Outpatient Memory Disorders Clinic Research Articles

3 Are we Up-Front About Switching or are we Side-Stepping the Issue: Localization of Cognitive Switching Measures with Cortical Thickness

Objective:Set-shifting/switching tasks, among other measures of executive functioning, are typically thought to represent frontal lobe functioning. However, the neuroanatomical correlates of these tests are not fully established. The aim of this study was to examine associations between individual measures of set-shifting/switching and cortical thickness. We hypothesized that performance on each switching measure would strongly correlate with aggregated cortical thickness within the frontal lobe.Participants and Methods:Measures of interest included set-shifting subtests of the Delis-Kaplan Executive Function System (DKEFS): Color-Word Inhibition Switching, Category Switching, and Trail Making Test Number-Letter Switching. Archival data from an outpatient memory disorders clinic were reviewed to identify individuals whose neuropsychological evaluations included the measures of interest and had quality-assessed, volumetric MRI data available (n=243; 53.1% male, 81.9% Caucasian, Mage=72.4, SDage=6.7). Cortical thickness values were generated by FreeSurfer and averages were calculated for both frontal and temporal lobes, separately. Using partial correlations, controlling for age, we explored associations between each switching trial separately with right and left, frontal and temporal cortical thickness. The strength of associations within each lobe were then compared using Fisher's r-to-z transformations.Results:Category Switching was significantly correlated with left and right hemisphere temporal thickness (r=0.38 and 0.31, respectively), but was not significantly correlated with left or right frontal lobe cortical thickness (r=.12 and .07, respectively). Fisher's r-to-z transformations revealed significantly stronger relationships between Category Switching and temporal thickness, rather than frontal thicknesses. Trails Switching was also significantly correlated with left and right temporal cortical thickness (r=-0.28, and =-0.23, respectively) and bore weaker associations with frontal cortical thickness (r=-.13 and r = -.14 for left and right hemispheres, respectively). In contrast, Color-Word Inhibition-Switching did not show a significant relationship with frontal or temporal cortical thickness.Conclusions:Contrary to our hypothesis, stronger associations were observed with temporal lobe cortical thickness for Category Switching. Category Switching involves a language production component which could explain the strong association with temporal cortical thickness compared to frontal cortical thickness. Additionally, the pattern of associations between Trails Switching and frontal and temporal thickness was non-specific. Perhaps most striking is the lack of association between each switching measure and frontal cortical thickness, which was unexpected, given that these measures are used to assess executive functioning, broadly localized to the frontal lobe. Future directions involve examining the associations of these measure with subcortical structures and replicating these findings in larger datasets.

A-099 Depression as a Factor in Neuropsychological Test Performance

Abstract Objective Evaluate the relation between depression and performance on six widely used tests: the Boston Naming Test, Category Fluency Test, Controlled Oral Word Association Test, Corsi Block Tapping Test, Mazes and Trail Making Test (TMT), Parts Speed, A and B. Method Participants: 77 women and 33 men referred for a comprehensive neuropsychological examination in an outpatient memory disorders clinic as part of a broader neurodiagnostic workup for memory complaints and possible cognitive decline. Referral sources: neurologists (78%), primary care physicians (21%). Patients’ mean age: 59.3 (SD =12.1); education: 15.1 (SD = 2.7) years. They were screened from a larger sample (N = 175) for any known history of brain disorder or positive neurodiagnostic findings. They met performance and symptom validity criteria (Reliable Digit Span and scores on MMPI-2 validity scales). Diagnostically, 62% of the sample had mood disorders. Using their median score on the Depression scale of the MMPI-2 (T = 70), patients were classified into High and Low Depression groups (ns = 55). The two groups were no different on age, education, or predicted level of intelligence (Test of Premorbid Function). Results On all six of the neuropsychological tests (eight measures), scores were compared across the two groups. There was no main effect (MANOVA) for group, F(8,101) = 1.03, p = .427. Univariate comparisons revealed no intergroup differences across tests. Conclusion Results suggest that severity of depressive symptoms is not related to performance on these neuropsychological tests. In cooperative examinees, these tests are valid for assessing brain-based abilities independent of the examinees’ emotional status.

