognitive-motor evaluations. Blood pressure and A1c levels were assessed. RESULTS: Significantly lower cognitive function scores, particularly in the domain of working memory, were exhibited in the diabetic group than controls. Balance in the diabetic group was overall poorer in both single- and dual-tasks than controls. When diabetic patients were asked to verbally recall different words while maintaining their balance, their accuracy rate was significantly lower than controls. Some health state measures were found to co-vary with motor function. Increased body mass index in the diabetic group did not account for motor function deficit. SIGNIFICANCE: Our data suggest that: (1) systemic deficit beyond tactile dysfunction and increased body mass index contribute to reduced motor function in diabetes, and (2) both balance and working memory functions are simultaneously impaired in patients with Type 2 diabetes.

Frequency and Correlates of Subjective Cognitive Impairment in HIV Disease.

The increasing prevalence of older adults living with HIV has raised growing concerns about a possible rise in the incidence of neurocognitive disorders due to HIV and other age-related factors. In typical aging, subjective cognitive impairment (SCI) among individuals with normal neurocognitive functioning may be an early manifestation of an incipient neurocognitive disorder. The current study examined the frequency and correlates of SCI in 188 HIV-infected adults without performance-based neurocognitive deficits or a current psychiatric disorder and 133 HIV seronegative comparison participants. All participants completed the Prospective and Retrospective Memory Questionnaire and Profile of Mood States Confusion/Bewilderment scale. Consistent with the diagnostic criteria proposed by Jessen et al. (Alzheimers Dement 10(6):844-852, 2014), participants were classified with SCI if their scores on either of the self-reported measures was greater than 1.5 SD above the normative mean. A logistic regression controlling for current mood complaints and lifetime history of substance use disorders revealed that HIV infection increased the odds of SCI (odds ratio= 4.5 [1.6, 15.4], p = 0.004). Among HIV+ individuals, SCI was associated with lower performance-based learning and delayed memory scores (Cohen's d range 0.41-0.42.) and poorer global everyday functioning (odds ratio= 8.5 [2.6, 15.9]), but not HIV disease severity (ps > 0.10). In a sample of individuals without neurocognitive impairment or elevated mood symptoms, HIV disease was associated with a nearly fivefold increased odds of SCI compared to seronegative individuals, which may indicate an increased risk for developing major neurocognitive disorders as these HIV+ individuals age.

Cognitive and Functional Correlates of NPI-Q Scores and Symptom Clusters in Mildly Demented Alzheimer Patients.

Previous research has demonstrated an association between the emotional and behavioral symptoms of dementia, known as neuropsychiatric symptoms, and cognitive and functional decline among patients with Alzheimer disease (AD). The present study aimed to identify associations between neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and cognitive and functional performance. Participants were 256 AD patients enrolled in the Alzheimer's Disease and Memory Disorders Center at Baylor College of Medicine. An exploratory factor analysis of the NPI-Q indicated a 2-factor structure consisting of Negative/Oppositional and Anxiety/Restlessness factors. Regression analyses revealed significant associations between greater total severity of neuropsychiatric symptoms and poorer performance on basic and Instrumental Activities of Daily Living. Greater severity of Anxiety/Restlessness symptoms was associated with poor performance on measures of visuospatial functioning and basic and instrumental activities of daily living. The Negative/Oppositional factor was not related to cognition or functioning. In summary, neuropsychiatric symptoms (particularly Anxiety/Restlessness symptoms) were related to cognition and everyday functioning. Proper assessment and treatment of these symptoms is essential for improving cognition and functioning in AD patients.

Elevated rates of mild cognitive impairment in HIV disease.

With the rising number of individuals in their 50s and 60s who are infected with HIV, concerns have emerged about possible increases in the rates of non-HIV-associated dementias. The current study examined the prevalence of mild cognitive impairment (MCI) in older HIV-infected adults, since MCI is an intermediate state between typical cognitive aging and dementia that emerges in this age range. Participants included 75 adults with HIV disease aged 50 years and older who were on combination antiretroviral therapy (cART) and had undetectable plasma viral loads and 80 demographically similar HIV-seronegative comparison subjects. Participants completed a research neuropsychological evaluation that was used to classify MCI according to the comprehensive diagnostic scheme described by Bondi et al. (J Alzheimers Dis 42:275-289, 2014). HIV-infected persons were over seven times more likely to have an MCI designation (16 %) than their seronegative counterparts (2.5 %). Within the HIV+ cohort, MCI had minimal overlap with diagnoses of asymptomatic neurocognitive impairment and was significantly associated with older age, lower Karnofsky Scale of Performance Scores, and mild difficulties performing instrumental activities of daily living (iADLs). HIV infection in older adults is associated with a notably elevated concurrent risk of MCI, which may increase the likelihood of developing non-HIV-associated dementias as this population ages further.

