Clinical and Neuropsychological Differences between Mild Parkinson's Disease Dementia and Dementia with Lewy Bodies
Identifieur interne : 000013 ( Pmc/Curation ); précédent : 000012; suivant : 000014Clinical and Neuropsychological Differences between Mild Parkinson's Disease Dementia and Dementia with Lewy Bodies
Auteurs : Mariya Petrova [Bulgarie] ; Shima Mehrabian [Bulgarie] ; Dag Aarsland [Suède, Norvège] ; Margarita Raycheva [Bulgarie] ; Latchezar Traykov [Bulgarie]Source :
- Dementia and Geriatric Cognitive Disorders EXTRA [ 1664-5464 ] ; 2015.
Abstract
The specific profile of dementia in Parkinson's disease (PDD) and dementia with Lewy bodies (DLB) in the earliest stages of dementia is still unclear and subject of considerable controversy.
We investigated 27 PDD patients and 24 DLB patients with parkinsonism in the early stage of dementia, i.e. with a Mini-Mental State Examination score of ≥24.
Compared to PDD, patients with DLB demonstrated significantly lower scores when testing attention and executive functions [modified card sorting test (p < 0.001) and digit span backward (p < 0.02)], as well as when testing constructive abilities [copy of complex designs (p = 0.001) and pentagon (p < 0.001)]. Using logistic regression analysis, diagnosis was predicted from the cognitive profile, with an overall accuracy of 88.2%. In addition, PDD patients showed a significantly higher Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore (p < 0.001) as well as higher UPDRS motor item scores [tremor at rest (p = 0.01) and bradykinesia (p = 0.001)].
The cognitive profile in PDD differs from that in DLB in the early stage of dementia, with worse performance on tests of attention and executive functions and constructive abilities in DLB compared to PDD patients. In contrast, motor symptoms are more severe in PDD than in DLB.
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DOI: 10.1159/000375363
PubMed: 26195977
PubMed Central: 4483490
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Clinical and Neuropsychological Differences between Mild Parkinson's Disease Dementia and Dementia with Lewy Bodies</title><author><name sortKey="Petrova, Mariya" sort="Petrova, Mariya" uniqKey="Petrova M" first="Mariya" last="Petrova">Mariya Petrova</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Neurology, University Hospital ‘Alexandrovska’, Sofia, Bulgaria</nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea>Department of Neurology, University Hospital ‘Alexandrovska’, Sofia</wicri:regionArea></affiliation></author><author><name sortKey="Mehrabian Spasova, Shima" sort="Mehrabian Spasova, Shima" uniqKey="Mehrabian Spasova S" first="Shima" last="Mehrabian">Shima Mehrabian</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Neurology, University Hospital ‘Alexandrovska’, Sofia, Bulgaria</nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea>Department of Neurology, University Hospital ‘Alexandrovska’, Sofia</wicri:regionArea></affiliation></author><author><name sortKey="Aarsland, Dag" sort="Aarsland, Dag" uniqKey="Aarsland D" first="Dag" last="Aarsland">Dag Aarsland</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger</wicri:regionArea></affiliation></author><author><name sortKey="Raycheva, Margarita" sort="Raycheva, Margarita" uniqKey="Raycheva M" first="Margarita" last="Raycheva">Margarita Raycheva</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Neurology, University Hospital ‘Alexandrovska’, Sofia, Bulgaria</nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea>Department of Neurology, University Hospital ‘Alexandrovska’, Sofia</wicri:regionArea></affiliation></author><author><name sortKey="Traykov, Latchezar" sort="Traykov, Latchezar" uniqKey="Traykov L" first="Latchezar" last="Traykov">Latchezar Traykov</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Neurology, University Hospital ‘Alexandrovska’, Sofia, Bulgaria</nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea>Department of Neurology, University Hospital ‘Alexandrovska’, Sofia</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26195977</idno><idno type="pmc">4483490</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483490</idno><idno type="RBID">PMC:4483490</idno><idno type="doi">10.1159/000375363</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000013</idno><idno type="wicri:Area/Pmc/Curation">000013</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Clinical and Neuropsychological Differences between Mild Parkinson's Disease Dementia and Dementia with Lewy Bodies</title><author><name sortKey="Petrova, Mariya" sort="Petrova, Mariya" uniqKey="Petrova M" first="Mariya" last="Petrova">Mariya Petrova</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Neurology, University Hospital ‘Alexandrovska’, Sofia, Bulgaria</nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea>Department of Neurology, University Hospital ‘Alexandrovska’, Sofia</wicri:regionArea></affiliation></author><author><name sortKey="Mehrabian Spasova, Shima" sort="Mehrabian Spasova, Shima" uniqKey="Mehrabian Spasova S" first="Shima" last="Mehrabian">Shima Mehrabian</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Neurology, University Hospital ‘Alexandrovska’, Sofia, Bulgaria</nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea>Department of Neurology, University Hospital ‘Alexandrovska’, Sofia</wicri:regionArea></affiliation></author><author><name sortKey="Aarsland, Dag" sort="Aarsland, Dag" uniqKey="Aarsland D" first="Dag" last="Aarsland">Dag