A-195 Emotional Factors in Performance on Halstead-Reitan/Halstead-Russell Neuropsychological Tests

Abstract Objective Evaluate the relation between depression and performance on eight widely used tests: Revised Category Test, Trail Making Test, Part B Tactual Performance Test, TPT Memory, TPT Location, Aphasia Screening Test, Seashore Rhythm Test and Speech Perception Test. Method Participants: 116 women, 71 men referred for comprehensive neuropsychological evaluation in an outpatient memory disorders clinic as part of a broader neurodiagnostic workup for memory complaints and cognitive decline. Referral sources: neurologists (78%), primary care physicians (21%). Patients’ mean age: 59.0 (SD =13.8); education: 14.9 (SD = 2.6) years. They were screened from a larger sample (N = 214) for brain disorder or positive neurodiagnostic findings. All participants satisfied performance and symptom validity criteria. Diagnostically, 62% had mood disorders. Based on Scale D scores, 65 middle-range scorers were excluded and 122 patients were classified into High and Low Depressive Symptom groups (ns = 61). The two groups were no different on age, education, Average Impairment Rating or predicted level of intelligence (Test of Premorbid Function). Results On all eight of the neuropsychological tests, scores were compared across the two groups. There was no main effect (MANOVA) for group, F(8,98) = 1.56, p = .147. Univariate comparisons revealed a trend on TPT Location but no statistically significant effects of depression severity on any of these tests. Conclusion Results suggest that severity of depressive symptoms is unrelated to performance on these neuropsychological tests. In cooperative examinees, these tests are valid for assessing brain-based abilities independent of depressive symptom severity.

Comparing the Boston Naming Test With the Neuropsychological Assessment Battery–Naming Subtest in a Neurodegenerative Disease Clinic Population

The Boston Naming Test-Second edition (BNT-2) and the Neuropsychological Assessment Battery-Naming (NAB-N) subtest are two commonly used confrontation naming tests used to evaluate word-finding ability in individuals suspected of neurodegenerative disease. The BNT-2 and NAB-N are designed to measure the same construct; however, observations in practice suggest these two tests provide divergent estimates of naming ability. This study sought to systematically investigate the level of agreement between performance on the BNT-2 and NAB-N. Records from 105 consecutive referrals seen for neuropsychological evaluation as part of routine care in an outpatient memory disorders clinic were reviewed. Discrepancy scores, concordance correlation coefficients, and root mean squared differences were calculated between demographically adjusted T-scores on the BNT-2 and NAB-N. Results indicated that estimates of word finding ability generated by the BNT-2 and NAB-N have a strong linear relationship but systematically generate scores that are inconsistent. Despite similar task demands, the BNT-2 and NAB-N provide different information about naming ability and further research is needed to understand these differences and inform clinicians on interpreting the naming estimates provided by each test.

Efficacy and Safety of Atypical Antipsychotics for Behavioral and Psychological Symptoms of Dementia Among Community Dwelling Adults

