Spencer Wetter

Olfactory event-related potentials and aging: normative data.

Unlike the clinical usages of evoked potentials (e.g. brain stem auditory evoked potentials for the assessment of auditory function), normative data for the olfactory event-related potential (OERP) have been unavailable. The principal objective was to establish normative data across the human life span for OERPs with a given set of parameters. Participants were 140 persons from seven age groups (16-19, 20-29, 30-39, 40-49, 50-59, 60-69 and 70-79 years of age), with equal numbers of males and females, screened for nasal health and dementia. The odor stimulus was amyl acetate, presented at nasal temperature in a humidified airstream delivered by an air-dilution olfactometer at a constant flow rate, using a 60-s inter-stimulus interval. OERPs were recorded at Fz, Cz, and Pz electrode sites, amplified and averaged over trials. Amplitudes of the N1/P2 and P3 and latencies of the P2 and P3 were analyzed. Processing speed decreased at a constant rate over decades for the sensory (P2 latency) as well as cognitive (P3 latency) components. Decline in amplitude over decades was also apparent. Normative data will be useful in research on olfactory function and in clinical assessment of olfactory functional status.

Response inhibition and set shifting in patients with frontal lobe epilepsy or temporal lobe epilepsy

Patients with frontal lobe epilepsy (FLE), patients with temporal lobe epilepsy (TLE), and matched controls were administered a test of response inhibition and set shifting (switching) (Color Word Interference Test, CWIT). Patients with FLE were impaired relative to the controls across all conditions of the CWIT, with the FLE patients showing disproportionate impairment in the Inhibition and Inhibition/Switching conditions. In contrast, the TLE patients did not differ from controls. Further analysis of the patient groups revealed that patients with left FLE were impaired relative to those with right FLE, left TLE, and right TLE in the Inhibition condition. In the Inhibition/Switching condition, patients with left FLE and left TLE were impaired relative to their right-sided counterparts. Finally, performance by the TLE group in the Inhibition/Switching condition was correlated with seizure frequency. These data suggest that patients with FLE, but not TLE, show impaired inhibition and set shifting relative to controls. In addition, side of the seizure focus and seizure frequency may contribute to executive dysfunction in patients with epilepsy.

Creativity Lost: The Importance of Testing Higher-Level Executive Functions in School-Age Children and Adolescents

In school settings, students are typically evaluated using group achievement tests, IQ scales, and college entrance exams that focus more on rote-verbal skills (e.g., vocabulary, mathematical facts) than on higher level executive functions (e.g., abstract thinking, problem solving). However, recent neuropsychological findings suggest that rote-knowledge skills and executive functions are divergent cognitive domains that can be dissociated in both adults with frontal lesions and children with neurodevelopmental disorders. New correlational findings obtained from 470 children and adolescents provide additional support for the divergent nature of these cognitive domains and the existence of subgroups of students who exhibit either strengths in abstract, creative thinking with relative weaknesses in rote-verbal skills or vice versa. The results suggest that current school assessment practices may result in academic roadblocks for those students who have strengths in abstract, creative thinking but whose relative weaknesses in rote-verbal skills may hinder their ability to take college entrance exams.

Deficits in inhibition and flexibility are associated with the APOE-E4 allele in nondemented older adults.

This prospective study of nondemented older adults at genetic risk for AD and other types of dementia (i.e., APOE e4 allele) utilized a new Stroop test that includes a dual executive-function condition requiring both response inhibition and cognitive switching. Results indicated that, relative to non-e4 subjects, the e4 group committed more errors, but only on the new Inhibition/Switching condition. In addition, error-rate variance on this task was more heterogeneous for the e4 compared to the non-e4 group, and errors rates correlated significantly with global cognitive status (i.e., DRS scores) for the e4 group but not for the non-e4 group. These findings suggest that vulnerability to errors in response inhibition and cognitive flexibility is present in persons at risk for AD and may signal early emergence of executive dysfunction in preclinical AD. The association between these subtle executive-function deficits and the overall cognitive functioning of at-risk individuals provides further evidence of their utility as a possible preclinical marker of AD. Preparation of this article was supported in part by a Veterans Administration Merit Review Grant (DD), a VA Career Development Award (MJ) and by National Institute on Aging Grants RO1 AG12674 (MB) and P50 AG05131 (UCSD ADRC; DS).

Individuals with Down's syndrome demonstrate abnormal olfactory event-related potentials

OBJECTIVE Recent research has demonstrated that individuals with Downs syndrome (DS) develop plaques and tangles in the brain similar to people with Alzheimers disease. As a result, they show increased dementia and decreased olfactory functioning compared to healthy individuals. The olfactory event-related potential (OERP) has been used as an objective quantitative measure of olfactory functioning in normal and clinical populations. The present study investigated the utility of the latency and amplitude of the OERP components in examining olfactory dysfunction in DS individuals. METHODS OERPs were recorded monopolarly at the Fz, Cz and Pz electrode sites, using amyl acetate at a 60 s inter-stimulus interval, from individuals with DS (mean age 26.0 years) and age-matched normal controls. Participants were screened for nasal health and odor thresholds were assessed. Dementia was assessed using the dementia rating scale (DRS). RESULTS Results indicate that DS subjects have significantly longer latencies in the sensory (N1, P2, and N2) and cognitive (P3) components of the OERP than normal controls. Odor threshold was significantly associated with sensory OERP components. In addition, DS subjects with a higher level of dementia showed significantly longer P3 latencies than those with lower dementia levels. CONCLUSIONS The study suggests that the OERP may be a useful measure of olfactory dysfunction in DS which may precede developing dementia in this population.