Aarsland</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger</wicri:regionArea></affiliation></author><author><name sortKey="Raycheva, Margarita" sort="Raycheva, Margarita" uniqKey="Raycheva M" first="Margarita" last="Raycheva">Margarita Raycheva</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Neurology, University Hospital ‘Alexandrovska’, Sofia, Bulgaria</nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea>Department of Neurology, University Hospital ‘Alexandrovska’, Sofia</wicri:regionArea></affiliation></author><author><name sortKey="Traykov, Latchezar" sort="Traykov, Latchezar" uniqKey="Traykov L" first="Latchezar" last="Traykov">Latchezar Traykov</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Neurology, University Hospital ‘Alexandrovska’, Sofia, Bulgaria</nlm:aff><country xml:lang="fr">Bulgarie</country><wicri:regionArea>Department of Neurology, University Hospital ‘Alexandrovska’, Sofia</wicri:regionArea></affiliation></author></analytic><series><title level="j">Dementia and Geriatric Cognitive Disorders EXTRA</title><idno type="ISSN">1664-5464</idno><idno type="e-ISSN">1664-5464</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>The specific profile of dementia in Parkinson's disease (PDD) and dementia with Lewy bodies (DLB) in the earliest stages of dementia is still unclear and subject of considerable controversy.</p></sec><sec><title>Methods</title><p>We investigated 27 PDD patients and 24 DLB patients with parkinsonism in the early stage of dementia, i.e. with a Mini-Mental State Examination score of ≥24.</p></sec><sec><title>Results</title><p>Compared to PDD, patients with DLB demonstrated significantly lower scores when testing attention and executive functions [modified card sorting test (p < 0.001) and digit span backward (p < 0.02)], as well as when testing constructive abilities [copy of complex designs (p = 0.001) and pentagon (p < 0.001)]. Using logistic regression analysis, diagnosis was predicted from the cognitive profile, with an overall accuracy of 88.2%. In addition, PDD patients showed a significantly higher Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore (p < 0.001) as well as higher UPDRS motor item scores [tremor at rest (p = 0.01) and bradykinesia (p = 0.001)].</p></sec><sec><title>Conclusions</title><p>The cognitive profile in PDD differs from that in DLB in the early stage of dementia, with worse performance on tests of attention and executive functions and constructive abilities in DLB compared to PDD patients. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Dement Geriatr Cogn Dis Extra</journal-id><journal-id journal-id-type="iso-abbrev">Dement Geriatr Cogn Dis Extra</journal-id><journal-id journal-id-type="publisher-id">DEE</journal-id><journal-title-group><journal-title>Dementia and Geriatric Cognitive Disorders EXTRA</journal-title></journal-title-group><issn pub-type="ppub">1664-5464</issn><issn pub-type="epub">1664-5464</issn><publisher><publisher-name>S. Karger AG</publisher-name><publisher-loc>Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.ch</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26195977</article-id><article-id pub-id-type="pmc">4483490</article-id><article-id pub-id-type="doi">10.1159/000375363</article-id><article-id pub-id-type="publisher-id">dee-0005-0212</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Research Article</subject></subj-group></article-categories><title-group><article-title>Clinical and Neuropsychological Differences between Mild Parkinson's Disease Dementia and Dementia with Lewy Bodies</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Petrova</surname><given-names>Mariya</given-names></name><xref ref-type="aff" rid="aff1">a</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>Mehrabian-Spasova</surname><given-names>Shima</given-names></name><xref ref-type="aff" rid="aff1">a</xref></contrib><contrib contrib-type="author"><name><surname>Aarsland</surname><given-names>Dag</given-names></name><xref ref-type="aff" rid="aff2">b</xref><xref ref-type="aff" rid="aff3">c</xref></contrib><contrib contrib-type="author"><name><surname>Raycheva</surname><given-names>Margarita</given-names></name><xref ref-type="aff" rid="aff1">a</xref></contrib><contrib contrib-type="author"><name><surname>Traykov</surname><given-names>Latchezar</given-names></name><xref ref-type="aff" rid="aff1">a</xref></contrib></contrib-group><aff id="aff1"><sup>a</sup>Department of Neurology, University Hospital ‘Alexandrovska’, Sofia, Bulgaria</aff><aff id="aff2"><sup>b</sup>Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden</aff><aff id="aff3"><sup>c</sup>Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway</aff><author-notes><corresp id="cor1">*Mariya Petrova, MD, PhD, Department of Neurology, University Hospital ‘Alexandrovska’, 1 Georgi Sofiiski street, BG-1431 Sofia (Bulgaria), E-Mail <email>dr.mpetrova@mail.bg</email></corresp></author-notes><pub-date pub-type="collection"><season>May-Aug</season><year>2015</year></pub-date><pub-date pub-type="epub"><day>29</day><month>5</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>29</day><month>5</month><year>2015</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>5</volume><issue>2</issue><fpage>212</fpage><lpage>220</lpage><permissions><copyright-statement>Copyright © 2015 by S. Karger AG, Basel</copyright-statement><copyright-year>2015</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/"><license-p>This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.