Relationships between testosterone levels and cognition in patients with Alzheimer disease and nondemented elderly men.

BACKGROUND/AIMS: Previous research suggests that low levels of testosterone may be associated with the development of Alzheimer disease (AD), as well as poorer performance on certain neuropsychological tests and increased risk of depression. METHODS: This study utilized data from 61 nondemented older men and 68 men with probable AD. RESULTS: Testosterone levels did not differ between the groups. Regression analyses in men with AD revealed that testosterone levels did not significantly predict performance on neuropsychological tests or a measure of depression. Among controls, testosterone levels predicted estimated premorbid verbal IQ and performance on a verbal fluency test. CONCLUSION: Findings suggest that testosterone is not associated with most neuropsychological test performances in patients with AD.

Factor structure of the Geriatric Depression Scale and relationships with cognition and function in Alzheimer's disease.

BACKGROUND/AIMS: No study to date has systematically explored whether the Geriatric Depression Scale (GDS) measures symptoms of apathy and dysphoria in patients with Alzheimer's disease (AD) or related these constructs to cognitive and functional status. METHODS: Exploratory factor analysis (EFA) was used to identify factors of the GDS in a sample of 569 patients with probable AD. Two-way ANOVAs were used to determine the relationship of apathy and dysphoria to neuropsychological and functional measures. RESULTS: The EFA yielded four factors associated with apathy, dysphoria, social withdrawal and cognitive impairment. Apathy was associated with greater impairments in verbal memory, motor speed, and functional abilities. CONCLUSION: Apathy, but not dysphoria, was associated with some cognitive and functional variables. Results suggest that the GDS may be used as a screening measure for symptoms of apathy in AD.

Predictors of rate of cognitive decline in patients with amnestic mild cognitive impairment.

OBJECTIVE: Amnestic mild cognitive impairment (MCI) is a known risk factor for conversion to Alzheimer's disease (AD). Although substantial research has been conducted on the general profile of amnestic MCI subjects and predictors of conversion to AD, research on predictors of rate of decline has been considerably less extensive. The present study sought to more systematically and comprehensively examine predictors of rate of cognitive decline in a longitudinal sample of individuals with MCI, including age, genetic vulnerability, baseline cognitive performance, and baseline neuropsychiatric severity. METHOD: Participants with single or multi-domain amnestic MCI (N = 151) were assessed at baseline and for a mean of 1.32 follow-up visits (mean interval from baseline to last follow-up = 1.61 years). RESULTS: Results showed that carriers of the ApoE ε4 allele declined more quickly on all three dementia severity measures compared to non-carriers. Older individuals did not decline more rapidly in dementia severity. Participants with lower executive functions composite scores and greater memory impairment severity at baseline predicted faster decline on dementia severity measures. Contrary to hypotheses, those with lower levels of depression at baseline declined more rapidly on dementia severity measures compared to those with higher levels of depression. CONCLUSION: Identifying potential predictors of rate of decline from amnestic MCI to AD could be clinically meaningful for prognostic purposes, understanding risk and protective factors, as well as guiding future treatments and clinical trials that could aim to target and delay progression among those patients who are vulnerable to more quickly convert to AD.

An examination of the Boston Naming Test: calculation of "estimated" 60-item score from 30- and 15-item scores in a cognitively impaired population.

OBJECTIVE: Multiple versions of the Boston Naming Test (BNT) exist, which makes comparison of findings from different studies difficult. The current project sought to determine if estimated 60-item BNT scores could be reliably calculated from 30- and 15-item administrations with patients diagnosed with Alzheimer's disease (AD). METHODS: Estimated 60-item scores were created for 30-item (even and odd) and 15-item Consortium to Establish a Registry for Alzheimer's disease (CERAD) versions of the BNT from a database containing item-level responses for all BNT items. Correlations were conducted between all three estimated 60-item scores and full 60-item version scores administered to all participants in the sample. RESULTS: The estimated versions were all highly correlated with the standard 60-item version of the BNT across the sample and these findings held when the sample was separated out by case (AD) and control status. Mean difference scores were very small for scores estimated from 30-item administrations; however, difference scores for the 15-item CERAD were much larger. CONCLUSIONS: Estimated 60-item versions of the BNT can be created from 30-item BNT administrations, which will enable comparisons across studies and allow integration of data from various AD research groups for increased power in analytic protocols. Creation of an estimated score from the 15-item CERAD version is not warranted.

