Bakgrund: Diabetes typ 2 innebär ökad risk för kognitiv sjukdom. Forskning visar att båda sjukdomarna kommer öka markant de kommande 20 åren, framför allt på grund av en allt äldre befolkning men också av den kraftig ökningen av livsstilssjukdomar som fetma och insulinresistens. Distriktssköterskor har en viktig roll när det kommer till att begränsa den utvecklingen. Genom det hälsofrämjande och sjukdomsförebyggande arbetet kan distriktssköterskan synliggöra hälsoproblem, ta hänsyn till patientens unika livssituation med copingstrategier och därefter tillsammans med patienten utarbeta en plan för förändringsarbete mot en mer hälsosam livsstil. Samarbetet och det delade ansvaret stärker patientens position och självkänsla. Under förändringsarbetet kan sjuksköterskan finnas för att ge stöd och råd för att personen ska komma vidare i adaptionsprocessen. En framgångsrik modell som kan användas för ett personcentrerat sjukdomsförebyggande arbete är Riktade hälsosamtal. Syfte: Syftet med studien var att undersöka förekomsten av diabetes typ 2 och/eller kognitiv dysfunktion hos personer över 60 år i SNAC-B-studien, om det finns ett samband mellan sjukdomarna samt vilka riskfaktorer som har stor betydelse för att förebygga sjukdomarna. Metod: Studien var en deskriptiv tvärsnittsstudie med kvantitativ ansats som utgått från data ur SNAC-B (The Swedish National study on Aging and Care) i Blekinge. Resultat: Studien visade inget statistiskt samband mellan diabetes typ 2 och kognitiv dysfunktion men det finns ett antal riskfaktorer som har stor betydelse för respektive sjukdom och flera av dessa är kopplade till levnadsvanor. Slutsats: Ohälsosamma levnadsvanor ökar risken för diabetes typ 2 och kognitiv dysfunktion. Högt långtidsblodsocker, visceralt fett och övervikt ökar risken mest för diabetes typ 2. Utöver ålder och utbildningsnivå var det alkoholvanor, fysisk aktivitet och högt långtidsblodsocker som mest ökar risken för kognitiv dysfunktion. / Background: Type-2 diabetes implies an increased risk of cognitive disease. Research shows that both diseases will increase significantly over the next 20 years, primarily due to an increasingly elderly population, but also due to the considerable increase in lifestyle diseases such as obesity and insulin resistance. District nurses play an important role when it comes to limiting that development. By health promotion and disease prevention efforts, the district nurse can make health problems visible, take into account the patient's unique life situation with coping strategies and then, in cooperation with the patient, frame a plan for change towards a healthier lifestyle. The cooperation and the shared responsibility strengthen the patient's position and self-esteem. During the work for change, the nurse is able to be there to provide support and advice for the person to progress in the adaptation process. A successful model that can be used for person-centred disease prevention work is ‘Individual health dialogue’. Aim: The aim of the study was to investigate the occurrence of type-2 diabetes and/or cognitive dysfunction in people over 60 years of age in the SNAC-B study, whether there is a connection between the diseases and which risk factors are of great importance in preventing the diseases. Method: The study was a descriptive cross-sectional study with a quantitative approach, based on data from SNAC-B (The Swedish National study on Aging and Care) in Blekinge. Results: The study showed no statistical relationship between diabetes type-2 and cognitive dysfunction, but it showed a number of risk factors that are of great importance for the respective disease, and several of these are connected to lifestyle habits. Conclusion: Unhealthy lifestyles increase the risk of type-2 diabetes and cognitive dysfunction. High long-term blood sugar, visceral fat and obesity increase the risk of developing type-2 diabetes. In addition to age and education level, alcohol habits, physical activity and high long-term blood sugar increase the risk of cognitive dysfunction.