</license-p></license></permissions><abstract><sec><title>Background</title><p>The specific profile of dementia in Parkinson's disease (PDD) and dementia with Lewy bodies (DLB) in the earliest stages of dementia is still unclear and subject of considerable controversy.</p></sec><sec><title>Methods</title><p>We investigated 27 PDD patients and 24 DLB patients with parkinsonism in the early stage of dementia, i.e. with a Mini-Mental State Examination score of ≥24.</p></sec><sec><title>Results</title><p>Compared to PDD, patients with DLB demonstrated significantly lower scores when testing attention and executive functions [modified card sorting test (p < 0.001) and digit span backward (p < 0.02)], as well as when testing constructive abilities [copy of complex designs (p = 0.001) and pentagon (p < 0.001)]. Using logistic regression analysis, diagnosis was predicted from the cognitive profile, with an overall accuracy of 88.2%. In addition, PDD patients showed a significantly higher Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore (p < 0.001) as well as higher UPDRS motor item scores [tremor at rest (p = 0.01) and bradykinesia (p = 0.001)].</p></sec><sec><title>Conclusions</title><p>The cognitive profile in PDD differs from that in DLB in the early stage of dementia, with worse performance on tests of attention and executive functions and constructive abilities in DLB compared to PDD patients. In contrast, motor symptoms are more severe in PDD than in DLB.</p></sec></abstract><kwd-group><title>Key Words</title><kwd>Parkinson's disease</kwd><kwd>Mild dementia</kwd><kwd>Dementia with Lewy bodies</kwd><kwd>Clinical presentation</kwd></kwd-group><counts><table-count count="2"></table-count><ref-count count="43"></ref-count><page-count count="9"></page-count></counts></article-meta></front><body><sec sec-type="intro" id="sec1_1"><title>Introduction</title><p>The prevalence of dementia in Parkinson's disease (PDD) is close to 30%, and at least 75% of Parkinson's disease (PD) patients who survive for more than 10 years will develop dementia [<xref rid="B1" ref-type="bibr">1</xref>,<xref rid="B2" ref-type="bibr">2</xref>].</p><p>The dementia of PD often closely resembles dementia with Lewy bodies (DLB), with fluctuating cognition and visual hallucinations. Current consensus criteria suggest that a differentiation should be made between DLB and PDD on the basis of the duration of extrapyramidal signs prior to the onset of dementia [<xref rid="B3" ref-type="bibr">3</xref>]. The diagnostic label of PDD is reserved for patients who have had motor symptoms only for at least 12 months before the onset of dementia. The cognitive profile and parkinsonism in DLB and PDD are similar, although some differences have been noticed [<xref rid="B4" ref-type="bibr">4</xref>,<xref rid="B5" ref-type="bibr">5</xref>,<xref rid="B6" ref-type="bibr">6</xref>,<xref rid="B7" ref-type="bibr">7</xref>].</p><p>Recently, the Movement Disorder Society Task Force has proposed to revise criteria for PD, such that patients who present with motor signs should be diagnosed with PD even in the presence of dementia [<xref rid="B8" ref-type="bibr">8</xref>]. The Task Force raises the question whether the diagnosis of PD should or should not depend on the presence (or timing) of dementia. If the diagnosis of PD did not depend on the presence of dementia, similar profiles of PDD and DLB could be expected, especially in the early stage of dementia. However, such changes should be underpinned by solid evidence.</p><p>Therefore, we compared the clinical and neuropsychological profiles of patients with DLB and PDD. In contrast to most previous studies, which were based on patients with moderately severe dementia [<xref rid="B5" ref-type="bibr">5</xref>,<xref rid="B6" ref-type="bibr">6</xref>,<xref rid="B9" ref-type="bibr">9</xref>,<xref rid="B10" ref-type="bibr">10</xref>,<xref rid="B11" ref-type="bibr">11</xref>,<xref rid="B12" ref-type="bibr">12</xref>], we included patients with mild or very mild dementia, which is relevant given the increased focus on the early stages of neurodegenerative diseases.</p></sec><sec sec-type="methods" id="sec1_2"><title>Methods</title><sec id="sec2_1"><title>Participants</title><p>Patients were selected from subjects who sought consultation at the Department of Neurology, University Hospital ‘Alexandrovska’, Sofia, Bulgaria. Patients presented with cognitive and/or motor complaints or were in the advanced stage of PD requiring hospitalization. The research was approved by the local ethics committee, and all subjects signed informed consent. The evaluation process comprised a detailed medical history (from patients, family members and medical records), physical and neurological examinations, cognitive evaluations, appropriate laboratory tests and neuroimaging. Psychiatric evaluation included a semistructured interview and the Geriatric Depression Scale [<xref rid="B13" ref-type="bibr">13</xref>]. Exclusion criteria were clinically relevant cerebrovascular disease, uncorrected visual deficit as well as evidence of causes for dementia such as vitamin B<sub>12</sub> deficiency, folic acid deficiency, thyroid dysfunction or head trauma. None of the patients were tested during a period of episodic confusion. We also excluded patients if the time of onset of dementia relative to parkinsonism was unclear.