Impairments in source memory for olfactory and visual stimuli in preclinical and clinical stages of Huntington's disease

Individuals in preclinical and clinical stages of Huntingtons disease (HD) demonstrate impairments in olfactory functioning. In addition, HD patients are impaired in source memory for verbal stimuli. A task combining both source and odor memory may be particularly sensitive to early changes in HD. The present study examined source and item memory for olfactory and visual stimuli in 10 individuals with HD, 10 asymptomatic HD gene carriers, 8 nongene carriers who had a parent with HD, and 20 normal controls. During the study phase, a male and a female experimenter (sources) presented odors and objects to the participant in an alternating sequence. To assess item memory, a stimulus from the study phase (target) and a novel stimulus (distractor) were presented, and the participant was asked to choose the target. To assess source memory, the experimenter presented a stimulus and asked whether the male or female experimenter had previously presented the stimulus. Results indicate that source memory for both visual and olfactory stimuli was impaired in HD patients compared to normal controls. In asymptomatic gene carriers, however, source memory for olfactory stimuli, but not visual stimuli, was more impaired than in nongene carriers and normal controls. Furthermore, gene carriers and HD patients showed a similar degree of impairment in source memory for olfactory stimuli. The only significant impairment found in item memory was for olfactory stimuli in HD patients. These results suggest that source memory for olfactory stimuli may be particularly sensitive to neuropathological changes in preclinical stages of HD.

Apolipoprotein E ε4 positive individuals demonstrate delayed olfactory event-related potentials

Apolipoprotein E e4 positive individuals have deficits in the ability to identify and remember odors, as demonstrated by psychophysical measures of olfactory function. The purpose of the present study was to identify olfactory deficits in this population using an objective electrophysiological measure: the olfactory event-related potential (OERP). Olfactory and auditory ERPs were recorded from the Fz, Cz, and Pz electrode sites in 10 e4 positive individuals and 10 age and gender-matched e4 negative individuals in a single-stimulus paradigm. The results indicate: (1) individuals who are positive for the apolipoprotein E e4 allele demonstrated delays (of approximately 100 ms) in the processing of olfactory information compared to those who are e4 negative; (2) OERP latency is more sensitive than psychophysical measures of olfactory function; (3) delays in the cognitive P3 component of the OERP are associated with deficits in the ability to identify an odor; and (4) unlike the moderate ranges found in auditory ERP, OERP latency showed high sensitivity and specificity in classifying e4 positive and negative individuals.

Identifying the “source” of recognition memory deficits in patients with Huntington's disease or Alzheimer's disease: Evidence from the CVLT-II

The present study compared the performance of individuals with Huntingtons disease (HD) and Alzheimers disease (AD) on three types of California Verbal Learning Test–Second Edition (CVLT-II) recognition discriminability indices (RDI): Source, Novel, and Total. The HD and AD groups did not differ significantly on Source RDI (all 16 targets versus the 16 previously presented, List B, distractors). However, HD patients performed significantly better than AD patients on Total RDI (all 16 targets versus all 32 distractors) and Novel RDI (all 16 targets versus 16 new distractors). Implications of these findings on the differentiation of the memory disorders associated with HD and AD are discussed.

Cognitive Discrepancies Versus APOE Genotype as Predictors of Cognitive Decline in Normal-Functioning Elderly Individuals: A Longitudinal Study

OBJECTIVES Cognitive-discrepancy analysis has been shown to be a useful technique for detecting subtle cognitive deficits in normal-functioning elderly individuals who are genetically at-risk for Alzheimer disease (AD). However, studies that have used cognitive-discrepancy measures to date have used retrospective or cross-sectional designs, and the utility of this approach to predict cognitive decline has not been examined in a prospective investigation. DESIGN Longitudinal study. SETTING San Diego, CA, Veterans Administration Hospital. PARTICIPANTS Twenty-four normal-functioning elderly individuals participated in the study, with 16 subjects exhibiting no change in their Dementia Rating Scale (DRS) scores over an 1-year period (Stable Group), and 8 subjects exhibiting a decline in DRS scores over the 1-year period (Decline group). MEASUREMENTS A cognitive-discrepancy measure isolating cognitive switching was computed that contrasted performance on a new higher-level task of executive functioning (a Stroop/Switching measure) relative to a composite measure of lower-level Stroop conditions. RESULTS a) In the year before their cognitive changes, the Decline group exhibited a significantly larger cognitive-discrepancy (Stroop/Switching versus lower-level Stroop conditions) score compared with a control (Stable) group; and b) the cognitive-discrepancy measure was superior to APOE genotype in predicting DRS decline. CONCLUSION Cognitive-discrepancy analysis isolating a component executive function ability not only seems to be a useful tool for identifying individuals at risk for cognitive deficits, but also shows promise in predicting individuals who may show subtle cognitive decline over time.

Asymmetries in Global-Local Processing Ability in Elderly People With the Apolipoprotein E-ε4 Allele.

Previous studies have identified cognitive asymmetries in elderly people at increased risk for Alzheimers disease (AD) by comparing standardized neuropsychological tests of verbal and spatial abilities in both preclinical AD and apolipoprotein epsilon4+ elderly groups. This prospective study investigated cognitive asymmetries within a single test by comparing cognitively intact elderly (with and without the epsilon4+ allele) on a learning and memory measure that uses global and local visuospatial stimuli. Both groups demonstrated comparable overall learning and recall. But the epsilon4+ group had a significantly larger discrepancy between their global and local learning scores and had a greater proportion of individuals with more than a one standard deviation difference between their immediate recall of the global and local elements, relative to the epsilon4- group. These findings build on previous studies identifying subgroups of elderly people at greater risk for AD who often demonstrate increased cognitive asymmetries relative to groups without significant risk factors.