Charlie D. Morgan

Odor identification as an early marker for Alzheimer's disease: Impact of lexical functioning and detection sensitivity

The impact of lexical functioning and detection sensitivity on the deficit of odor identification in Alzheimers disease (AD) was studied in persons diagnosed with probable and questionable AD. Tests consisted of lexical-based odor identification, lexical-based picture identification, picture-based odor identification, and odor-detection threshold. Results suggest (1) that odor identification is poorer than picture identification in probable and questionable AD, (2) that odor identification continues to be poor even when lexical demands are eliminated, (3) that odor detection does contribute to the odor-identification deficit, but does not account for it completely, and (4) that odor identification tests have a correct classification rate of 83-100%. Odor identification tests can be very useful tools in diagnosing AD and should be considered an important addition to existing diagnostic test batteries.

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.

Olfactory event-related potentials: older males demonstrate the greatest deficits

Olfactory event-related potentials (OERPs) were recorded monopolarly at the Fz, Cz, and Pz electrode sites in 16 young adults (8M/8F) and 16 older adults (8M/8F) with inter-stimulus intervals (ISI) of 45, 60 and 90 s using amyl acetate as the odorant stimulus. N1, P2, and N2 peak amplitudes and latencies were measured. Young participants demonstrated significantly shorter peak latencies than older participants. Older males demonstrated significantly smaller peak amplitudes than the other participant groups. Peak amplitudes also increased with longer ISIs for older males. The OERP is compared to traditional olfactory psychophysical testing.

Olfactory event-related potentials in Alzheimer's disease.

Areas of the brain affected in the early stages of Alzheimers disease are also areas heavily involved in the processing of olfactory information. Olfactory event-related potentials (OERPs) and auditory ERPs were recorded from the Fz, Cz, and Pz electrode sites in 12 Alzheimers disease (AD) patients and 12 age and gender matched normal controls (NC) in a single-stimulus paradigm with a 45 s inter-trial interval, using amyl acetate as the olfactory stimulus, and in a separate session a 500 Hz tone as the auditory stimulus. Odor identification (ID) was also used to assess ability to identify odors. The results indicate that (1) OERP P2 and P3 latencies were significantly longer in AD patients than normal controls; (2) olfactory ERP latency measures correlated significantly with dementia status as measured by the Dementia Rating Scale (DRS), indicating that as participants performed more poorly on the DRS, reflecting increased dementia, OERP latencies increased; (3) olfactory ERP latency measures better differentiated AD patients from normal controls than auditory ERP latency measures; (4) olfactory ERP measures alone correctly classified up to 92% of participants; (5) odor ID measures, namely the UPSIT and San Diego-Odor-ID tests also classified participants at a high rate. Combining scores for odor identification with olfactory P3 latency measures resulted in a correct classification rate of 100%. The results strongly support the use of olfactory measures in the assessment of AD.

Olfactory P3 in young and older adults.

Olfactory event-related potentials (OERPs) were recorded monopolarly at the Fz, Cz, and Pz electrode sites in 16 young adults and 16 older adults to assess aging effects on the olfactory P3. Amyl acetate was used to elicit the OERPs, with an intertrial interval of 45 s. Young adults produced significantly larger P3 amplitudes and shorter P3 peak latencies than older adults. The olfactory P3 response appears to be sensitive to age-related changes in the olfactory system and may reflect cognitive slowing in the central nervous system.

Olfaction in Aging and Alzheimer's Disease

Alzheimers disease (AD) is a devastating neurodegenerative condition that affects more than 5 million Americans. Currently, a definitive and unequivocal diagnosis of AD can only be confirmed histopathogically via postmortem autopsy, demonstrating the need for objective measures of cognitive functioning for those at risk for AD. The single most important genetic risk factor of AD is the apolipoprotein E (ApoE) ɛ4 allele. The present study investigated olfactory and cognitive processing deficits in ApoE ɛ4+ individuals using a cross‐modal recognition memory task and an objective electrophysiological measure, the event‐related potential (ERP). Ten ɛ4+ individuals (5 M, 5 F, mean [M]= 75.1 years) and 10 age‐ and gender‐matched ɛ4− individuals (5 M, 5 F, M = 71 years) sequentially encoded a set of 16 olfactory stimuli and were subsequently shown names of odors previously presented (targets) or not (foils). EEG activity was recorded from 19 electrodes as participants distinguished targets from foils using a two‐button mouse. P3 latencies were significantly longer in ɛ4+ individuals, and intraclass correlations demonstrated differential activity between the two groups. These findings are consistent with a compensatory hypothesis, which posits that nondemented ɛ4+ individuals will expend greater effort in cognitive processing or engage in alternative strategies and therefore require greater activation of neural tissue or recruitment of different neural populations. The findings also suggest that cross‐modal ERP studies of recognition memory discriminate early neurocognitive changes in ApoE ɛ4+ and ApoE ɛ4− individuals and may contribute to identifying the phenotype of persons who will develop Alzheimers disease.