</p><p>For the diagnosis and staging of dementia in both groups, we used the following neuropsychological tests: Mini-Mental State Examination (MMSE) [<xref rid="B14" ref-type="bibr">14</xref>], Mini-Mental Parkinson (MMP) [<xref rid="B15" ref-type="bibr">15</xref>] and Dementia Rating Scale [<xref rid="B16" ref-type="bibr">16</xref>]. We used an MMSE score of ≥24 to categorize mild PDD and DLB, as is often used in Alzheimer's disease [<xref rid="B17" ref-type="bibr">17</xref>,<xref rid="B18" ref-type="bibr">18</xref>], PD [<xref rid="B19" ref-type="bibr">19</xref>,<xref rid="B20" ref-type="bibr">20</xref>] and DLB [<xref rid="B21" ref-type="bibr">21</xref>].</p><p>The evaluation of activities of daily living, including the abilities to manage personal finances, use the telephone, take care of all shopping needs, use public transportation, take medications and cope in social situations, was based on the interview with the patients and their caregivers. The relative contribution of motor versus cognitive impairment to activities of daily living performance was determined by the clinicians at the time of the interview. The impact of cognitive impairment on daily living was considered significant when the patient showed deterioration in more than one daily activity, i.e. dementia, which was a requirement for inclusion. All DLB patients examined in this study had parkinsonism at the time of examination, which was also required for inclusion and was based on the judgment of a neurologist with experience in movement disorders.</p></sec><sec id="sec2_2"><title>Dementia with Lewy Bodies</title><p>Diagnosis was based on the modified DLB Consortium criteria for DLB [<xref rid="B3" ref-type="bibr">3</xref>]. DLB was diagnosed when dementia occurred before, concurrently or within 1 year after the onset of parkinsonism. Of the 24 DLB patients, 21 had probable DLB according to consensus criteria at the time of testing, i.e. had at least one core feature in addition to parkinsonism: visual hallucinations (2 patients), cognitive fluctuations (11 patients), visual hallucinations and cognitive fluctuations (5 patients) or parkinsonism and one suggestive feature (3 patients). The remaining 3 DLB patients had possible DLB (i.e. parkinsonism and mild dementia) at initial evaluation but developed visual hallucinations and cognitive fluctuations during the first year after the baseline evaluation. Fluctuating cognition was rated as present when the caregiver gave positive answers to one or both questions about ‘fluctuating confusion’ or ‘impaired consciousness’ using the Clinical Assessment of Fluctuation Scale [<xref rid="B22" ref-type="bibr">22</xref>].</p></sec><sec id="sec2_3"><title>Dementia in Parkinson's Disease</title><p>The diagnosis of PDD was made based on the Movement Disorder Society Task Force criteria for dementia [<xref rid="B23" ref-type="bibr">23</xref>]. The onset of established PD (UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria for PD [<xref rid="B24" ref-type="bibr">24</xref>]) preceded the development of dementia by at least 12 months. In this study, the time of onset of dementia in PDD patients was at least 4 years after the diagnosis of PD. To ensure that any differences in group test profiles could be attributed to differences in the underlying nature of the disorders rather than to differences in age, educational level and/or global level of dementia, we selected 27 patients from a large cohort of 86 PDD patients, who matched a DLB patient with regard to age, education and Mini Mental Parkinson.</p></sec><sec id="sec2_4"><title>Neuropsychological Assessment</title><p>Detailed cognitive evaluation of both groups included a neuropsychological battery. <italic>Episodic memory</italic> was assessed with the Buschke Free and Cued Selective Reminding Test [<xref rid="B25" ref-type="bibr">25</xref>]. <italic>Attention and executive functions</italic> were tested by the Trail Making Test part A and B [<xref rid="B26" ref-type="bibr">26</xref>], the Modified Card Sorting Test (MCST) [<xref rid="B27" ref-type="bibr">27</xref>], digit span backward of the Wechsler Adult Intelligence Scale [<xref rid="B28" ref-type="bibr">28</xref>] and the Stroop Test [<xref rid="B29" ref-type="bibr">29</xref>]. <italic>Language abilities</italic> were determined by the 15-item subset of the Boston Naming Test [<xref rid="B30" ref-type="bibr">30</xref>], the semantic verbal fluency and the phonemic verbal fluency [<xref rid="B31" ref-type="bibr">31</xref>]. <italic>Visuospatial abilities</italic> and constructional praxis were evaluated by the Clock Drawing Test [<xref rid="B32" ref-type="bibr">32</xref>], the ability to copy 5 complex designs [<xref rid="B33" ref-type="bibr">33</xref>] and the interlocking pentagon copying item within the MMSE [<xref rid="B34" ref-type="bibr">34</xref>].</p></sec><sec id="sec2_5"><title>Parkinsonism</title><p>The severity of parkinsonism in both patient groups was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) part III and IV [<xref rid="B35" ref-type="bibr">35</xref>], the Hoehn and Yahr staging [<xref rid="B36" ref-type="bibr">36</xref>] and the PD motor subtype according to the method suggested by Jankovic et al. [<xref rid="B37" ref-type="bibr">37</xref>]. All patients were evaluated in the off state.