Odor identification deficit in mild cognitive impairment and Alzheimer's disease is associated with hippocampal and deep gray matter atrophy

Hagemeier, Jesper; Woodward, Matthew R.; Rafique, Usama; Amrutkar, Chaitanya; Bergsland, Niels; Dwyer, Michael G.; Benedict, Ralph H. B.; Zivadinov, Robert; Szigeti, Kinga

doi:10.1016/j.pscychresns.2016.08.003

Cited by 46 publications

(42 citation statements)

References 36 publications

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“…Third, we found some evidence for the levels of neuropsychological performance distinguishing the sub-groups based on experimental tasks to be mirrored in the children's levels of ADHD symptoms, (questionnaire-based) EF behavior, and odor identification ability. Olfactory function has been proposed as a biological marker for prefrontal, hippocampal, and dopaminergic function (Killgore et al 2008;Schecklmann et al 2011;Hagemeier et al 2016). Whereas odor identification logically did not differentiate between DA and EF in the present study as qualitatively distinct sub-groups were not found, children with lower levels of neuropsychological performance did identify fewer odors correctly than did children with higher levels.…”

Section: Discussioncontrasting

confidence: 82%

Are there distinct cognitive and motivational sub-groups of children with ADHD?

et al. 2017

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Section: Discussioncontrasting

confidence: 82%

Are there distinct cognitive and motivational sub-groups of children with ADHD?

et al. 2017

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“…Previous studies comparing methodologies similarly found better overlap between methods for hippocampal estimates than amygdala estimates (Morey et al, 2009). However, the discrepancies between manual segmentations and NeuroQuant segmentations are larger than previous investigations (Heckemann et al, 2006; Jatzko et al, 2006; Barnes et al, 2008; Powell et al, 2008; Aljabar et al, 2009; Artaechevarria et al, 2009; Morey et al, 2009; Lehmann et al, 2010; Fellhauer et al, 2015), regardless of using an age-matched atlas for adolescents in NeuroQuant segmentations. The differences between methods may be due to many factors.…”

Section: Discussionmentioning

confidence: 65%

“…Studies have compared automated segmentation and manual tracing of brain structures (Heckemann et al, 2006; Jatzko et al, 2006; Han and Fischl, 2007; Barnes et al, 2008; Powell et al, 2008; Aljabar et al, 2009; Artaechevarria et al, 2009; Fellhauer et al, 2015). These comparison studies use manual segmentation as a reference and validate the automated techniques based on the manually segmented volumes.…”

Section: Introductionmentioning

confidence: 99%

Associations between Family Adversity and Brain Volume in Adolescence: Manual vs. Automated Brain Segmentation Yields Different Results

et al. 2016

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Associations between brain structure and early adversity have been inconsistent in the literature. These inconsistencies may be partially due to methodological differences. Different methods of brain segmentation may produce different results, obscuring the relationship between early adversity and brain volume. Moreover, adolescence is a time of significant brain growth and certain brain areas have distinct rates of development, which may compromise the accuracy of automated segmentation approaches. In the current study, 23 adolescents participated in two waves of a longitudinal study. Family aggression was measured when the youths were 12 years old, and structural scans were acquired an average of 4 years later. Bilateral amygdalae and hippocampi were segmented using three different methods (manual tracing, FSL, and NeuroQuant). The segmentation estimates were compared, and linear regressions were run to assess the relationship between early family aggression exposure and all three volume segmentation estimates. Manual tracing results showed a positive relationship between family aggression and right amygdala volume, whereas FSL segmentation showed negative relationships between family aggression and both the left and right hippocampi. However, results indicate poor overlap between methods, and different associations were found between early family aggression exposure and brain volume depending on the segmentation method used.

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“… 5 Reduced structural integrity of brain regions that subserve olfaction appears especially vulnerable to such pathology. These changes include reduced entorhinal cortical thickness and hippocampus and amygdala volumes, 6 , 16 , 28 as well as fibrillar amyloid accumulation in the posterior cingulate, temporoparietal, and lingual cortical regions. 6 , 29 Data from 15 O-H 2 O-PET experiments on olfactory-evoked regional cerebral blood flow also demonstrate that patients with AD have a pattern of functional activation different from healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Odor identification as a biomarker of preclinical AD in older adults at risk

Lafaille‐Magnan¹,

Poirier²,

Étienne³

et al. 2017

Neurology

108

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Objective:To assess odor identification (OI) as an indicator of presymptomatic Alzheimer disease (AD) pathogenesis in cognitively normal aging individuals at increased risk of AD dementia.Methods:In 274 members of the PREVENT-AD cohort of healthy aging persons with a parental or multiple-sibling history of AD dementia, we assessed the cross-sectional association of OI with potential indicators of presymptomatic AD. Some 101 participants donated CSF, thus enabling assessment of AD pathology with the biomarkers total tau (t-tau), phospho-tau (P181-tau), and their ratios with β-amyloid (Aβ1-42). Adjusted analyses considered age, cognition, APOE ε4 status, education, and sex as covariates. We measured OI using the University of Pennsylvania Smell Identification Test and cognitive performance using the Repeatable Battery for Assessment of Neuropsychological Status. Standard kits provided assays of the AD biomarkers. Analyses used robust-fit linear regression models.Results:Reduced OI was associated with lower cognitive score and older age, as well as increased ratios of CSF t-tau and P181-tau to Aβ1-42 (all p < 0.02). However, the observed associations of OI with age and cognition were unapparent in adjusted models that restricted observations to CSF donors and included AD biomarkers. OI showed little association with CSF Aβ1-42 alone except in APOE ε4 carriers having lowest-quartile Aβ1-42 levels.Conclusions:These findings from healthy high-risk older individuals suggest that OI reflects degree of preclinical AD pathology, while its relationships with age and cognition result from the association of these latter variables with such pathology. Diminished OI may be a practical and affordable biomarker of AD pathology.

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Odor identification deficit in mild cognitive impairment and Alzheimer's disease is associated with hippocampal and deep gray matter atrophy

Cited by 46 publications

References 36 publications

Are there distinct cognitive and motivational sub-groups of children with ADHD?

Are there distinct cognitive and motivational sub-groups of children with ADHD?

Associations between Family Adversity and Brain Volume in Adolescence: Manual vs. Automated Brain Segmentation Yields Different Results

Odor identification as a biomarker of preclinical AD in older adults at risk

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