Abstrakt Bakgrund: Forskning visar att generell anestesi kan bidra till kognitiv dysfunktion postoperativt. En alltför djup anestesi och/eller en lång duration av anestesi är två faktorer som kan inverka på kognitionen med besvär såsom minnesproblem och koncentrationssvårigheter. Anestesisjuksköterskans roll är att individanpassa anestesin för att inte orsaka för djup anestesi och därmed har det blivit alltmer vanligt att monitorera anestesidjupet för att minska på onödigt lidande för patienten. Syfte: Syftet är att kartlägga anestesidjup och anestesiduration  hos patienter med självskattad  kognitiv svikt efter elektiv ortopedisk operation. Metod: För att kartlägga detta valdes en retrospektiv observationsstudie med tvärsnittsdesign med insamlad data från kvalitetsregister. Resultat: Av 920 patienter var det 116 patienter som uppgav kognitiv dysfunktion dag 1 postoperativt och upp till över 16 dagar postoperativt med  ett genomsnittsvärde på 37,7 i entropy och 104,4 minuter i anestesiduration. Slutsats: Desto längre duration av anestesin och ju djupare anestesi desto mer kognitiv påverkan postoperativt. Anestesidjupsmonitorering bör användas mer frekvent och önskvärt är att bedöma kognition preoperativt med ett mätinstrument för att kunna se om skillnad finns postoperativt.

Submitted by Ubirajara Cruz (ubirajara.cruz@gmail.com) on 2017-06-29T14:55:18Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Fernanda_Krug.pdf: 1138754 bytes, checksum: 331c1dbcf37a0662cc3b67ccb9eb9872 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2017-06-29T16:37:31Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Fernanda_Krug.pdf: 1138754 bytes, checksum: 331c1dbcf37a0662cc3b67ccb9eb9872 (MD5) / Made available in DSpace on 2017-06-29T16:37:31Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Fernanda_Krug.pdf: 1138754 bytes, checksum: 331c1dbcf37a0662cc3b67ccb9eb9872 (MD5) Previous issue date: 2016-03-18 / Sem bolsa / Com o aumento da expectativa de vida dos cães, enfermidades vinculadas a senilidade tem sido estudada, tais como a síndrome de disfunção cognitiva (SDCC). Devido a importância de conscientização dessa síndrome objetivamos avaliar a os tipos de distúrbios cognitivos em cães adultos/maduros através de questionário observacional e de testes de reatividade. Primeiramente, realizamos uma revisão bibliográfica abordando fisiopatogenia, métodos de avaliação, testes laboratoriais e formas de tratamento. Em seguida, elaboramos um questionário sobre comportamento com 28 perguntas, disponibilizado em rede social e respondido por tutores de cães acima de sete anos de idade. As questões foram dividas nas categorias de desorientação, interação socioambiental, ciclo sono-vigília, casa sujidade e atividade. Cada uma foi avaliada com escores numéricos, e com a soma da pontuação determinou-se que: o cão com disfunção cognitiva canina (DCC) acima de 50 pontos, o cão Borderline (BL) entre 40 a 49 pontos e sem alterações comportamentais (SAC) até 39 pontos. Também se avaliou há interferência na relação tutor/cão em caso de alteração comportamental. Além, do questionário foi realizado o teste de reatividade (open field, curiosidade, interação com humano e do espelho) com dez cães que apresentavam queixa comportamental, os quais seus tutores responderam ao questionário. Para a análise dos dados utilizou-se os testes ANOVA, as médias foram testadas com Tukey e qui-quadrado. Com relação ao questionário verificou-se nos 112 questionários respondidos, que 25,8% (29) dos cães apresentavam DCC, 41,9% (47) eram BL e 32,1% (36) eram SAC. Nas avaliações das categorias foi constatado que o grupo DCC obteve sempre as maiores médias do somatório, diferindo (p ≤ 0,005) do SAC e BL nas categorias a atividade e ciclo sono–vigília. Todos os tutores relataram no questionário que as alterações comportamentais não interferem na rotina do tutor com o seu cão. Entre os dez cães que participaram do teste de reatividade, constatou-se que dois cães tinham DCC, três eram BL, cinco eram SAC através da análise do questionário. Os cães com DCC tiveram alterações em todos