</p></sec><sec id="sec2_6"><title>Statistical Analysis</title><p>Not normally distributed data were analyzed using the Mann-Whitney test, normally distributed data were analyzed using Student's t test, and categorical data were analyzed using the χ<sup>2</sup> test. A statistical significance level of 0.05 was chosen for all analyses. Since this was an exploratory analysis, no formal attempt was made to adjust for multiple testing. Cognitive variables that were significantly associated with diagnosis in bivariate analysis were included as independent variables in a subsequent multivariate logistic regression model, using diagnosis as the dependent variable. Logistic regression analysis was used to investigate whether the diagnosis could be accurately predicted from the cognitive profile.</p></sec></sec><sec sec-type="results" id="sec1_3"><title>Results</title><sec id="sec2_7"><title>Demographic and Clinical Characteristics</title><p>The demographic and clinical characteristics of both groups are presented in table <xref ref-type="table" rid="T1">1</xref>. There were no significant intergroup differences regarding age, education, MMSE and MMP scores, and gender, as expected due to the matching procedure, but PDD patients showed a significantly longer disease duration than DLB patients.</p><p>Of the PDD patients, 6 had hallucinations at the time of testing (6 had visual hallucinations and 3 of them had additional auditory hallucinations), compared to 10 of the DLB patients (7 had visual hallucinations, 2 had auditory hallucinations, and 1 had other hallucinations).</p></sec><sec id="sec2_8"><title>Comparison of Motor Symptoms</title><p>On the Hoehn and Yahr scale as well as on UPDRS III (motor scale) and IV (motor fluctuations and dyskinesia), the PDD group had significantly higher scores than the DLB group, but there was no significant difference in predominant motor subtype between both groups. The tremor severity was higher in the PDD group, but only regarding the tremor at rest, which was marginally significant (p = 0.012). Compared to DLB patients, PDD patients also demonstrated a significantly higher score on hand and feet bradykinesia as well as a tendency towards increased rigidity.</p></sec><sec id="sec2_9"><title>Comparison of Neuropsychological Tests</title><p>The neuropsychological performances of both groups are demonstrated in table <xref ref-type="table" rid="T2">2</xref>. There were no significant group differences for the memory or language test scores.</p><p>The DLB group performed poorer than the PDD group on two of the three visuoconstructive tests. Among the attention/executive tests, the only difference was that DLB patients showed more perseverative errors on the MCST and a more significant impairment in digit span backward, although the latter was only marginally significant. On the Stroop Test, part 2 (p = 0.054) and 3, there were also trends towards poorer performance in the DLB group.</p><p>A binary logistic regression analysis showed that the full model with the four scores that differed between the groups was statistically significant (χ<sup>2</sup> = 0.994; d.f. 8; p = 0.000), indicating that the cognitive profile distinguished between DLB and PDD patients. The correct prediction of PDD and DLB was 88.9 and 87.5%, respectively, yielding an overall success rate of 88.2%. The strongest predictor of diagnostic category was the variable ‘pentagon drawing’ [B −1,503; Wald 5,907; d.f. 1; p = 0.015; OR 0.223 (95% CI 0.066-0.748)].</p></sec></sec><sec sec-type="discussion" id="sec1_4"><title>Discussion</title><p>The relationship between DLB and PDD is still unresolved, and there are both similarities and differences. Recently, it was suggested to classify DLB with parkinsonism as a subtype of PD [<xref rid="B8" ref-type="bibr">8</xref>]. However, more studies are needed to clarify this, and this is particularly true for the early disease stages.</p><sec id="sec2_10"><title>Major Findings of Present Work</title><p>In this study, we compared cognitive and motor symptoms of patients with mild DLB and PDD. The main finding was that DLB patients showed more attention/executive and visuoconstructive deficits as compared to PDD patients. The logistic regression analysis was able to correctly classify 88.2% of the patients with DLB or PDD, based on the cognitive profile. The strongest predictor of diagnostic category was the variable ‘pentagon drawing’. Additionally, PDD patients demonstrated more significant motor deterioration based mostly on dopaminergic symptoms (tremor at rest and bradykinesia) compared to DLB patients.</p></sec><sec id="sec2_11"><title>Deficits in Attention/Executive Functions</title><p>In the domain of attention/executive functions, DLB patients performed significantly worse on digit span backward and MCST (perseverative errors) than PDD patients. In 2014, Yoon et al. [<xref rid="B38" ref-type="bibr">38</xref>] also found that the attention/executive domain is more affected in DLB compared to PD even in the mild cognitive impairment stage. A recent neuroimaging study showed that numbers of categories achieved and perseverative errors in the Wisconsin Card Sorting Test should be differentially estimated, because they reflect the function of different brain regions in patients with early dementia [<xref rid="B39" ref-type="bibr">39</xref>], i.e. categories achieved mainly reflect the function of the precentral segments, whereas perseverative error scores correlate with metabolic activity in the right thalamus.