Introduction: Options for the treatment of the behavioral and psychological symptoms of dementia (BPSD) are limited. Atypical antipsychotics are often used but have questionable efficacy and are generally considered high risk. Therefore, the objective of this study is to evaluate the efficacy and safety of using any atypical antipsychotic for the treatment of BPSD among outpatients. Methods: Retrospective observational study of an academic outpatient memory disorders clinic. Participants included any community-dwelling patient with a diagnosis of dementia, not trauma induced, with documented BPSD treated with an atypical antipsychotic for at least 2 weeks. Medical records were reviewed from January 1, 1990 to March 23, 2010. Safety outcomes were documented from the time of antipsychotic initiation, and behavioral/psychological efficacy outcomes were documented beginning 2 weeks after antipsychotic therapy was initiated, until the last documentation available. Results: A total of 87 distinct antipsychotic treatment periods for 81 unique patients were included. Antipsychotic treatment was continued for more than a year in 33% of patients and only 17% of patients discontinued antipsychotic treatment over the entire period. The behavioral/psychological outcomes improved for 24 (28%) treatments, remained stable for 17 (20%) treatments, and worsened for 46 (53%) treatments. Adverse events were reported by 53% of patients, with the most common adverse events being metabolic, fall related, type, and vascular. Few adverse events were severe. The odds ratio of adverse events per every 90-day increase in duration of treatment was 1.20 (P = 0.02). Conclusion: Antipsychotic treatment improved behavioral/psychological symptoms for less than one-third of patients and increased the potential risk of adverse events for more than half of patients.

The Auditory Naming Test Improves Diagnosis of Naming Deficits in Dementia

Many patients with presumptive Alzheimer’s disease (AD) or other dementias may show minimal impairment on the Boston Naming Test (BNT), a visual confrontation naming measure. We sought to determine whether a semantic naming test, the Auditory Naming Test (ANT), would improve accuracy for identifying naming deficits in patients diagnosed with dementia ( N = 458) at an outpatient memory disorders clinic. Factor analysis revealed that both tests measured the same broad construct. Frequency of naming impairment with the ANT was significantly greater than with the BNT for patients with AD, regardless of dementia severity or levels of education ( p < .01). Effect size was moderate (φ = 0.45). BNT but not ANT performance declined with age in patients with AD. Sex differences were found for the BNT, but not the ANT, in the AD population. Accuracy rate of naming impairment diagnosis with the ANT in patients with AD was good (72%). Specificity (81%) and positive predictive value (PPV) (89%) with the ANT in AD were excellent, whereas sensitivity (69%) and negative predictive value (NPV) (58%) were modest. Receiver operating characteristic with area under the curve (ROC AUC) was excellent (0.958). A similar pattern was seen in patients with vascular dementia (VaD) or mixed AD/VaD. There was no significant effect in patients with amnestic mild cognitive impairment (aMCI). It is concluded that the ANT substantially improves the ability to diagnose naming impairment in patients with AD, VaD, and mixed AD/VaD dementia, and should be included in a neuropsychological battery administered to elderly patients with suspected dementia.

Prevalence of below-criterion Reliable Digit Span scores in a clinical sample of older adults.

The Reliable Digit Span (RDS) is a well-validated embedded indicator of performance validity. An RDS score of ≤7 is commonly referenced as indicative of invalid performance; however, few studies have examined the classification accuracy of the RDS among individuals suspected for dementia. The current study evaluated performance of the RDS in a clinical sample of 934 non-litigating individuals presenting to an outpatient memory disorders clinic for assessment of dementia. The RDS was calculated for each participant in the context of a comprehensive neuropsychological assessment completed as part of routine clinical care. Score distributions were examined to establish the base rate of below criterion performance for RDS cutoffs of ≤7, ≤6, and ≤5. One-way ANOVA was used to compare performance on a cognitive screening measure and informant reports of functional independence of those falling below and above cutoffs. A cutoff score of ≤7 resulted in a high prevalence of below-criterion performance (29.7%), though an RDS of ≤6 was associated with fewer below-criterion scores (12.8%) and prevalence of an RDS of ≤5 was infrequent (4.3%). Those scoring below cutoffs performed worse on cognitive measures compared with those falling above cutoffs. Using the RDS as a measure of performance validity among individuals presenting with a possibility of dementia increases the risk of misinterpreting genuine cognitive impairment as invalid performance when higher cutoffs are used; lower cutoffs may be useful when interpreted in conjunction with other measures of performance validity.

