Odor Identification and Regional Gray Matter Atrophy in Patients with Alzheimer’s Disease, Parkinson’s Disease, and the Healthy Elderly: A Cross-Sectional Structural MRI Study

Abstract

Multiple associations between impaired olfactory performance and regional cortical and deep gray matter atrophy have been reported in separate studies of patients with Alzheimer’s disease (AD), Parkinson’s disease (PD), and of the healthy elderly. We aimed to evaluate such possible associations among these populations in a unified manner. Twenty AD, twenty PD patients’ and twenty healthy age- and sex-matched controls’ odor identification performance was assessed with the Lithuanian adaptation of the Sniffin’ Sticks 12 odor identification test, followed by morphometric gray matter analysis by MRI using FreeSurfer. AD patients had significantly lower cognitive performance than both PD patients and the healthy elderly, as evaluated with the Mini-Mental State Examination (MMSE). Odor identification performance was significantly worse in AD and PD patients compared with the healthy elderly; AD patients performed slightly worse than PD patients, but the difference was not statistically significant. Among patients with AD, worse odor identification performance was initially correlated with atrophy of multiple cortical and deep gray matter regions known to be involved in olfactory processing, however, only two measures—decreased thicknesses of the right medial and left lateral orbitofrontal cortices—remained significant after adjustment for possible confounders (age, MMSE score, and global cortical thickness). Among patients with PD and the healthy elderly we found no similar statistically significant correlations. Our findings support the key role of the orbitofrontal cortex in odor identification among patients with AD, and suggest that correlations between impaired odor identification performance and regional gray matter atrophy may be relatively more pronounced in AD rather than in PD.

Disparity of smell tests in Alzheimer’s disease and other neurodegenerative disorders: a systematic review and meta-analysis

“…The pooled data from two studies comparing olfactory identification scores in AD patients and PD patients revealed a non-significant difference in these scores between the two groups in all tests (k = 2; d = −0.40; 95%CI −0.82 to 0.02; Figure 6B ; Doty et al, 1991 ; Jesmanas et al, 2021 ). Low heterogeneity was found across studies (Q = 0.54; p = 0.46; I 2 < 0.01%).…”

“…Later 95 articles were excluded for the following reasons: they only had comparisons with healthy controls ( n = 12); lack of olfactory assessment methods ( n = 4); required data was not available ( n = 75) and patients in AD group had comorbidity with other neurodegenerative conditions ( n = 6). Consequently, 47 articles were considered eligible and 42 articles were included in the meta-analysis ( Doty et al, 1991 ; Solomon et al, 1998 ; McCaffrey et al, 2000 ; Duff et al, 2002 ; Peters et al, 2003 ; Westervelt et al, 2003 ; Tabert et al, 2005 ; Motomura and Tomota, 2006 ; Pentzek et al, 2007 ; Djordjevic et al, 2008 ; McLaughlin and Westervelt, 2008 ; Westervelt et al, 2008 ; Williams et al, 2009 ; Bahar-Fuchs et al, 2010 ; Steinbach et al, 2010 ; Bahar-Fuchs et al, 2011 ; Sato et al, 2011 ; Tkalčić et al, 2011 ; Seligman et al, 2013 ; Körtvélyessy et al, 2015 ; Westervelt et al, 2016 ; Quarmley et al, 2017 ; Reijs et al, 2017 ; Umeda-Kameyama et al, 2017 ; Vasavada et al, 2017 ; Ward et al, 2017 ; Woodward et al, 2017 ; Yoo and Ye, 2017 ; Chen et al, 2018 ; Doorduijn et al, 2018 ; Woodward et al, 2018 ; Yoo et al, 2018 ; Wu et al, 2019 ; Yoshii et al, 2019 ; Bathini et al, 2020 ; Forsberg et al, 2021 ; Inagawa et al, 2020 ; Kim et al, 2020 ; Zhao et al, 2020 ; Jesmanas et al, 2021 ; Wang et al, 2021 ; Chen et al, 2022 ), since only one article was included in five disease types and one olfactory task, which was insufficient for the meta-analysis ( Moberg et al, 1997 ; Luzzi et al, 2007 ; Naudin et al, 2014 ; Passler et al, 2017 ; Sun...…”

