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Neuropsihloški korelati mikrostrukturnih promena mozga utvrđenih metodom magnetne rezonance kod obolelih od blagog kognitivnog poremećaja i Alchajmerove bolesti / Neuropsychological correlates of microstructural brain damage visualized by magnetic resonance imaging in patients with mild cognitive impairment and Alzheimer's disease

<p>Alchajmerova bolest je najče&scaron;ća demencija od svih demencija i karakteri&scaron;e je depozicija senilinih plakova i neurofibrilarnih klubadi u kortikalnim moždanim regionima, koje daljim razvojem bolesti postaju atrofične. Klinički se karakteri&scaron;e smetnjma na planu pamćenja, egzekutivnih funkcija, pažnje i ostalih kognitivnih funkcija uz odustsvo sposobnosti samostalnog funkcionisanja u svakodnevnom životu. Blagi kognitivni poremeća (BKP) je klinički entitet koji se smatra početnim stadijumom demencije u kom se registruju smetnje na planu pamćenja, ali i drugih kognitvnih funkcija, uz očuvanu funkcionalnost u svakodnevnom životu. Kod obe bolesti je utvrđeno da pored kortikalnog zahvatanja, patolo&scaron;kim procesom je zahvaćena i bela masa mozga. U dana&scaron;nje vreme se mirkostrukturno o&scaron;tećenje bele mase mozga može ispitati difuzionim tenzorskim imidžinogom (DTI) na magnentoj rezonanci mozga (MR). Cilj: Utvrditi razlike neuropsiholo&scaron;kih skorova i razlike DTI parametara između obolelih od AB, BKP i kontrolne grupe zdravih ispitanika, kao i utvrditi da li postoji korelacija između neuropsiholo&scaron;kih skorova i DTI parametara kod BKP i AB.&nbsp; Metode: U istraživanje je uključeno tri ispitivane grupe od po 30 ispitanika: oboleli od AB u blagom stadijumu bolesti, oboleli od amnestičkog multi-domen BKP i kontrolna grupa zdravih ispitanika. Dijagnoza kod obolelih u obe grupe je postavljena na osnovu kliničkih kriterijuma aktuelnih dijagnostičkih kriterijuma iz 2011. godine. Kod svih ispitanika je sprovedeno detaljno neuropsiholo&scaron;ko testiranje u cilju procene kognitivnih funkcija (smetnji na planu pamćenja, egzekutivnih funkcija, pažnje, govora, vizuospacijalnih i vizuokonstrukcionih sposobnosti), depresivnosti i drugih neuropsihijatrijskih simptoma i kvaliteta života. Samo je kod obolelih od AB dopunski vr&scaron;ena procena sposobnosti svakodnevnog funkcionisanja. Kognitivne funkcije su ispitane formiranjem kognitivnih domena, na osnovu pretpostavke o zajedničkom predmetu merenja kori&scaron;ćenih testova. Potom je načinjen MR mozga, u okviru koje je analiziran i DTI. Dalja obrada DTI je sprovedena primenom TBSS metode, čime su dobijene vrednosti DTI parametara: frakcione anizotropije (FA), srednje difuzivnosti (SD), radijalne difuzivnosti (RD) i aksijalne difuzivnosti (DA). Nakon toga je načinjena korelacija neuropsiholo&scaron;kog postignuća i DTI parametara kori&scaron;ćenjem Pirsonovog, odnosno Spirmanovog koeficijenta korelacije. Rezultati: Oboleli od AB su imali lo&scaron;ije postignuće na planu vizuelnog pamćenja, verbalnog pamćenja, neposrednog upamćivanja, odloženog prisećanja, pažnje, govora, egzekutivnih funkcija, mi&scaron;ljenja, radne memorije i vizuospacijalnih i vizuokonstrukcionih sposobnosti u odnosu na kontrolnu grupu zdravih. Oboleli od BKP su imali lo&scaron;ije postignuće u odnosu na kontrolnu grupu zdravih u domenima vizuelno pamćenje, neposredno upamćivanje, odloženo prisećanje, govor, mi&scaron;ljenje i vizuospacijalne i vizuokonstrukcione sposobnosti. Obe grupe obolelih su ispoljile vi&scaron;e depresivnih simptoma u odnosu na kontrolnu grupu zdravih ispitanika. Takođe, obe grupe obolelih ispoljavaju statistički značajno vi&scaron;e neuropsihijatrijskih simptoma u odnosu na zdrave ispitanike, gde se kod obolelih od AB registruju sumanute ideje, halucinacije, agitacija, euforija, dezinhibicija, ritabilnost i apatija, dok se kod obolelih od BKP registruju anksioznost i iritabilnost. Oboleli od AB imaju lo&scaron;iji kvalitet života u odnosu na zdrave ispitanike, dok između oboleli od BKP i zdravih ispitanika nema razlike u proceni kvaliteta života. &Scaron;to se tiče DTI parametara, oboleli od AB imaju niži FA i vi&scaron;u SD, RD i DA u odnosu na zdrave ispitanike na vi&scaron;e puteva bele mase: prednji krak kapsule interne, prednja korona radijata, telo korpusa kalozuma, cingulum, kapsula eksterna, fornix-strija terminalis, koleno korpusa kalozuma, donji fronto-okcipitalni fascikulus, zadnja korona radijata, gornji fronto-okcipitalni fascikulus, gornji longitudinalni