</p></sec><sec id="sec2_12"><title>Deficits in Constructive Abilities</title><p>We also found that even patients with mild DLB are unable to cope with tasks which involve constructive abilities compared to patients with mild PDD. Cormack et al. [<xref rid="B9" ref-type="bibr">9</xref>] found a strong correlation between total MMSE and Cambridge Cognition Examination scores and pentagon copying in PDD patients, but not in patients with DLB. The authors suggested that in PDD, constructional disability appears to develop proportionately to a global cognitive impairment, whereas in DLB there is a selective impairment of constructional ability, above and beyond the global impairment. Several other authors also notice that the level of visuospatial impairment found in patients with DLB is disproportionately severe relative to the deficits that they exhibit in other cognitive domains [<xref rid="B4" ref-type="bibr">4</xref>,<xref rid="B40" ref-type="bibr">40</xref>]. A recent neuroimaging study showed that DLB patients exhibit more severe atrophy in parietal and occipital areas relative to those with PDD [<xref rid="B41" ref-type="bibr">41</xref>]. These data could explain the poorer visuospatial performance of DLB patients compared to PDD patients.</p></sec><sec id="sec2_13"><title>Severity of Parkinsonism</title><p>We found that patients with mild PDD have more significant motor deficit than DLB patients, which was mostly due to higher dopaminergic symptoms (tremor at rest and bradykinesia). Furthermore, resting tremor was more characteristic for PDD than for DLB patients, whereas the severity of postural and intention tremor was similar in both patient groups. Onofrj et al. [<xref rid="B42" ref-type="bibr">42</xref>] also concluded that tremor is common in DLB, and that the tremor in DLB patients presented a complex pattern of mixed tremors, characterized by rest and postural/action tremor. In vivo studies demonstrate that cell loss in the substantia nigra is less pronounced in DLB than in PD [<xref rid="B11" ref-type="bibr">11</xref>]. The underlying pathophysiology of impaired postural control in PD is complex, although the role of the pedunculopontine nucleus is the most emphasized in recent years [<xref rid="B43" ref-type="bibr">43</xref>]. In the present study, we did not find any significant difference in postural instabilities between the two groups; we could suggest that the cholinergic changes in the pedunculopontine nucleus are rather similar in PDD and DLB.</p></sec><sec id="sec2_14"><title>Study Limitations</title><p>Firstly, the lack of pathological confirmation of the clinical diagnosis represents a potential limitation in this study. However, we have employed the most recent clinical consensus criteria available at the time of the study for both disorders which were found to be more sensitive than previous criteria [<xref rid="B12" ref-type="bibr">12</xref>]. In addition, all PD patients and most of the DLB patients have been followed for at least 4 years without evidence of diagnoses other than PD and DLB. Secondly, the sample size was relatively small, and thus the statistical power to detect small effect sizes was low, with a risk for type 2 error. Finally, a number of comparisons were performed without adjusting for multiple testing. Thus, our findings should be interpreted with caution.</p></sec></sec><sec sec-type="conclusions" id="sec1_5"><title>Conclusions</title><p>In conclusion, the results of the current study indicate that patients with mild DLB and those with PDD exhibit a different cognitive symptom profile. In addition, at the mild dementia stage, motor symptoms are more advanced in PDD than in DLB. These differences likely reflect the heterogeneity of the underlying lesions in PD and DLB patients with mild dementia, i.e. more nigrostriatal pathological changes in PD and more cortical changes in DLB (Lewy bodies, amyloid plaques, vascular disease). Although the changes in motor profile could be related to different disease durations of the DLB and PD groups, it could not completely reflect differences in pathophysiology or pathology.</p><p>Future larger studies are needed, which take into account accompanying brain changes as well as the longitudinal course of the symptoms.</p></sec><sec id="sec1_6"><title>Disclosure Statement</title><p>The authors have no conflicts of interest to declare.</p></sec></body><back><ack><title>Acknowledgements</title><p>This work is supported by a grant from the Medical University Sofia, Bulgaria.</p></ack><ref-list><title>References</title><ref id="B1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aarsland</surname><given-names>D</given-names></name><name><surname>Zaccai</surname><given-names>J</given-names></name><name><surname>Brayne</surname><given-names>C</given-names></name></person-group><article-title>A systematic review 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id="T1" orientation="portrait" position="float"><label>Table 1</label><caption><p>Demographic and clinical characteristics of the DLB and PDD groups</p></caption><table frame="hsides" rules="groups"><thead><tr valign="top"><th rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1">DLB (n = 24)</th><th align="left" rowspan="1" colspan="1">PDD (n = 27)</th><th align="left" rowspan="1" colspan="1">p value</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Age, years</td><td align="left" rowspan="1" colspan="1">68.9 (7.0)</td><td align="left" rowspan="1" colspan="1">69.2 (8.8)</td><td align="left" rowspan="1" colspan="1">0.905</td></tr><tr><td align="left" rowspan="1" colspan="1">Sex, female/male</td><td align="left" rowspan="1" colspan="1">8/16</td><td align="left" rowspan="1" colspan="1">5/22</td><td align="left" rowspan="1" colspan="1">0.374</td></tr><tr><td