Validity of the Montreal Cognitive Assessment as a Screen for Mild Cognitive Impairment and Dementia in African Americans

The validity of the Montreal Cognitive Assessment (MoCA) as a screen for mild cognitive impairment (MCI) and dementia was evaluated in African Americans attending an urban outpatient memory disorders clinic. Eighty one patients ≥50 years old were administered the MoCA and neuropsychological tests. Clinicians, blinded to the MoCA scores, reviewed the neuropsychological findings and reports of instrumental activities of daily living and they assigned a diagnosis of normal cognition (NC; N = 16), MCI (N = 38), or dementia (N = 27). The MoCA scores of the 3 groups were significantly different (NC > MCI > dementia). Using cutoff scores of ≤24 points for MCI and ≤22 points for dementia, the MoCA had .95 sensitivity and .63 specificity for MCI and .96 sensitivity and .88 specificity for dementia. The MoCA is a valid and cost-effective screen for cognitive impairment in African Americans but with a higher likelihood of falsely classifying persons with NC as having MCI.

Factors related to medication adherence in memory disorder clinic patients

Medication adherence is a substantial problem in the elderly. It may be even more important among elderly persons with memory problems, since other factors that lead to non-adherence may be compounded with the memory problems themselves. The objective was to determine whether a model that integrates research on medication adherence from several research domains is useful in understanding adherence in elderly patients. The methodology involved a cross-sectional observational study using a convenience sample of 63 patients drawn from a university-affiliated outpatient memory disorders clinic. The primary measure of medication adherence was caregivers’ reports of patients’ medication adherence. Patients and their caregivers were asked questions assessing their beliefs about the seriousness of each condition for which a medication was prescribed and the likely outcome of that condition without treatment. Additional data collected included presence of side effects, total number of medications taken, and patients’ mood and cognitive status. Multilevel path analysis confirmed several model-based predictions. Caregivers’ reports of adherence were predicted by estimates of disease outcome, the presence of side effects, and patients’ relying on themselves to remember to take medications. Results partially confirm the integrative model in understanding medication adherence in these patients. Patients’ beliefs about the likely effect of medication treatment for their condition and the presence of side effects influence reported medication adherence. Results thus suggest that efforts to educate patients about the likely response of their medical condition to treatment and to assess and deal with medication side effects might improve patient adherence.

The Present State of an Outpatient Memory Disorders Clinic

The early and differential diagnosis of senile dementia is still a problem. To encourage the early referral and identification of patients with treatable conditions, an outpatient memory disorders clinic is held at our university hospital. The most frequent cause of dementia is Alzheimer's disease, followed by vascular dementia. Alzheimer's disease and vascular dementia account for 90% of causes of dementia. In 1999 donepezil hydrochloride, an acetylcholinesterase inhibitor, was approved for inhibiting disease progression in patients with Alzheimer's disease. Since then a role of an outpatient memory disorders clinic has been more important. This paper gives an outline of the clinical findings about Alzheimer's disease and vascular dementia and describes how we diagnose various types of dementia.

The Effect of a Memory Screening Program on the Early Diagnosis of Alzheimer Disease

Alzheimer Disease (AD) is often diagnosed at a moderately advanced stage, even though its early detection has become increasingly important, because of the continuing development of treatments that may improve its outcome. To determine if a free memory screening program is associated with an earlier diagnosis of AD, compared with traditional referral methods, such as by physicians and family members. A retrospective study of 1489 consecutive patients with AD who presented to an outpatient memory disorders clinic between 1993 and 2002. Subjects were classified according to referral source (memory screening, physician, family/friend, other), and self-reported ethnicity (white non-Hispanic, white Hispanic). The associations between referral source and the presenting cognitive and behavioral status of subjects were evaluated using analysis of variance and logistic regression analyses, after controlling for potentially confounding factors. Score on the Folstein Mini-Mental State Examination (MMSE), duration of cognitive symptoms, and presence of psychosis, defined as delusions and/or hallucinations. After controlling for ethnicity, gender, and the year of diagnosis, subjects with AD, who were referred by the memory screening program, scored significantly higher at presentation on the MMSE (20.8 +/- 5.7), than those referred by physicians (18.8 +/- 6.6), family/friends (16.8 +/- 6.6), or other referral sources (15.3 +/- 7.1). Subjects with AD, referred by the memory screening program, also had a lower reported duration of illness at presentation, and a decreased frequency of psychosis compared with those referred by family/friend and other methods. Other factors related to a diagnosis of AD at a later stage included female gender, Hispanic ethnicity, and a diagnosis early in the 1993 to 2002 time period. The memory screening program referred patients with AD to a memory clinic at an earlier phase of illness compared with traditional methods such as physician referral.

