Neuropsychologic assessment.

In this chapter, we review the use of neuropsychologic assessment in epidemiologic studies. First, we provide a brief introduction to the history of clinical neuropsychology and neuropsychologic assessment. We expand on the principal components of a neuropsychologic assessment and cognitive domains most commonly examined. This chapter also seeks to highlight specific domains and tests with validated psychometric properties that are widely accepted in clinical practice, as well as how data from a neuropsychologic test should be interpreted. Additionally, the important roles that neuropsychologic assessments play in tracking normative changes, patient diagnoses, care, and research will be discussed. Factors to consider when deciding on the inclusion of test instruments for a research study will also be reviewed. Lastly, we shed light on the contributions that neuropsychology has played in epidemiologic studies, as well as some challenges frequently faced when participating in this field of research.

Reduced binding of Pittsburgh Compound-B in areas of white matter hyperintensities.

The amyloid imaging agent, Pittsburgh Compound-B, binds with high affinity to ß-amyloid (Aß) in the brain, and it is well established that PiB also shows non-specific retention in white matter (WM). However, little is known about retention of PiB in areas of white matter hyperintensities (WMH), abnormalities commonly seen in older adults. Further, it is hypothesized that WMH are related to both cognitive dysfunction and Aß deposition. The goal of the present study was to explore PiB retention in both normal-appearing WM (NAWM) and WMH in a group of elderly, cognitively normal individuals. In a group of cognitively normal elderly (n = 64; 86.5 ± 2.6 years) two analyses were applied: (1) ROIs were placed over periventricular areas in which WMH caps are commonly seen on all subjects, regardless of WMH burden or size. (2) Subject-specific maps of NAWM and WMH were co-registered with the PiB-PET images and mean SUVR values were calculated in these NAWM and WMH maps. PiB retention was significantly reduced in the ROIs of subjects with high WMH compared to subjects with low WMH. Additionally, in subjects with high WMH, there was significantly lower PiB retention in subject-specific maps of WMH compared to NAWM, which was not observed in subjects with low WMH, likely because of the small size of WMH maps in this group. These data suggest that WM in areas of WMH binds PiB less effectively than does normal WM. Further exploration of this phenomenon may lead to insights about the molecular basis of the non-specific retention of amyloid tracers in white matter.

Association of APOE polymorphisms and stressful life events with dementia in a Pakistani population.

Dementia is a major public health problem worldwide. Alzheimer's disease (AD) is a major form of dementia and the APOE 4 allele is an established genetic risk factor for AD. Similarly, stressful life events are also associated with dementia. The objective of this study was to examine the association of APOE 4 and stressful life events with dementia in a Pakistani sample, which to our knowledge has not been reported previously. We also tested for an interaction between stressful life events and APOE 4 on dementia risk. A total of 176 subjects (61 cases and 115 controls) were recruited. All cases and healthy controls were interviewed to assess cognition, co-morbidities, history of stressful life events and demographics. Blood genotyping for the APOE polymorphism (E2/E3/E4) was performed. APOE 4 and stressful life events were each independently and significantly associated with the risk of dementia (APOE 4: P=0.00697; stressful life events: P=5.29E-09). However, we did not find a significant interaction between APOE 4 carrier status and stressful life events on risk of dementia (P=0.677). Although the sample size of this study was small, the established association of APOE 4 with dementia was confirmed the first time in a Pakistani sample. Furthermore, stressful life events were also found to be significantly associated with dementia in this population.

Functional and cognitive criteria produce different rates of mild cognitive impairment and conversion to dementia.