Differential Effects of Active Attention and Age on Event-related Potentials to Visual and Olfactory Stimuli

Normal aging impairs olfactory functioning both centrally and peripherally. The P3 peak of the event-related potential (ERP), evoked by active response to a target stimulus, is considered a reflection of central cognitive processing. It can also be evoked in a passive task to both auditory and visual stimuli. Our goal was to investigate whether age influences amplitude and latency of the ERP differentially in active and passive tasks to olfactory stimuli. Olfactory and visual event-related potentials were elicited with a single stimulus paradigm in separate active and passive task response conditions. Participants included 30 healthy individuals from three age groups, young, middle age, and older adults. Results indicated that P3 ERP latency increased with age in both sensory modalities. P3 latencies for active versus passive tasks were similar across age groups for visual ERPs, but in the olfactory modality, older adults demonstrated significantly longer latencies in the passive task compared to the active task. Future directions should include research on specific clinical populations utilizing active versus passive task conditions.

Individuals at risk for Alzheimer's disease show differential patterns of ERP brain activation during odor identification

BackgroundStudies suggest that older adults at risk of developing Alzheimer’s disease may show olfactory processing deficits before other signs of dementia appear.MethodsWe studied 60 healthy non-demented individuals, half of whom were positive for the genetic risk factor the Apolipoprotein E ɛ4 allele, in three different age groups. Event-related potentials to visual and olfactory identification tasks were recorded and analyzed for latency and amplitude differences, and plotted via topographical maps.ResultsVarying patterns of brain activation were observed over the post-stimulus epoch for ɛ4- versus ɛ4+ individuals on topographical maps. Individuals with the ɛ4 allele demonstrated different ERP peak latencies during identification of olfactory but not visual stimuli. High correct ApoE classification rates were obtained utilizing the olfactory ERP.ConclusionsOlfactory ERPs demonstrate functional decline in individuals at risk for Alzheimer’s disease at much earlier ages than previously observed, suggesting the potential for pre-clinical detection of AD at very early stages.

Age and apolipoprotein E ε4 effects on neural correlates of odor memory.

Alzheimers disease (AD) affects 5.4 million Americans. Evidence suggests that individuals who are positive for the apolipoprotein E (ApoE) ε4 allele are at higher risk for developing the disease. Studies have also shown that the ε4 allele is linked to olfactory decline. Olfactory functioning may be investigated using olfactory event-related potentials (OERPs). The high temporal resolution of OERPs enables an understanding of the neural correlates of olfactory processing and functioning. This study investigated the effects of age, ApoE ε4 status, response type, and electrode site on OERP latency and amplitude during encoding and retrieval in an odor recognition memory task. The 60 participants were equally divided into 3 age groups matched on ε4 status: younger, middle, and older. Odors were presented using a computer-controlled olfactometer. Participants were notified during encoding that this was a task of odor memory. Results indicated differences in OERP activity as a function of age, ApoE ε4 status, response type, and electrode site. These findings highlight the potential of OERPs to distinguish ε4- and ε4+ individuals and to contribute to an earlier diagnosis of AD.

Abnormal event-related potentials in young and middle-aged adults with the ApoE ε4 allele.

The largest genetic susceptibility factor for Alzheimers disease is the Apolipoprotein E (ApoE) ε4 allele. Cognitive decline and olfactory impairment are greater in those positive for the ε4 allele. This study sought to determine if the olfactory event-related potential (OERP), compared to the visual ERP, would be sensitive to these subtle declines. Participants included 40 individuals from two age groups, half of each group were ε4 allele positive and half were ε4 negative. Visual ERPs did not demonstrate significant differences between ApoE groups. OERPs demonstrated robust age by ApoE interactions. P3 latencies were significantly longer in ε4 young and middle age participants. These findings suggest that very early olfactory and cognitive changes related to ApoE status are detectible via the OERP.