Apolipoprotein E polymorphism and age of onset for Alzheimer's disease in a bi-ethnic sample

This study examined the association between the Apolipoprotein-E epsilon4 allele (APOE epsilon4) and age of disease onset in a bi-ethnic sample of community dwelling Alzheimer's disease (AD) patients. Cross-sectional study of AD patients evaluated at a University-affiliated outpatient memory disorders clinic. A clinic-based cohort of white non-Hispanic (WNH; n=601) and white Hispanic (WH; n = 359) patients diagnosed with possible or probable AD according to NINCDS-ADRDA diagnostic criteria. Global cognitive functioning of the subjects was evaluated using the Mini-mental State Exam. The age of onset of AD was calculated from the patient's current age minus the reported duration of disease obtained from a knowledgeable family member. A significant relationship was discovered between APOE epsilon4 and age of onset for WNH, with lower ages of onset among patients carrying the epsilon4/epsilon4 and epsilon3/epsilon4 genotypes in relation to patients with the epsilon3/epsilon3 genotype. The results revealed a more modest effect for APOE genotype in the WH cohort, with a lower age of onset witnessed among epsilon4 positive patients (epsilon2/epsilon4, epsilon3/epsilon4 and epsilon4/epsilon4 genotypes) in comparison to epsilon4 negative patients (epsilon2/epsilon2, epsilon2/epsilon3 and epsilon3/epsilon3 genotypes). The association between the epsilon4 allele and earlier age of onset was more pronounced in WNH compared to WH patients, suggesting the impact of APOE polymorphism on clinical phenotype may be different for distinct ethnic groups in the U.S.

Relationship of behavioral and psychological symptoms to cognitive impairment and functional status in Alzheimer's disease.

This cross-sectional study examined the relationship of behavioral and psychological symptoms to cognitive and functional impairment in Alzheimer's disease (AD). One hundred and fourteen patients were evaluated consecutively at a university-affiliated outpatient memory disorders clinic and diagnosed with possible or probable Alzheimer's disease (AD) according to NINCDS-ADRDA criteria. Subjects were assessed with the Behavioral Pathology in Alzheimer's Disease Scale (BEHAVE-AD), Revised Memory and Behavior Problem Checklist (RMBPC), Blessed Dementia Scale (BDS), and Mini-Mental State Examination (MMSE). Several symptoms of behavioral pathology showed associations with MMSE scores, including activity disturbances, delusions, and hallucinations. After controlling for the variance associated with the MMSE, activity disturbances, diurnal disturbances, delusions, and hallucinations were linked with BDS scores. The results suggest that some non-cognitive symptoms may be related to the neurobiologic mechanisms underlying the increased cognitive dysfunction in AD. Specific symptoms of behavioral pathology may also impact a patient's ability to perform important self-maintenance behaviors.

PATTERNS OF DEPRESSIVE SYMPTOMS IN PATIENTS WITH ALZHEIMER's DISEASE

Purpose: Although depression is widely recognized as a significant clinical problem in patients with AD, little is known about possible types of depression in these patients. The purpose of this study was to determine whether subtypes of depressive symptoms could be empirically identified in patients with AD. Method: All patients assessed at an outpatient memory disorders clinic were administered the Cornell Scale for Depression in Dementia (Alexopoulos et al., 1988) as part of a multidisciplinary assessment.