Decreased C-reactive protein levels in Alzheimer disease.

C-reactive protein (CRP) is an acute-phase reactant that has been found to be associated with Alzheimer disease (AD) in histopathological and longitudinal studies; however, little data exist regarding serum CRP levels in patients with established AD. The current study evaluated CRP levels in 192 patients diagnosed with probable AD (mean age = 75.8 +/- 8.2 years; 50% female) as compared to 174 nondemented controls (mean age = 70.6 +/- 8.2 years; 63% female). Mean CRP levels were found to be significantly decreased in AD (2.9 microg/mL) versus controls (4.9 microg/mL; P = .003). In adjusted models, elevated CRP significantly predicted poorer (elevated) Clinical Dementia Rating Scale sum of boxes (CDR SB) scores in patients with AD. In controls, CRP was negatively associated with Mini-Mental State Examination (MMSE) scores and positively associated with CDR SB scores. These findings, together with previously published results, are consistent with the hypothesis that midlife elevations in CRP are associated with increased risk of AD development though elevated CRP levels are not useful for prediction in the immediate prodrome years before AD becomes clinically manifest. However, for a subgroup of patients with AD, elevated CRP continues to predict increased dementia severity suggestive of a possible proinflammatory endophenotype in AD.

Benefit of phonemic cueing on confrontation naming in Alzheimer's disease.

Objective: Deficits in confrontation naming vary among persons with Alzheimer's disease (AD), including the extent to which phonemic cueing is helpful in generating the target word. This study examined neuropsychological correlates of phonemic cueing benefit and the influential effects of AD severity, estimated premorbid intellectual functioning, and apolipoprotein E genotype status.Method: Participants were 1104 individuals with mild to moderate AD who were administered the Boston Naming Test (BNT) as part of their initial neuropsychological evaluation.Results: Mild AD subjects benefited from phonemic cues significantly more than moderate AD subjects. Individuals with higher estimated premorbid IQ benefited more from phonemic cueing. Differences in phonemic cueing benefit between carriers and noncarriers of the ApoE ε4 allele were accounted for by naming ability, with carriers performing better on naming tasks compared to noncarriers. Phonemic cueing benefit uniquely contributed to cognitive performance on some semantic measures, phonemic fluency, and one nonsemantic visuospatial task.Conclusion: Individuals with probable AD who benefit more from phonemic cueing during confrontation naming tend to have higher estimated premorbid IQ and are milder in dementia severity. There is a positive association between phonemic cueing benefit and performance on select semantic measures and verbal fluency. Differences in phonemic cueing benefit between carriers and noncarriers of APOE ε4 allele can be explained by spontaneous naming performance. Results suggest complexity of underlying mechanisms involving confrontation naming, phonemic cueing, and lexical access and the factors that influence them.

How well do the ADAS-cog and its subscales measure cognitive dysfunction in Alzheimer's disease?

BACKGROUND/AIMS: The Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) is regularly used to assess cognitive dysfunction in Alzheimer's disease (AD) clinical trials. Yet, little is known about how the instrument and its subscales measure cognition across the spectrum of AD. The current investigation used item response theory (IRT) analyses to assess the measurement properties of the ADAS-cog across the range of cognitive dysfunction in AD. METHODS: We used IRT-based analyses to establish the relationship between cognitive dysfunction and the probability of obtaining observed scores on each subscale and the test as a whole. Data were obtained from 1,087 patients with AD and amnestic mild cognitive impairment. RESULTS: Results showed that the ADAS-cog and its subscales provide maximum information at moderate levels of cognitive dysfunction. Raw score differences toward the lower and higher ends of the scale corresponded to large differences in cognitive dysfunction, whereas raw score differences toward the middle of the scale corresponded to smaller differences. CONCLUSIONS: The utility of the ADAS-cog and its subscales is optimal in the moderate range of cognitive dysfunction, but raw score differences in that region correspond to relatively small differences in cognitive dysfunction. Implications for tracking and staging dementia and for clinical trials are discussed.

Cognitive and affective sequelae of primary hyperparathyroidism and early response to parathyroidectomy.