align="left" rowspan="1" colspan="1">Education, years</td><td align="left" rowspan="1" colspan="1">14.2 (3.7)</td><td align="left" rowspan="1" colspan="1">13.6 (3.3)</td><td align="left" rowspan="1" colspan="1">0.536</td></tr><tr><td align="left" rowspan="1" colspan="1">Disease duration, years</td><td align="left" rowspan="1" colspan="1">2.4 (1.5)</td><td align="left" rowspan="1" colspan="1">12.4 (4.3)</td><td align="left" rowspan="1" colspan="1">0.000</td></tr><tr><td align="left" rowspan="1" colspan="1">Hallucination, n (%)</td><td align="left" rowspan="1" colspan="1">10 (41.7)</td><td align="left" rowspan="1" colspan="1">6 (22.2)</td><td align="left" rowspan="1" colspan="1">0.232</td></tr><tr><td align="left" rowspan="1" colspan="1">Delusions, n (%)</td><td align="left" rowspan="1" colspan="1">3 (12.5)</td><td align="left" rowspan="1" colspan="1">3 (11.1)</td><td align="left" rowspan="1" colspan="1">0.779</td></tr><tr><td align="left" rowspan="1" colspan="1">GDS</td><td align="left" rowspan="1" colspan="1">5.8 (4.1)</td><td align="left" rowspan="1" colspan="1">7.6 (3.5)</td><td align="left" rowspan="1" colspan="1">0.081</td></tr><tr><td align="left" rowspan="1" colspan="1">MMSE</td><td align="left" rowspan="1" colspan="1">25.7 (1.5)</td><td align="left" rowspan="1" colspan="1">26.2 (1.3)</td><td align="left" rowspan="1" colspan="1">0.228</td></tr><tr><td align="left" rowspan="1" colspan="1">MMP</td><td align="left" rowspan="1" colspan="1">22.5 (2.5)</td><td align="left" rowspan="1" colspan="1">22.3 (1.8)</td><td align="left" rowspan="1" colspan="1">0.681</td></tr><tr><td align="left" rowspan="1" colspan="1">L-dopa medications, n (%)</td><td align="left" rowspan="1" colspan="1">18 (75)</td><td align="left" rowspan="1" colspan="1">27 (100)</td><td align="left" rowspan="1" colspan="1">0.02</td></tr><tr><td align="left" rowspan="1" colspan="1">Dopamine agonist, n (%)</td><td align="left" rowspan="1" colspan="1">4 (17)</td><td align="left" rowspan="1" colspan="1">10 (37)</td><td align="left" rowspan="1" colspan="1">0.200</td></tr><tr><td align="left" rowspan="1" colspan="1">Cholinesterase inhibitors</td><td align="left" rowspan="1" colspan="1">3 (12.5)</td><td align="left" rowspan="1" colspan="1">0 (0)</td><td align="left" rowspan="1" colspan="1">0.195</td></tr><tr><td align="left" rowspan="1" colspan="1">Anxiolytic/antidepressive drugs</td><td align="left" rowspan="1" colspan="1">3 (12.5)</td><td align="left" rowspan="1" colspan="1">4 (14.8)</td><td align="left" rowspan="1" colspan="1">0.866</td></tr><tr><td align="left" rowspan="1" colspan="1">Antipsychotic drugs</td><td align="left" rowspan="1" colspan="1">2 (8)</td><td align="left" rowspan="1" colspan="1">0 (0)</td><td align="left" rowspan="1" colspan="1">0.446</td></tr><tr><td align="left" rowspan="1" colspan="1">UPRDS III (motor) total</td><td align="left" rowspan="1" colspan="1">29.6 (12.9)</td><td align="left" rowspan="1" colspan="1">42. 3(8.8)</td><td align="left" rowspan="1" colspan="1">0.000</td></tr><tr><td align="left" rowspan="1" colspan="1">Hoehn and Yahr stage</td><td align="left" rowspan="1" colspan="1">2.52 (0.6)</td><td align="left" rowspan="1" colspan="1">3.3 (0.5)</td><td align="left" rowspan="1" colspan="1">0.000</td></tr><tr><td align="left" rowspan="1" colspan="1">Motor subtype, PIGD/TD</td><td align="left" rowspan="1" colspan="1">16/5</td><td align="left" rowspan="1" colspan="1">16/7</td><td align="left" rowspan="1" colspan="1">0.877</td></tr><tr><td align="left" rowspan="1" colspan="1">Tremor at rest (mean score)</td><td align="left" rowspan="1" colspan="1">0.75 (1.0)</td><td align="left" rowspan="1" colspan="1">1.6 (1.3)</td><td align="left" rowspan="1" colspan="1">0.012</td></tr><tr><td align="left" rowspan="1" colspan="1">Postural tremor (mean score)</td><td align="left" rowspan="1" colspan="1">0.64 (0.7)</td><td align="left" rowspan="1" colspan="1">0.78 (0.9)</td><td align="left" rowspan="1" colspan="1">0.539</td></tr><tr><td align="left" rowspan="1" colspan="1">Intentional tremor (mean score)</td><td align="left" rowspan="1" colspan="1">0.39 (0.5)</td><td align="left" rowspan="1" colspan="1">0.3 (0.5)</td><td align="left" rowspan="1" colspan="1">0.525</td></tr><tr><td align="left" rowspan="1" colspan="1">Rigidity</td><td align="left" rowspan="1" colspan="1">2.6 (0.7)</td><td align="left" rowspan="1" colspan="1">3.1 (0.6)</td><td align="left" rowspan="1" colspan="1">0.053</td></tr><tr><td align="left" rowspan="1" colspan="1">Hand and feet bradykinesia</td><td align="left" rowspan="1" colspan="1">2.0 (0.8)</td><td align="left" rowspan="1" colspan="1">2.7 (0.6)</td><td align="left" rowspan="1" colspan="1">0.001</td></tr><tr><td align="left" rowspan="1" colspan="1">Postural stability</td><td align="left" rowspan="1" colspan="1">1.4 (0.8)</td><td align="left" rowspan="1" colspan="1">1.9 (0.7)</td><td align="left" rowspan="1" colspan="1">0.100</td></tr><tr><td align="left" rowspan="1" colspan="1">UPDRS IV: motor fluctuations</td><td align="left" rowspan="1" colspan="1">0.5 (1.6)</td><td align="left" rowspan="1" colspan="1">2.8 (1.9)</td><td align="left" rowspan="1" colspan="1">0.000</td></tr><tr><td align="left" rowspan="1" colspan="1">Dyskinesia</td><td align="left" rowspan="1" colspan="1">0.0 (0.0)</td><td align="left" rowspan="1" colspan="1">0.7 (1.2)</td><td align="left" rowspan="1" colspan="1">0.006</td></tr></tbody></table><table-wrap-foot><fn><p>Values are presented as mean (SD) unless otherwise indicated. GDS = Geriatric Depression Scale; PIGD = postural instability and gait difficulty subtype; TD = tremor dominant subtype.