fascikulus i fascikulus uncinatus. Oboleli od BKP imaju sniženu FA i povi&scaron;enu SD, RD i DA u regiji forniksa u odnosu na zdrave ispitanike. Kod obolelih od AB registrovane su značajne povezanosti mikrostrukturnog o&scaron;tećenja bele mase i o&scaron;tećenja svih kognitivnih domena, izuzev domena mi&scaron;ljenje, dok su kod obolelih od BKP registrovane značajne povezanosti mikrostrukturnog o&scaron;tećenja bele mase i o&scaron;tećenja svih kognitivnih domena, izuzev domena egzekutivne funkcije. U grupi obolelih od BKP je bilo vi&scaron;e registrovanih korelacija o&scaron;tećenja domena verbalno pamćenje, odloženo prisećanje i govor sa o&scaron;tećenjem bele mase mozga, dok je kod AB bilo vi&scaron;e registrovanih korelacija o&scaron;tećenja domena vizuelno pamćenje, neposredno upamćivanje, pažnja, radna memorija i vizuospacijalne i vizuokontrukcione sposobnosti sa o&scaron;tećenjem bele mase mozga. Depresivnost je jedino u grupi BKP značajno korelirala sa o&scaron;tećenjem određenih puteva bele mase mozga. Zaključak: U blagom stadijumu obolelih od AB se registruje kognitivno o&scaron;tećenje svih ispitivanih domena, vi&scaron;e su ispoljeni depresivni simptomi, utvrđen je veliki broj neuropsihijatrijskih simptoma i naru&scaron;en je kvalitet života u odnosu na zdrave ispitanike. Kod obolelih od BKP je registrovano kognitivno o&scaron;tećenje vi&scaron;e od pola procenjivanih kognitivnih funkcija, vi&scaron;e su ispoljeni depresivni simptomi i utvrđeno prisustvo anksioznosti i iritabilnosti, dok kvalitet života nije naru&scaron;en u ovoj fazi bolesti u odnosu na zdrave ispitanike. Rezultati vezani za mikrostrukturno o&scaron;tećenja mozga u najranijim fazama AB ukazuju da je neuronska mreža značajno o&scaron;tećena u najranijim kliničkim fazama bolesti, dok je u stadijumu BKP izolovana na o&scaron;tećenje u regiji forniksa. U grupi obolelih od BKP je bilo vi&scaron;e registrovanih korelacija o&scaron;tećenja domena verbalno pamćenje, odloženo prisećanje i govor sa o&scaron;tećenjem bele mase mozga, dok je kod AB bilo vi&scaron;e registrovanih korelacija o&scaron;tećenja domena vizuelno pamćenje, neposredno upamćivanje, pažnja, radna memorija i vizuospacijalne i vizuokontrukcione sposobnosti sa o&scaron;tećenjem bele mase mozga. Stepen depresivnosti i o&scaron;tećenje bele mase mozga je povezano isključivo na nivou BKP.</p> / <p>Alzheimer&#39;s disease (AD) is the most common dementia of all dementia with deposition of senile plaques and neurofibrillary tangles in cortical brain regions, which become atrophic in the further disease development. It`s main clinical characteristics are impairment of memory, executive function, attention and other cognitive functions with impairment in daily living activities. Mild cognitive impairment (MCI) is a clinical entity considered as an initial stage of dementia with present memory impairment, as well as other cognitive functions, while maintaining the functionality of the everyday life. In both diseases, pathological processes affect also the white matter of the brain. Nowadays, microstructural damage of the brain white matter is diagnosed by using diffusion tensor imaging (DTI) in the brain magnetic resonance imaging (MR). Objective: The aim of this study was to determine differences in neuropsychological scores and differences in DTI parameters between patients with AD, MCI and control groups of healthy subjects, as well as to determine whether there is a correlation between scores and DTI parameters in MCI and AD.&nbsp; Methods: The study included three groups of 30 patients each: of AD patients in the mild stage of the disease, patients with multi-domain amnestic MCI, and healthy controls. The patient&rsquo;s diagnosis are based upon clinical criteria of current diagnostic criteria proposed in 2011. All patients had assessment of cognitive functions (impairment of memory, executive function, attention, language, visuospatial and construction abilities), depressive symptoms and other behavioral disorders and quality of life. Only in patients with AD, we also assessed ability of daily living activities. Cognitive functions were tested by forming cognitive domains, based on the assumption of a common object of measurement of analyzed tests. Further, participants had MRI scan, in which DTI was analyzed. DTI post-processing was carried out by using TBSS method, whereby the values of DTI parameters were: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (DA). We conducted correlation