Cognitive and affective complaints are common in patients with primary hyperparathyroidism (PHPT), but few studies have used psychometric testing to document these symptoms and their response to parathyroidectomy. The current study sought to clarify the nature of cognitive and affective impairments in PHPT and changes postparathyroidectomy. One hundred eleven patients with PHPT underwent neuropsychological evaluation prior to parathyroidectomy with 68 returning for an early postsurgical evaluation. Changes in cognition were assessed using practice effect corrected reliable change indices. Biochemical and anesthesia variables were compared between groups who improved and declined. In a subset of patients, assessment revealed a significant pattern of cognitive slowing, reductions in psychomotor speed, memory impairment, and depression prior to parathyroidectomy. Postsurgical evaluations revealed a trend for improvements on timed tests and depression but a decline in memory. Older patients responded less well to surgical intervention, as did patients who experienced more dramatic changes in biochemical status following surgery. Cognitive changes early postparathyroidectomy are characterized by improved information processing speed and decline in verbal memory, with younger patients more likely to recover during this acute phase. The need for longer-term follow-up studies and increasing utilization of neuropsychological assessments in this population are discussed.

Alzheimer's disease and mild cognitive impairment deteriorate fine movement control.

Sensory-motor dysfunctions are often associated with Alzheimer's disease (AD) or mild cognitive impairment (MCI). This study suggests that deterioration in fine motor control and coordination characterizes sensory-motor deficiencies of AD and MCI. Nine patients with a clinical diagnosis of probable AD, 9 amnestic MCI subjects and 10 cognitively normal controls performed four types of handwriting movement on a digitizer. Movement time and smoothness were analyzed between the groups and across the movement patterns. Kinematic profiles were also compared among the groups. AD and MCI patients demonstrated slower, less smooth, less coordinated, and less consistent handwriting movements than their healthy counterparts. The theoretical relevance and practical implications of fine motor tasks, such as these movements involved in handwriting, are discussed relative to the deteriorated sensory-motor system of AD and MCI patients.

Semantic Memory in HIV-associated Neurocognitive Disorders: An Evaluation of the "Cortical" Versus "Subcortical" Hypothesis.

OBJECTIVE: HIV-associated neurocognitive disorders (HAND) have historically been characterized as a subcortical condition that does not affect semantic memory; however, recent evidence suggests that the cortical regions that support semantic memory may be affected in HIV. METHOD: The current study examined the effects of HAND on semantic memory in 85 HIV+ individuals with HAND, 193 HIV+ individuals without HAND, and 181 HIV- individuals who completed the Boston Naming Test (BNT) and the Famous Faces subtest of the Kauffman Adolescent and Adult Intelligence Test (KAIT-FF). RESULTS: Linear regressions revealed a significant adverse effect of HAND on total scores on the BNT and the KAIT-FF (all ps < .01). Analyses of BNT errors showed that individuals with HAND committed more semantically related errors as compared to the other two study groups (all ps < .05). However, there were no group differences in rates of visually based errors, which are more commonly observed in traditional subcortical diseases (all ps > .10). CONCLUSIONS: Results indicate that HAND may impose adverse effects on individuals' object naming and identification abilities suggestive of mild semantic deficits that parallel traditional cortical diseases such as Alzheimer's disease.

Baseline cognitive function predicts rate of decline in basic-care abilities of individuals with dementia of the Alzheimer's type.

Decline in basic self-care abilities is an important risk factor for institutionalization in individuals with dementia. The ability to predict such decline would be of clinical importance in working with families of dementia patients. Research has suggested that cognitive decline may precede loss of functional capacity. This paper utilized a large sample of probable Alzheimer's disease patients (N=150) who were evaluated longitudinally to assess the pattern of neuropsychological functioning predictive of rapid decline in self-care. The findings indicated that despite initial equality of Lawton Physical Self-Maintenance (PSM) scores, patients showing rapid decline of PSM function displayed significantly more impaired performance on neuropsychological measures at diagnosis. They also exhibited a statistically significant difference in the pattern of scores from patients who remained stable. The pattern of the rapid declining group included more severe impairment in visual spatial skills, processing speed, and concept formation. Difficulties in using individual patients' cognitive profiles to make predictions about future rate of PSM decline are discussed.

Neuropsychological function in adults with von Recklinghausen's neurofibromatosis.

The cognitive function of adults with von Recklinghausen's neurofibromatosis (NF-1) was examined. This study sought to replicate in an adult sample the findings of decreased visuospatial and attention abilities reported for many children with NF-1. Specifically, it was anticipated that adults with NF-1 would be classified separately from unaffected controls according to visual and attention-executive function skills. Second, this study examined whether language skills discriminated between adults with NF-1 and unaffected controls. The sample included 20 participants with NF-1 and 25 control participants. All participants were administered a battery of neuropsychological tests (Developmental Test of Visual-Motor Integration (VMI), Judgment of Line Orientation (JLO), Visual Form Discrimination, Booklet Category Test, Figure Cancellation, Peabody Picture Vocabulary Test-Revised (PPVT-R), Sentence Repetition, Controlled Oral Word Association). The results of a discriminant function analysis partially supported the hypothesis: Two of the tests of visual-spatial skill (VMI, JLO) and one of the language tests (PPVT-R) were found to be the best predictors for group membership. The discriminant function accounted for 45% of the variance between the groups and correctly classified 15 of the NF-1 participants and 21 of the control participants. Post hoc exploratory analyses revealed that the VMI was the most important test in discriminating between the groups. It is suggested that patients with NF-1 will tend to have sparing of basic cognitive functions but will have greater impairment on tests that use multiple cognitive skills.