</p></fn></table-wrap-foot></table-wrap><table-wrap id="T2" orientation="portrait" position="float"><label>Table 2</label><caption><p>Neuropsychological performance of both groups</p></caption><table frame="hsides" rules="groups"><thead><tr valign="top"><td rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1">DLB</td><td align="left" rowspan="1" colspan="1">PDD</td><td align="left" rowspan="1" colspan="1">p value</td></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Memory (FCSRT)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Immediate recall</td><td align="left" rowspan="1" colspan="1">12.0 (3.0)</td><td align="left" rowspan="1" colspan="1">12.2 (2.9)</td><td align="left" rowspan="1" colspan="1">0.859</td></tr><tr><td align="left" rowspan="1" colspan="1"> Free recall</td><td align="left" rowspan="1" colspan="1">17.1 (6.6)</td><td align="left" rowspan="1" colspan="1">14.7 (5.8)</td><td align="left" rowspan="1" colspan="1">0.170</td></tr><tr><td align="left" rowspan="1" colspan="1"> Total recall</td><td align="left" rowspan="1" colspan="1">39.3 (5.8)</td><td align="left" rowspan="1" colspan="1">37.5 (7.3)</td><td align="left" rowspan="1" colspan="1">0.357</td></tr><tr><td align="left" rowspan="1" colspan="1"> Recognition</td><td align="left" rowspan="1" colspan="1">15.7 (0.8)</td><td align="left" rowspan="1" colspan="1">15.4 (0.8)</td><td align="left" rowspan="1" colspan="1">0.242</td></tr><tr><td align="left" rowspan="1" colspan="1"> Free delayed recall</td><td align="left" rowspan="1" colspan="1">5.8 (3.0)</td><td align="left" rowspan="1" colspan="1">5.7 (3.0)</td><td align="left" rowspan="1" colspan="1">0.879</td></tr><tr><td align="left" rowspan="1" colspan="1"> Total delayed recall</td><td align="left" rowspan="1" colspan="1">13.8 (2.1)</td><td align="left" rowspan="1" colspan="1">13.5 (2.5)</td><td align="left" rowspan="1" colspan="1">0.626</td></tr><tr><td align="left" rowspan="1" colspan="1">Language (BNT)</td><td align="left" rowspan="1" colspan="1">12.8 (1.8)</td><td align="left" rowspan="1" colspan="1">13.4 (1.3)</td><td align="left" rowspan="1" colspan="1">0.226</td></tr><tr><td align="left" rowspan="1" colspan="1"> Semantic fluency (animals), n</td><td align="left" rowspan="1" colspan="1">12.7 (3.7)</td><td align="left" rowspan="1" colspan="1">14.3 (3.3)</td><td align="left" rowspan="1" colspan="1">0.109</td></tr><tr><td align="left" rowspan="1" colspan="1"> Phonemic fluency (letter M), n</td><td align="left" rowspan="1" colspan="1">6.5 (3.4)</td><td align="left" rowspan="1" colspan="1">6.2 (2.5)</td><td align="left" rowspan="1" colspan="1">0.636</td></tr><tr><td align="left" rowspan="1" colspan="1">Attention/executive function</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Digit span forward</td><td align="left" rowspan="1" colspan="1">5.1 (1.1)</td><td align="left" rowspan="1" colspan="1">5.2 (0.7)</td><td align="left" rowspan="1" colspan="1">0.815</td></tr><tr><td align="left" rowspan="1" colspan="1"> Digit span backward</td><td align="left" rowspan="1" colspan="1">2.8 (1.1)</td><td align="left" rowspan="1" colspan="1">3.4 (0.8)</td><td align="left" rowspan="1" colspan="1">0.023</td></tr><tr><td align="left" rowspan="1" colspan="1"> TMT-A (correct lines)</td><td align="left" rowspan="1" colspan="1">22.3 (4.5)</td><td align="left" rowspan="1" colspan="1">23.8 (0.6)</td><td align="left" rowspan="1" colspan="1">0.122</td></tr><tr><td align="left" rowspan="1" colspan="1"> TMT-B (correct lines)</td><td align="left" rowspan="1" colspan="1">11.1 (10.3)</td><td align="left" rowspan="1" colspan="1">12.4 (8.9)</td><td align="left" rowspan="1" colspan="1">0.629</td></tr><tr><td align="left" rowspan="1" colspan="1"> MCST (categories)</td><td align="left" rowspan="1" colspan="1">2.2 (1.6)</td><td align="left" rowspan="1" colspan="1">3.0 (1.7)</td><td align="left" rowspan="1" colspan="1">0.093</td></tr><tr><td align="left" rowspan="1" colspan="1"> Perseverative errors (P%)</td><td align="left" rowspan="1" colspan="1">63.0 (20.2)</td><td align="left" rowspan="1" colspan="1">38.1 (21.7)</td><td align="left" rowspan="1" colspan="1">0.000</td></tr><tr><td align="left" rowspan="1" colspan="1"> Stroop Test part 3</td><td align="left" rowspan="1" colspan="1">15.1 (10.4)</td><td align="left" rowspan="1" colspan="1">20.3 (9.2)</td><td align="left" rowspan="1" colspan="1">0.066</td></tr><tr><td align="left" rowspan="1" colspan="1">Visuospatial and constructive abilities</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"> Copy designs</td><td align="left" rowspan="1" colspan="1">6.8 (2.2)</td><td align="left" rowspan="1" colspan="1">8.7 (2.2)</td><td align="left" rowspan="1" colspan="1">0.001</td></tr><tr><td align="left" rowspan="1" colspan="1"> Pentagon</td><td align="left" rowspan="1" colspan="1">3.7 (1.4)</td><td align="left" rowspan="1" colspan="1">5.2 (0.6)</td><td align="left" rowspan="1" colspan="1">0.000</td></tr><tr><td align="left" rowspan="1" colspan="1"> Clock Drawing Test</td><td align="left" rowspan="1" colspan="1">5.9 (2.2)</td><td align="left" rowspan="1" colspan="1">6.7 (2.2)</td><td align="left" rowspan="1" colspan="1">0.227</td></tr></tbody></table><table-wrap-foot><fn><p>FCSRT = Free and Cued Selective Reminding Test; BNT = Boston Naming Test; TMT = Trail Making Test.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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