Episodic memory of odors stratifies Alzheimer biomarkers in normal elderly.

OBJECTIVE: The objective of this study was to relate a novel test of identifying and recalling odor percepts to biomarkers of Alzheimer's disease (AD) in well-characterized elderly individuals, ranging from cognitively normal to demented. METHODS: One hundred eighty-three participants (cognitively normal: n = 70; subjective cognitive concerns: n = 74; mild cognitive impairment [MCI]: n = 29, AD dementia: n = 10) were administered novel olfactory tests: the Odor Percept IDentification (OPID) and the Percepts of Odor Episodic Memory (POEM) tests. Univariate cross-sectional analyses of performance across diagnoses; logistic regression modeling, including covariates of age, sex, education, APOE genotype, and neuropsychological test scores; and linear mixed modeling of longitudinal cognitive scores were performed. Amyloid deposition and MRI volumetrics were analyzed in a subset of participants. RESULTS: Accuracy of identification and episodic memory of odor percepts differed significantly across diagnosis and age, with progressively worse performance across degrees of impairment. Among the participants who were cognitively normal or had subjective cognitive concerns, poorer than expected performance on the POEM test (based on the same individual's performance on the OPID and odor discrimination tests) was associated with higher frequencies of the APOE ε4 allele, thinner entorhinal cortices, and worse longitudinal trajectory of Logical Memory scores. INTERPRETATION: Selective impairment of episodic memory of odor percepts, relative to identification and discrimination of odor percepts revealed by this novel POEM battery, is associated with biomarkers of AD in a well-characterized pre-MCI population. These affordable, noninvasive olfactory tests offer potential to identify clinically normal individuals who have greater likelihood of future cognitive decline. Ann Neurol 2016;80:846-857.

Small vessel disease and cognitive impairment: The relevance of central network connections.

Central brain network connections greatly contribute to overall network efficiency. Here we examined whether small vessel disease (SVD) related white matter alterations in central brain network connections have a greater impact on executive functioning than alterations in non-central brain network connections. Brain networks were reconstructed from diffusion-weighted MRI scans in 72 individuals (75 ± 8 years) with cognitive impairment and SVD on MRI. The centrality of white matter connections in the network was defined using graph theory. The association between the fractional anisotropy (FA) of central versus non-central connections, executive functioning, and markers of SVD was evaluated with linear regression and mediation analysis. Lower FA in central network connections was more strongly associated with impairment in executive functioning than FA in non-central network connections (r = 0.41 vs. r = 0.27; P < 0.05). Results were consistent across varying thresholds to define the central subnetwork (>50%-10% connections). Higher SVD burden was associated with lower FA in central as well as non-central network connections. However, only central network FA mediated the relationship between white matter hyperintensity volume and executive functioning [change in regression coefficient after mediation (95% CI): -0.15 (-0.35 to -0.02)]. The mediation effect was not observed for FA alterations in non-central network connections [-0.03 (-0.19 to 0.04)]. These findings suggest that the centrality of network connections, and thus their contribution to global network efficiency, appears to be relevant for understanding the relationship between SVD and cognitive impairment. Hum Brain Mapp 37:2446-2454, 2016. © 2016 Wiley Periodicals, Inc.

Everyday cognition scale items that best discriminate between and predict progression from clinically normal to mild cognitive impairment.

BACKGROUND: Impairment in instrumental activities of daily living (IADL) starts as individuals with amnestic mild cognitive impairment (MCI) transition to Alzheimer's disease (AD) dementia. However, most IADL scales have not shown IADL alterations in clinically normal (CN) elderly. The objective of this study was to determine which of the IADL-related Everyday Cognition (ECog) scale items are most sensitive for detection of early functional changes. METHODS: We assessed 290 CN and 495 MCI participants from the Alzheimer's Disease Neuroimaging Initiative. We performed logistic regression analyses predicting the probability of CN vs. MCI diagnosis using only the 17 participant-based and 17 informant-based ECog items related to IADL. We then performed Cox regression analyses to predict progression from CN to MCI. All analyses were adjusted for demographic characteristics. RESULTS: We found that worse performance on "remembering a few shopping items" (participant and informant-based p<0.0001), "remembering appointments" (participant and informant-based p<0.0001), "developing a schedule in advance of anticipated events" (participant-based p=0.007), "balancing checkbook" (participant-based p=0.02), and "keeping mail and papers organized" (informant-based p=0.002) best discriminated MCI from CN. We found that worse performance on "keeping mail and papers organized" (participant-based Hazard Ratio (HR)=2.27, p=0.07) marginally predicted greater hazard of progressing from CN to MCI. CONCLUSIONS: Our results indicate that a few simple questions targeting early functional changes, addressed either to the individual or informant, can effectively distinguish between CN elderly and individuals with MCI. Additionally, one of the above questions related to organization suggested which CN individuals are likely to progress to MCI.