Follow-Up Study of Olfactory Deficits, Cognitive Functions, and Volume Loss of Medial Temporal Lobe Structures in Patients with Mild Cognitive Impairment

Łojkowska, Wanda; Sawicka, Beata; Gugala, M.; Sienkiewicz-Jarosz, Halina; Bochyńska, Anna; Ścińska, Anna; Korkosz, Agnieszka; Łojek, Emilia; Ryglewicz, Danuta

doi:10.2174/156720511796717212

Cited by 33 publications

(33 citation statements)

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“…Lastly, altered response to an attractant scent in AD mice is consistent with reported deficits in odor-based memory formation [60]. This deficit may be conceptually related to the early olfactory deficits in MCI patients [61], who are at particular risk to develop AD [62, 63]. Taken together, the current behavioral model is consistent with previous observations and interpretations.…”

Section: Discussionsupporting

confidence: 88%

Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

Marchese

Cowan

Head

et al. 2014

JAD

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Background Immune system activation is frequently reported in patients with Alzheimer's disease (AD). However, it remains unknown whether this is a cause, a consequence, or an epiphenomenon of brain degeneration. Objective The present study examines whether immunological abnormalities occur in a well-established murine AD model and if so, how they relate temporally to behavioral deficits and neuropathology. Methods A broad battery of tests was employed to assess behavioral performance and autoimmune/inflammatory markers in 3xTg-AD (AD) mice and wild type controls from 1.5 to 12 months of age. Results Aged AD mice displayed severe manifestations of systemic autoimmune/inflammatory disease, as evidenced by splenomegaly, hepatomegaly, elevated serum levels of anti-nuclear/anti-dsDNA antibodies, low hematocrit, and increased number of double-negative T splenocytes. However, anxiety-related behavior and altered spleen function were evident as early as 2 months of age, thus preceding typical AD-like brain pathology. Moreover, AD mice showed altered olfaction and impaired “cognitive” flexibility in the first 6 months of life, suggesting mild cognitive impairment-like manifestations before general learning/memory impairments emerged at an older age. Interestingly, all of these features were present in 3xTg-AD mice prior to significant amyloid-β or tau pathology. Conclusion The results indicate that behavioral deficits in AD mice develop in parallel with systemic autoimmune/inflammatory disease. These changes antedate AD-like neuropathology, thus supporting a causal link between autoimmunity and aberrant behavior. Consequently, 3xTg-AD mice may be a useful model in elucidating the role of immune system in the etiology of AD.

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Section: Discussionsupporting

confidence: 88%

Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

Marchese

Cowan

Head

et al. 2014

JAD

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“…86, 87 Indeed, change in olfactory identification has been strongly associated with pathological changes in the medial temporal lobe structures. 88 These studies strongly imply a primary role for olfactory dysfunction as an indicator of pathological cognitive decline and dementia.…”

Section: Discussionmentioning

confidence: 99%

Olfactory discrimination predicts cognitive decline among community-dwelling older adults

et al. 2012

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The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46–86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio=0.869; P<0.05; 95% confidence interval=0.764−0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia.

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“…Some neuroimaging studies have examined the clinical and neuroanatomical correlates of olfactory performance in individuals with MCI and AD. Reduced olfactory identification was associated with smaller hippocampal volume in amnestic MCI and AD (Murphy et al, ; Lojkowska et al, ; Kjelvik et al, ). The 18 F‐fluorodeoxyglucose (FDG) PET study showed a relationship between olfactory identification score and FDG uptake in early AD (Forster et al, ), and associations between the olfactory tract integrity and metabolic activity in medial temporal lobe and posterior cortical structures in MCI (Cross et al, ).…”

Section: Discussionmentioning

confidence: 99%

Olfactory identification and white matter integrity in amnestic mild cognitive impairment: A preliminary study

Ryu

Lee

et al. 2016

Int. J. Imaging Syst. Technol.

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Increasing evidence suggests that olfactory impairment is associated with an increased risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease. This study was to explore how olfactory identification relates to white matter (WM) integrity, using diffusion tensor imaging (DTI) in individuals with amnestic MCI. DTI was performed from nineteen individuals with amnestic MCI (mean age: 69.95 6 8.20 years). Olfactory identification was assessed using the Cross-Cultural Smell Identification Test (CC-SIT), a widely used test for odor identification involving a scratch and sniff test of 12 micro-encapsulated odorants. Cross-sectional voxel-wise analyses of relationships between CC-SIT scores and DTI indices were performed using Tract-Based Spatial Statistics. Higher CC-SIT scores were associated with lower mean, axial and radial diffusivities in areas such as the body and splenium of corpus callosum, frontal WM (lateral orbitofrontal, caudal middle frontal, precentral, left superior frontal, and right pars opercularis), right superior longitudinal fasciculus, anterior and superior corona radiata, and internal and external capsules, while CC-SIT scores were not significantly associated with fractional anisotropy across all MCI participants. In individuals with amnestic MCI, impaired olfactory identification is associated with alterations in WM integrity expressed as a lower diffusivities value. This cross-sectional preliminary study suggests that olfactory impairment contributes to WM microstructural alterations in individuals with amnestic MCI.

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Follow-Up Study of Olfactory Deficits, Cognitive Functions, and Volume Loss of Medial Temporal Lobe Structures in Patients with Mild Cognitive Impairment

Abstract: Prediction of MCI to dementia conversion can be improved by supplementing the neuropsychological tests with odor identification tests. A follow up study of hippocampus volume reduction, OI performance and cognitive functions deterioration will further increase prediction accuracy.

Cited by 33 publications

References 0 publications

Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

Olfactory discrimination predicts cognitive decline among community-dwelling older adults

Olfactory identification and white matter integrity in amnestic mild cognitive impairment: A preliminary study

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