testes de reatividade, exceto no de curiosidade. No open field esses animais urinaram durante o teste diferindo dos demais (p ≤ 0,05). No exame de interação com humanos e no do espelho os cães com DCC não realizaram a interação (p≤0,005) nem com a pessoa ou com o objeto, enquanto os demais grupos apresentaram a interação. Com os estudos realizados conclui-se que cães com DCC tem déficit cognitivo nas atividades, ciclo sono vigília, e interação social. / With increasing life expectancy of dog’s diseases related senility, has been studied, such as cognitive dysfunction syndrome (SDCC). Due to the importance of awareness of this syndrome, we aimed to evaluate the types of cognitive disorders in adult / mature dogs through observational questionnaire and reactivity tests. First, we conducted a literature review addressing pathophysiology, evaluation methods, laboratory tests and forms of treatment. Then, we developed a behavior on questionnaire with 28 questions, available on social network and answered by up dog guardians seven years old. The questions were divided in disorientation categories, socio-environmental interaction, sleep-wake cycle, house soiling and activity. Each was evaluated with numerical scores, and the sum of scores was determined that: the dog with canine cognitive dysfunction (DCC) above 50, the dog Borderline (BL) from 40 to 49 points and without behavioral changes (SAC) to 39 points. Also evaluated for interference in the mentor / dog relationship in case of behavioral change. In addition, the survey was conducted the reactivity test (open field, curiosity, with human interaction and mirror) with ten dogs with behavioral complaint, which his tutors answered the questionnaire. For data analysis, we used the ANOVA tests, the averages were tested with Tukey and chi-square. Regarding the questionnaire there was the 112 responses, 25.8% (29) of the dogs had DCC, 41.9% (47) were BL and 32.1% (36) were SAC. In the evaluations of the categories it was found that the DCC group always had the highest average of the sum, differing (p ≤ 0.005) of the SAC and BL in the categories activity and sleep-wake cycle. All tutors reported in the questionnaire that behavioral changes do not interfere with the tutor of the routine with your dog. Among the ten dogs that participated in the reactivity test, it was found that two dogs had DCC, three were BL, and five were SAC by questionnaire analysis. Dogs with CHD had changes in all reactivity tests, except curiosity. In the open field the animals urinated during the test differed significantly (p ≤ 0.05). In the examination of interaction with humans and the mirror dogs with CHD did not perform the interaction (p≤0,005) or with the person or the object, while the other groups presented the interaction. With the studies, it was concluded that dogs with CHD have cognitive impairment in activities, sleep wake cycle, and social interaction.

Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in detail. I hypothesize that mossy cells are critical targets for ionizing radiation, whereby damage to these targets contributes to the mechanisms associated with radiation-induced hippocampal dysfunction. To test this idea, wild-type mice were exposed to clinically relevant doses of cranial x-ray irradiation and their hippocampi were examined 1 month and 3 months post treatment. A significant decline in both the number of mossy cells and their activity were observed. In addition, dentate granular cells demonstrated reduced levels of activity, as well as reduced proliferation within the subgranular zone. A second cohort of mice was introduced to a novel environment in order to induce the expression of immediate early genes. Analysis of c-Fos mRNA yielded a significant increase in control but not irradiated animals, suggesting that radiotherapy impaired immediate early gene expression and resultant functional behavioral outcomes. These findings support the proposition that radiation-induced damage to mossy cells contributes to hippocampal deficiencies which result in cognitive dysfunction.