OBJECTIVE: To compare rates of mild cognitive impairment (MCI) and rates of progression to dementia using different MCI diagnostic systems. METHODS: MCI was investigated at baseline in 3063 community dwelling non-demented elderly in the Ginkgo Evaluation of Memory (GEM) study who were evaluated every 6 months to identify the presence of dementia. Overall MCI frequency was determined using (1) a Clinical Dementia Rating (CDR) score of 0.5 and (2) neuropsychological (NP) criteria, defined by impairment on standard cognitive tests. RESULTS: 40.2% of participants met CDR MCI criteria and 28.2% met NP MCI criteria (amnestic MCI = 16.6%). 15.7% were classified as MCI by both criteria and 47.4% as normal by both. Discordant diagnoses were observed in 24.5% who met NP normal/CDR MCI and in 12.4% who met NP MCI/CDR normal. Factors associated with CDR MCI among NP normal included lower education, lower NP scores, more instrumental activities of daily living impairment, greater symptoms of depression and subjective health problems. Individuals meeting NP MCI/CDR normal were significantly more likely to develop dementia over the median follow-up of 6.1 years than those meeting NP normal/CDR MCI. CONCLUSIONS: Different criteria produce different MCI rates and different conversion rates to dementia. Although a higher percentage of MCI was identified by CDR than NP, a higher percentage of NP MCI progressed to dementia. These findings suggest that the CDR is sensitive to subtle changes in cognition not identified by the NP algorithm but is also sensitive to demographic and clinical factors probably leading to a greater number of false positives. These results suggest that identifying all individuals with CDR scores of 0.5 as Alzheimer's disease is not advisable.

PPVT-R as an estimate of premorbid intelligence in older adults.

The Peabody Picture Vocabulary Test-Revised (PPVT-R) was examined as an estimate of premorbid intelligence in a clinical sample of elderly patients (N = 150) undergoing clinical neuropsychological evaluation. PPVT-R standard scores were compared across grossly cognitively intact, mildly/moderately and severely impaired groups of patients, and compared to a short form of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) and the Barona regression equation. Results indicate that, while the PPVT-R is vulnerable to increasing levels of cognitive impairment among patients with fewer years of education, the PPVT-R is stable across mild to moderate levels of impairment for patients with greater than 12 years of education. In a sub-sample of grossly cognitively intact patients (n = 91), the PPVT-R standard score correlated significantly with estimated WAIS-R FSIQ (r =.61). Compared to the Barona equation, the PPVT-R was less likely to over-estimate WAIS-R FSIQ in the grossly cognitively intact patients. These data suggest the PPVT-R to be a useful estimate of premorbid ability for patients with a greater than high-school education.

Clinical versus mechanical prediction: a meta-analysis.

The process of making judgments and decisions requires a method for combining data. To compare the accuracy of clinical and mechanical (formal, statistical) data-combination techniques, we performed a meta-analysis on studies of human health and behavior. On average, mechanical-prediction techniques were about 10% more accurate than clinical predictions. Depending on the specific analysis, mechanical prediction substantially outperformed clinical prediction in 33%-47% of studies examined. Although clinical predictions were often as accurate as mechanical predictions, in only a few studies (6%-16%) were they substantially more accurate. Superiority for mechanical-prediction techniques was consistent, regardless of the judgment task, type of judges, judges' amounts of experience, or the types of data being combined. Clinical predictions performed relatively less well when predictors included clinical interview data. These data indicate that mechanical predictions of human behaviors are equal or superior to clinical prediction methods for a wide range of circumstances.

Neuropsychological and oculomotor correlates of spatial working memory performance in schizophrenia patients and controls.

Recent reports of spatial working memory deficits in schizophrenia provide evidence for dorsolateral prefrontal cortical (DLPFC) dysfunction. However, the question of how spatial working memory performance relates to other task impairments in schizophrenia considered reflective of frontal dysfunction, such as the Wisconsin Card Sorting Test (WCST) and smooth pursuit eye tracking, has been largely unexplored. Spatial working memory, as measured by a computerized visual-manual delayed response task (DRT), was evaluated in 42 schizophrenia patients and 54 normal controls. Subjects also completed a battery of neuropsychological and oculomotor tasks. Schizophrenia patients performed as accurately as controls on a no-delay, sensory-motor control condition, but showed a significant impairment in spatial accuracy with the addition of an 8-s delay and verbal distraction task. For the patients, working memory impairment was associated with fewer categories on the WCST, impaired eye tracking, fewer words learned on the Rey Auditory Verbal Learning Test, but not with measures of general cognitive and clinical functioning. Results suggest the presence of a sub-group of schizophrenia patients with common pathophysiology that accounts for the co-variance of several tasks implicating prefrontal dysfunction.