Prevalence and correlates of Capgras syndrome in Alzheimer's disease.

This study examined the prevalence and clinical correlates of Capgras syndrome (CS) in Alzheimer's disease. Cross-sectional study of elderly patients evaluated at an outpatient memory disorders clinic classified according to the presence or absence of CS. One hundred and fifty-one consecutive patients diagnosed with probable (N=110) or possible (N=48) Alzheimer's disease (AD) utilizing NINCDS-ADRDA diagnostic criteria. The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Mini-Mental State Examination (MMSE) and Blessed Dementia Scale (BDS). CS was observed in 10% of the sample (N=16). Associated factors included other delusions, lower MMSE scores and higher BDS scores. The relation between CS and both cognitive and functional status remained significant after controlling for other delusions. CS was prevalent in approximately 10% of our community-dwelling AD sample. This syndrome was more common at the later stages of the illness and showed relations with increased functional impairment and other psychotic symptomatology.

A cross-ethnic analysis of risk factors for AD in white Hispanics and white non-Hispanics.

The prevalence of AD appears to vary widely in different ethnic groups. Certain risk factors for AD are well established for the general population, but there is little information regarding the relevance of these risk factors in specific ethnic groups. The authors examined the risk of AD associated with the APOE-epsilon4 allele, the APOE-epsilon2 allele, smoking, alcohol consumption, history of hypertension, low educational level, estrogen replacement therapy, and history of head trauma with loss of consciousness among samples of white non-Hispanics (WNH) (392 AD patients, 202 normal subjects) and white Hispanics (WHIS) (188 AD patients, 84 normal controls). This was a case-control study of patients evaluated at an outpatient memory disorders clinic and control subjects recruited from a free memory screening offered to the community. Increased risk for AD was associated with the APOE-epsilon4 allele after controlling for age, education, and gender among WNH (OR = 3.5; 95% CI = 2.3 to 5.5) and WHIS (OR = 3.1; 95% CI = 1.7 to 5.8). No protective effect was conferred by the APOE-epsilon2 allele, although this relationship approached significance among WNH (p = 0.02). Low levels of education increased the risk for AD among WNH (OR = 3.1; 95% CI = 1.8 to 5.9) but not WHIS. Alcohol use and hypertension approached significance as risk factors in WNH (p < 0.05) but not WHIS. Estrogen replacement treatment approached significance as a protective factor in both ethnic groups (p < 0.05). Although the APOE-epsilon4 allele is a risk factor for AD among WHIS and WNH, other risk factors such as low education and hypertension appear to be important only for WNH. Risk factors for AD reported or suggested previously that were not confirmed by this study include smoking and head trauma with loss of consciousness.

The behavioral pathology in Alzheimer's Disease Scale (BEHAVE-AD): factor structure among community-dwelling Alzheimer's disease patients.

The aims of this study were to (a) determine the factor structure of the Behavioral Pathology in Alzheimer's Disease Scale (BEHAVE-AD), and (b) examine the associations of the observed factors to the level of cognitive impairment. Cross-sectional study of geriatric patients evaluated at an outpatient memory disorders clinic. One hundred and fifty-one consecutive patients diagnosed with Alzheimer's disease (AD) according to NINCDS-ADRDA diagnostic criteria. Principal factors analysis with Varimax rotation resulted in a five-factor solution that accounted for 40.0% of the common variance. The factors included agitation/anxiety (agitation, anxiety of upcoming events; other anxiety), psychosis (delusions of theft, suspiciousness/paranoia; visual hallucinations), aggression (verbal aggressiveness; physical threats/violence; fear of being left alone; other delusions), depression (tearfulness; depressed mood) and activity disturbance (wandering; delusion one's house is not one's home). Several factors were associated with level of cognitive impairment as assessed by the Mini-Mental State Examination (MMSE). The results of this study suggest that the BEHAVE-AD measures a wide range of behavioral pathology that can be empirically represented by five independent symptom clusters among outpatient AD patients.