analysis of the neuropsychological achievements and DTI parameters using Pearson or Spearman&rsquo;s correlation coefficient, dependent on variable distribution. Results: The patients with AD had lower scores in the field of visual memory, verbal memory, immediate and delayed recall, attention, language, executive functions, reasoning, working memory and visuospatial and construction abilities compared to the control group. Patients with MCI had lower scores compared to the control group in the domains of visual memory, immediate and delayed recall, language, reasoning, and visuospatial and construction abilities. Both groups of patients have more depressive symptoms in relation to the control group of healthy subjects. In addition, both groups of patients exhibited a significantly higher degree of behavioral disorders as compared to healthy subjects, where AD patients experienced delusions, hallucinations, agitation, euphoria, disinhibition, irritability and apathy, while MCI patients experienced anxiety and irritability. Patients with AD had a poor quality of life compared to healthy subjects, whereas people with MCI did not. As for the parameters of DTI, AD patients had decrease of FA and increase of MD, RD, and DA compared to the healthy subjects in the multiple white matter tracts: anterior limb of internal capsule, anterior part of corona radiata, the body of the corpus callosum, cingulum, external capsule, fornix- striae terminalis, genu of the corpus callosum, inferior frontal-occipital fasciculus, posterior corona radiata, superior frontal-occipital fasciculus, superior longitudinal fasciculus and fasciculus uncinatus. Patients with MCI had decreased FA and increased MD, RD and DA in the fornix compared to healthy subjects. In AD patients, there was significant association between microstructural white matter brain damage and all cognitive domains, except domain reasoning, while in patients with MCI significant association was evident between microstructural white matter damage and all cognitive domains, except the domain of executive function. Results related to the microstructural white matter brain damage in mild AD indicates that wide neural network is significantly damaged at the earliest clinical stages of the disease, while in MCI stage only fornix shows microstructural white matter brain damage. Level of impairment of verbal memory, delayed recall and language correlates more frequently in MCI group compared to mild AD group, where impairment in the field of visual memory, immediate recall, attention, working memory and visuospatial and construction abilities correlates more frequently with white matter brain damage. Association of depressive symptoms and white matter brain damage was significant in MCI patients. Conclusion: In mild AD, cognitive impairment is present in all cognitive domains; patients experience more depressive symptoms and wider spectrum of behavioral disorders with compromised quality of life compared to healthy subjects. In MCI patients, cognitive impairment is present in more than half of the assessed cognitive functions; patients also experience more depressive symptoms, as well as anxiety and irritability without quality of life deterioration compared to healthy subjects. Results related to the microstructural white matter brain damage in mild AD indicates that wide neural network is significantly damaged at the earliest clinical stages of the disease, while in MCI stage only fornix shows microstructural white matter brain damage. Level of impairment of verbal memory, delayed recall and language correlates more frequently in MCI group compared to mild AD group, where impairment in the field of visual memory, immediate recall, attention, working memory and visuospatial and construction abilities correlates more frequently with white matter brain damage. The degree of depression correlated significantly with white matter brain damage solely at the level of MCI.</p>

Identiferoai:union.ndltd.org:uns.ac.rs/oai:CRISUNS:(BISIS)111008
Date24 October 2019
CreatorsVujanić Stankov Tijana
ContributorsSemnic Marija, Kozić Duško, Simić Svetlana, Bugarski-Ignjatović Vojislava, Boban Jasmina, Daković Marko, Petrušić Igor
PublisherUniverzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, University of Novi Sad, Faculty of Medicine at Novi Sad
Source SetsUniversity of Novi Sad
LanguageSerbian
Detected LanguageUnknown
TypePhD thesis

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