“…Most smell tests in this meta-analysis were for olfactory identification. These olfactory identification tests included the University of Pennsylvania Smell Identification Test (UPSIT) which consisted of 40-item version ( n = 10; Doty et al, 1991 ; Tabert et al, 2005 ; Motomura and Tomota, 2006 ; Djordjevic et al, 2008 ; Vasavada et al, 2017 ; Ward et al, 2017 ; Woodward et al, 2017 , 2018 ; Wu et al, 2019 ; Bathini et al, 2020 ) and 10-item version ( n = 2; Bahar-Fuchs et al, 2010 , 2011 ), the Sniffin’ Sticks test (SS) which consisted SS-16 version ( n = 10; Pentzek et al, 2007 ; Williams et al, 2009 ; Steinbach et al, 2010 ; Seligman et al, 2013 ; Quarmley et al, 2017 ; Chen et al, 2018 ; Doorduijn et al, 2018 ; Zhao et al, 2020 ; Wang et al, 2021 ; Chen et al, 2022 ) and SS-12 version ( n = 2; Körtvélyessy et al, 2015 ; Jesmanas et al, 2021 ), the Cross-Cultural Smell Identification Test (CCSIT) which was also known as the Brief Smell Identification Test (B-SIT, n = 8; Westervelt et al, 2003 , 2008 , 2016 ; McLaughlin and Westervelt, 2008 ; Reijs et al, 2017 ; Yoo and Ye, 2017 ; Yoo et al, 2018 ; Forsberg et al, 2021 ), the Odor Stick Identification Test for Japanese (OSIT-J, n = 3; Umeda-Kameyama et al, 2017 ; Yoshii et al, 2019 ; Inagawa et al, 2020 ), the Pocket Smell Test (PST, n = 3; Solomon et al, 1998 ; McCaffrey et al, 2000 ; Duff et al, 2002 ), the Open Essence Smell Identification test ( n = 1; Sato et al, 2011 ), the Scandinavian Odor Identification Test (S-OIT, n = 1; Tkalčić et al, 2011 ), the YSK olfactory function test ( n = 1; Kim et al, 2020 ) and the common odors (16 items; n = 1; Peters et al, 2003 ). The N-butanol alcohol test, Sniffn’ Sticks test and the YSK olfa...…”

“…There were 42 studies with sufficient information to calculate effect size in the meta-analysis ( Doty et al, 1991 ; Solomon et al, 1998 ; McCaffrey et al, 2000 ; Duff et al, 2002 ; Peters et al, 2003 ; Westervelt et al, 2003 ; Tabert et al, 2005 ; Motomura and Tomota, 2006 ; Pentzek et al, 2007 ; Djordjevic et al, 2008 ; McLaughlin and Westervelt, 2008 ; Westervelt et al, 2008 ; Williams et al, 2009 ; Bahar-Fuchs et al, 2010 ; Steinbach et al, 2010 ; Bahar-Fuchs et al, 2011 ; Sato et al, 2011 ; Tkalčić et al, 2011 ; Seligman et al, 2013 ; Körtvélyessy et al, 2015 ; Westervelt et al, 2016 ; Quarmley et al, 2017 ; Reijs et al, 2017 ; Umeda-Kameyama et al, 2017 ; Vasavada et al, 2017 ; Ward et al, 2017 ; Woodward et al, 2017 ; Yoo and Ye, 2017 ; Chen et al, 2018 ; Doorduijn et al, 2018 ; Woodward et al, 2018 ; Yoo et al, 2018 ; Wu et al, 2019 ; Yoshii et al, 2019 ; Bathini et al, 2020 ; Forsberg et al, 2021 ; Inagawa et al, 2020 ; Kim et al, 2020 ; Zhao et al, 2020 ; Jesmanas et al, 2021 ; Wang et al, 2021 ; Chen et al, 2022 ). All studies except one compared AD with one specific disease by smell tests, while the remaining study tested AD patients, VaD patients, and individuals with depression simultaneously ( Duff et al, 2002 ).…”

“…The meta-analyses were conducted in comparison of AD with seven conditions separately, including MCI ( n = 23), LBD ( n = 8), depression ( n = 5), VaD ( n = 3), PD ( n = 2), and FTD ( n = 2). Most studies examined the olfactory identification function ( Doty et al, 1991 ; Solomon et al, 1998 ; McCaffrey et al, 2000 ; Duff et al, 2002 ; Peters et al, 2003 ; Westervelt et al, 2003 ; Tabert et al, 2005 ; Motomura and Tomota, 2006 ; Pentzek et al, 2007 ; Djordjevic et al, 2008 ; McLaughlin and Westervelt, 2008 ; Westervelt et al, 2008 ; Williams et al, 2009 ; Bahar-Fuchs et al, 2010 ; Steinbach et al, 2010 ; Bahar-Fuchs et al, 2011 ; Sato et al, 2011 ; Tkalčić et al, 2011 ; Seligman et al, 2013 ; Körtvélyessy et al, 2015 ; Westervelt et al, 2016 ; Quarmley et al, 2017 ; Reijs et al, 2017 ; Umeda-Kameyama et al, 2017 ; Vasavada et al, 2017 ; Ward et al, 2017 ; Woodward et al, 2017 ; Yoo and Ye, 2017 ; Chen et al, 2018 ; Doorduijn et al, 2018 ; Woodward et al, 2018 ; Yoo et al, 2018 ; Wu et al, 2019 ; Yoshii et al, 2019 ; Bathini et al, 2020 ; Forsberg et al, 2021 ; Inagawa et al, 2020 ; Kim et al, 2020 ; Zhao et al, 2020 ; Jesmanas et al, 2021 ; Wang et al, 2021 ; Chen et al, 2022 ), while the olfactory threshold function was examined in the AD vs. MCI ( Peters et al, 2003 ; Steinbach et al, 2010 ; Doorduijn et al, 2018 ; Kim et al, 2020 ), while the olfactory discrimination function was examined in the AD vs. MCI group ( Peters et al, 2003 ; Djordjevic et al, 2...…”