Alexandra Varjassyova

Human Analogue of the Morris Water Maze for Testing Subjects at Risk of Alzheimer’s Disease

Background: Patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (MCI) have difficulties with spatial orientation. Objective: To test hypothesis that spatial navigation is impaired early in MCI patients representing the presymptomatic stage of AD. Methods: We tested patients with probable AD (n = 21), MCI, further classified according to Petersen’s criteria as amnestic MCI (aMCI) single domain (n = 11), aMCI multiple domain (n = 31), or nonamnestic MCI (n = 7). The aMCI group was also stratified using cued recall according to Dubois’ criteria into memory impairment of the hippocampal type (n = 10) and isolated memory retrieval impairment-nonhippocampal (n = 32) and also according to ApoE4 status into E4+ (n = 12) and E4– (n = 30). These patients and controls (n = 28) were tested in the human variant of the Morris water maze. Depending on the subtest, the subjects could use the egocentric or allocentric (hippocampus-dependent) navigation. Results: The AD and aMCI multiple domain groups were impaired in all subtests. The aMCI single domain group was impaired in allocentric subtests. The hippocampal MCI group performed poorer than the nonhippocampal MCI group and similarly to the AD group. The ApoE4+ group was as bad as the AD group when compared with the E4– group. Conclusion: aMCI subjects represent a very heterogeneous population, and spatial memory or cued recall examination can add more value to aMCI classification. ApoE4+ patients are more impaired than ApoE4– patients.

From Morris Water Maze to computer tests in the prediction of Alzheimer's disease.

Background: Spatial navigation performance in the Hidden Goal Task (HGT), a real-space human analogue of the Morris Water Maze, can identify amnestic mild cognitive impairment (aMCI) patients with memory impairment of the hippocampal type, a known indicator of incipient Alzheimer’s disease (AD). Objective: Contrast results from computer versus real-space versions of the HGT. Methods: A total of 42 aMCI patients were clinically and neuropsychologically classified into: (1) memory impairment of the hippocampal type – the hippocampal aMCI (HaMCI; n = 10) and (2) isolated retrieval impairment – the nonhippocampal aMCI (NHaMCI; n = 32). Results were compared to the control (n = 28) and AD (n = 21) groups. Results: The HaMCI group, although similar to the NHaMCI group with respect to overall cognitive impairment, performed poorer on the computer version of the HGT and yielded parallel results to the real-space version. The two versions were strongly correlated. Conclusions: Both versions of the HGT can reliably identify aMCI with pronounced memory impairment of the hippocampal type. The computer version of the HGT may be a useful, relatively inexpensive screening tool for early detection of individuals at a high risk of AD.

Recognition of Facial Emotional Expression in Amnestic Mild Cognitive Impairment

We examined whether recognition of facial emotional expression would be affected in amnestic mild cognitive impairment (aMCI). A total of 50 elderly persons met the initial inclusion criteria; 10 were subsequently excluded (Geriatric Depression Score > 5). 22 subjects were classified with aMCI based on published criteria (single domain aMCI [SD-aMCI], n = 10; multiple domain aMCI [MD-aMCI], n = 12); 18 subjects were cognitively normal. All underwent standard neurological and neuropsychological evaluations as well as tests of facial emotion recognition (FER) and famous faces identification (FFI). Among normal controls, FFI was negatively correlated with Mini-Mental Status Examination scores and positively correlated with executive function. Among patients with aMCI, FER was correlated with attention/speed of processing. No other correlations were significant. In a multinomial logistic regression model adjusted for age, gender, and education, a poorer score on FER, but not on FFI, was associated with greater odds of being classified as MD-aMCI (odds ratio [OR], 3.82; 95% confidence interval [CI], 1.05-13.91; p = 0.042). This association was not explained by memory or global cognitive score. There was no association between FER or FFI and SD-aMCI (OR, 1.13; 95% CI, 0.36-3.57; p = 0.836). Therefore, FER, but not FFI, may be impaired in MD-aMCI. This implies that in MD-aMCI, the tasks of FER and FFI may involve segregated neurocognitive networks.

APOE E4 affects spatial working memory and attention in patients with amnestic mild cognitive impairment

6 3.8, namci-s: 179.6 6 11.2, namci-m: 143.6 6 19.9). There were significant differences on the scores of SNSB-D and several cognitive domains of language, visuospatial function, memory and frontal executive function among the subtypes of MCI. According to post-hoc analysis, the subtypes of amnestic and non-amnestic multi-domian MCI showed more deficits in all cognitive domains compared with other types of MCI. Conclusions: Our study shows characteristic and different pattern of cognitive deficits in patients with MCI, and these results may be helpful to predict the conversion tendency to dementia conditions according to subtypes of MCI.

Spatial navigation computer test can discriminate two types of amnestic mild cognitive impairment

Participants (n 1⁄4 300) included cognitively normal community volunteers and patients with mild cognitive complaints, all of whom were not demented at baseline, had been clinically evaluated, and were followed annually as part of a longitudinal study of Mild Cognitive Impairment (MCI) at the Joseph and Kathleen Bryan ADRC at Duke (18% African American; mean age 1⁄4 75 [8.8sd]). Diagnoses for prAD, functional MCI (CDR 1⁄4 0.5) and revised prAD were algorithmically applied retrospectively, as was done in previous work. Diagnostic stability, assessed by positive and negative predictive values (PPV, NPV) and reversion rates over three years of follow-up, was examined in the AfAm and Caucasian subgroups. Results: At baseline, approximately half of the participants met criteria for prAD and fMCI, while only 9% met criteria for revised prAD. The reversion rate to cognitively normal status in each impaired group was low (1016%), though substantially higher in AfAms (30%). Prediction of later dementia at one year was highest for the revised prAD criteria (ppv 1⁄4 0.32) compared to fMCI (ppv 1⁄4 .09) and the original formulation of prAD (ppv 1⁄4 0.08). NPVs were consistently high across all diagnostic entities (.961.0). Conclusions: Current results suggest that diagnosing early AD in its prodromal stage across diverse groups is facilitated by clinical criteria which require objective evidence of both memory disorder and either executive dysfunction or functional decline. However, there is a higher degree of diagnostic instability in AfAm using this approach, possibly due to cultural differences in psychometric test performance or due to other variables that may be changing with time (e.g. disease co-morbidities). The findings require further investigation in a larger sample before applied as a screening method.

P1-213: Relation atrophy of the amygdala to emotional impairment in Alzheimer's disease

en’s criteria. Telephone testing with MCAS was conducted an average of 15 days after an office visit. Diagnoses were established by consensus conference. Results: For MCAS total scores, the AD group performed significantly worse than the MCI group, who in turn performed worse than the HC group. MCAS total scores significantly correlated with in-office Mini Mental State Examination (r 0.77). Linear discriminant analysis, based upon MCAS subtest scores, revealed that none of AD subjects was misclassified as HC or MCI (95% CI 0%-20%). Among MCI subjects, 17% (95% CI 0%-23%) were misclassified as HC, whereas 3% (95% CI 0%-10%) were misclassified as AD. Among HC subjects, 17% (95% CI 0%-28%) were misclassified as MCI, whereas none was misclassified as AD (95% CI 0%-6%). Conclusions: Our results suggest that this brief telephone cognitive screen performs well at distinguishing AD from MCI and healthy older adults. Although the test was less accurate in discriminating MCI from HC, findings are promising given the diagnostic complexity of these cases. Thus, the MCAS has potential as a screening tool for both clinical and research settings in identifying patients with a range of memory disorders.