Rapidly Versus Slowly Progressing Patients With Alzheimer's Disease: Differences in Baseline Cognition.

Rate of progression of cognitive deficits is variable among patients with Alzheimer's disease (AD). The purpose of the current study was to compare demographic characteristics and performance on neuropsychological measures at baseline evaluation between rapidly and slowly progressing patients. Participants were divided into 2 groups based on change in Alzheimer's Disease Assessment Scale-Cognitive subscale score from baseline to 2-year follow-up, and baseline performance was compared between the groups. Participants were 55 rapidly progressing and 55 slowly progressing patients with probable AD who had a follow-up evaluation 21 to 27 months after the baseline evaluation. The groups differed in age and initial Clinical Dementia Rating. Performance differed significantly between the groups on Verbal Series Attention Test time, Logical Memory I, Visual Reproduction I, Block Design, and Controlled Oral Word Association Test. Differences were found between rapidly and slowly progressing patients on baseline neuropsychological testing.

Prevalence and correlates of cognitive asymmetry in a large sample of Alzheimer's disease patients.

Previous research has suggested that a significant minority of patients with Alzheimer's disease (AD) exhibit asymmetric cognitive profiles (greater verbal than visuospatial impairment or vice versa) and that these patient subgroups may differ in demographic and other characteristics. Prior studies have been relatively small, and this investigation sought to examine correlates of asymmetry in a large patient sample (N = 438). Patients were classified into the following cognitive profile groups: low verbal, symmetric, and low visuospatial. Consistent with past research, 28.3% of participants were classified as having asymmetric cognitive profiles, with more participants in the low visuospatial subgroup. Low visuospatial participants were younger than members of the other subgroups, and low verbal participants performed worse on a measure estimating premorbid verbal intelligence. Findings regarding apolipoprotein E (ApoE) ε4 genotype were equivocal, although results provided some evidence for an effect of the ɛ4 allele on cognitive asymmetry. These results suggest systematic differences between neuropsychological asymmetry profiles that support the possibility of distinct subgroups of the disease.

Binomial regression with a misclassified covariate and outcome.

Misclassification occurring in either outcome variables or categorical covariates or both is a common issue in medical science. It leads to biased results and distorted disease-exposure relationships. Moreover, it is often of clinical interest to obtain the estimates of sensitivity and specificity of some diagnostic methods even when neither gold standard nor prior knowledge about the parameters exists. We present a novel Bayesian approach in binomial regression when both the outcome variable and one binary covariate are subject to misclassification. Extensive simulation results under various scenarios and a real clinical example are given to illustrate the proposed approach. This approach is motivated and applied to a dataset from the Baylor Alzheimer's Disease and Memory Disorders Center.

Individual growth curve analysis of APOE epsilon 4-associated cognitive decline in Alzheimer disease.

BACKGROUND: The apolipoprotein E epsilon4 (APOE epsilon4) allele is associated with an increased risk of developing Alzheimer disease (AD). However, findings regarding an association between the APOE epsilon4 allele and the rate of decline in AD have been mixed. OBJECTIVE: To examine the relationship between the APOE epsilon4 allele and the rate of cognitive and functional decline in AD using individual growth curve analyses. DESIGN: Longitudinal cohort study. SETTING: Alzheimer Disease Research Center at Baylor College of Medicine. PATIENTS: A total of 189 patients meeting NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) criteria for probable AD at baseline who underwent annual follow-up evaluations for at least 2 years. MAIN OUTCOME MEASURES: Individual growth curve parameters derived from baseline and follow-up performance on global and specific measures of cognitive and functional abilities. RESULTS: Patients with 2 APOE epsilon4 alleles exhibited a slower rate of decline on measures of global cognitive functioning and functional abilities. No significant association was detected between the APOE epsilon4 allele and the rate of decline on measures of specific cognitive functions. CONCLUSIONS: Although the APOE epsilon4 allele is associated with an increased risk of developing AD, it seems that having 2 APOE epsilon4 alleles is associated with a slower clinical course. These findings are consistent with hypotheses that the biological processes contributing to the onset of AD are different from those involved in determining its clinical course.