Efficacy of the Continuous Visual Memory Test in lateralizing temporal lobe dysfunction in chronic complex-partial epilepsy.

The Continuous Visual Memory Test (CVMT) was hypothesized to measure nondominant temporal lobe dysfunction in patients with refractory complex-partial epilepsy. Thirty-seven temporal lobectomy candidates, of whom 20 had a right temporal seizure focus (RT) and 17 had a left temporal seizure focus (LT), were selected for study. Contrary to the hypothesis, initial results indicated that the LT group performed below the RT group for both the CVMT Total score and the Delayed Recognition score; however, group differences disappeared after accounting for Full Scale IQ scores. Both CVMT scores correlated positively and significantly with Full Scale IQ, Block Design, and the Meier Visual Discrimination Test, suggesting that overall cognitive functioning and visual-perceptual processing are positively related to CVMT performance. These results are consistent with other recent findings which suggest that extant nonverbal memory tests may be inadequate in lateralizing nondominant hemisphere lesions in complex-partial epilepsy.

The D5 dopamine receptor gene in schizophrenia: identification of a nonsense change and multiple missense changes but lack of association with disease.

To determine whether mutations in the D5 dopamine receptor gene (DRD5) are associated with schizophrenia, the gene was examined in 78 unrelated schizophrenic individuals (156 DRD5 alleles). After amplification by the polymerase chain reaction, products were examined by dideoxy fingerprinting (ddF), a screening method related to single strand conformational polymorphism analysis that detects essentially 100% of mutations. All samples with abnormal ddF patterns were sequenced. Nine different sequence changes were identified. Five of these were sequence changes that would result in protein alterations; of these, one was a nonsense change (C335X), one was a missense change in an amino acid conserved in all dopamine receptors (N351D), two were missense changes in amino acids that are identical in only some dopamine receptors and in only some species (A269V; S453C), and one was a missense change in a non-conserved amino acid (P330Q). To investigate whether the nonsense change (C335X), predicted to prematurely truncate the receptor protein and result in a 50% diminution of functional protein, was associated with schizophrenia, other neuropsychiatric diseases, or specific neuropsychological, psychophysiological, or personality traits, both case-control and family analyses were performed. No statistically-significant associations were detected with schizophrenia or other neuropsychiatric disease. There also were no significant associations between any one measure of neuropsychological function. However, a post-hoc analysis of combined measures of frontal lobe function hinted that heterozygotes for C335X may have a vulnerability to mild impairment, but these findings must be interpreted with caution.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost effectiveness of clozapine in neuroleptic-resistant schizophrenia.

OBJECTIVE: The goal of this study was to determine whether clozapine is a cost-effective treatment for treatment-resistant schizophrenia. METHOD: Data were collected on 96 treatment-resistant patients with schizophrenia for 2 years before they entered a clozapine treatment study and for at least 2 years after they entered the study. Information about the cost of inpatient and outpatient treatment, housing costs, other costs, and family burden through direct interview or questionnaire of these patients and their families were available for 47 of the 96 patients. Data on lost income and Social Security disability insurance were also obtained. Outcome measures included psychopathology, quality of life, global functioning, work function, and rehospitalization. RESULTS: The cost of treatment was significantly decreased in the patients who continued clozapine treatment for at least 2 years. This was primarily due to a dramatic decrease in the frequency and cost of rehospitalization. Costs were nonsignificantly lower in patients who dropped out of treatment. The estimated total 2-year cost for the 59 patients who continued clozapine treatment, the 34 patients who dropped out, and the three who interrupted treatment decreased from $7,390,206 to $5,719,463, a savings of $8,702/year per patient. There was a decrease in total costs of $22,936/year for the 37 patients who continued clozapine treatment for whom cost data were available. There were no significant changes in lost income or Social Security disability insurance payments in either group. Clozapine produced a marked improvement in Brief Psychiatric Rating Scale total scores as well as positive negative symptom scores, Global Assessment Scale scores, Quality of Life Scale scores, work functioning, capacity for independent living, and rehospitalization rates. CONCLUSIONS: Clozapine is a cost-effective treatment for treatment-resistant schizophrenic patients. Cost savings result almost exclusively from the reduced cost of hospitalization.