ΜΕΛΕΤΗ Α΄ Στόχος: Να διερευνηθεί αν ο κινητικός υπότυπος της αστάθειας κορμού και δυσχέρειας της βάδισης (ΑΚΔΒ) σχετίζεται με τη γνωστική δυσλειτουργία που εμφανίζουν οι ασθενείς με νόσο του Parkinson (NP) χωρίς άνοια. Μέθοδοι: Χορηγήσαμε μια συστοιχία επιλεγμένων νευροψυχολογικών δοκιμασιών σε δύο ομάδες μη ανοϊκών ασθενών με ήπια έως μέτριας βαρύτητας νόσο κατηγοριοποιημένους είτε στον υπότυπο της ΑΚΔΒ είτε σε υπότυπο μη ΑΚΔΒ, καθώς και σε μια ομάδα υγιών μαρτύρων. Οι ομάδες εξισώθηκαν κατά το δυνατόν όσον αφορά δυνητικούς συγχυτικούς παράγοντες που επηρεάζουν τις νευροψυχολογικές επιδόσεις. Αποτελέσματα: Δε διαπιστώθηκαν σημαντικές διαφορές μεταξύ των δύο ομάδων ασθενών στην επίδοση σε οποιαδήποτε από τις χορηγηθείσες νευροψυχολογικές δοκιμασίες. Παρόλα αυτά, σε σχέση με τους μάρτυρες υπήρξε μια τάση διαφοροποίησης ως προς το κυρίαρχο πρότυπο της γνωστικής δυσλειτουργίας. Η ομάδα με τον υπότυπο της ΑΚΔΒ είχε βραδύτερες επιδόσεις σε μια δοκιμασία ψυχοκινητικής ταχύτητας και γνωστικής ευελιξίας, ενώ η ομάδα με υπότυπο της νόσου μη ΑΚΔΒ είχε χειρότερες επιδόσεις στις μετρήσεις της λεκτικής μάθησης και της οπτικοχωρικής αντίληψης. Συμπεράσματα: Ο υπότυπος της ΑΚΔΒ δε συσχετίσθηκε με σοβαρότερα γνωστικά ελλείμματα και έτσι είναι πιθανό οι μηχανισμοί της γνωστικής δυσλειτουργίας να είναι, έως ένα ορισμένο βαθμό, κοινοί ανεξάρτητα από τον κινητικό υπότυπο της νόσου. ΜΕΛΕΤΗ Β Στόχος: Να διερευνηθεί αν υπάρχει συσχέτιση μεταξύ της ΝΡ και του γονιδίου CHRNA4, το οποίο κωδικοποιεί την α4 υπομονάδα του α4β2 νικοτινικού υποδοχέα της ακετυλοχολίνης (nAChR). Mέθοδοι: Στη μελέτη συμμετείχαν 100 ασθενείς με ΝΡ και 105 μάρτυρες, εξισωμένοι ως προς την ηλικία και το φύλο και ανήκοντες στην ίδια πληθυσμιακή ομάδα με τους ασθενείς. Ο γενετικός δείκτης που εξετάσθηκε είναι ένας μονονουκλεοτιδικός πολυμορφισμός στο 5ο εξόνιο του γονιδίου CHRNA4 (dbSNP rs1044396). Έγινε απομόνωση DNA γονιδιώματος από περιφερικό αίμα και ακολούθησε ανάλυση μεγέθους περιοριστικών τμημάτων μετά από αλυσωτή αντίδραση πολυμεράσης και κατάτμηση των προϊόντων αυτής με το ένζυμο Hha I. Μια υποομάδα 42 ασθενών υποβλήθηκαν επίσης σε λεπτομερή κλινική και νευροψυχολογική εκτίμηση. Η στατιστική ανάλυση για τη σύγκριση της συχνότητας των αλληλομόρφων και των γονοτύπων μεταξύ των ομάδων έγινε με τη δοκιμασία χ2, και τον ακριβή έλεγχο Fisher εάν έστω ένα κελί είχε n<5. Υπολογίστηκαν οι σχετικοί κίνδυνοι και τα κατά 95% διαστήματα αξιοπιστίας τους που αντιστοιχούσαν στα αλληλόμορφα και τους γονότυπους. Χρησιμοποιήθηκε η λογιστική ανάλυση παλινδρόμησης εάν ήταν απαραίτητη η προσαρμογή για την ηλικία ή το φύλο. Αποτελέσματα: Οι συχνότητες των γονοτύπων στην ομάδα των ασθενών (TT 34%; CT 58%; CC 8%) σε σύγκριση με τις συχνότητες των γονοτύπων στην ομάδα των μαρτύρων (TT 28.6 %; CT 47.6%; CC 23.8 %) παρουσίασαν στατιστικά σημαντική διαφορά (χ2 = 9.48, df = 2, p = 0.009). Η ομοζυγωτία CC συσχετίσθηκε με χαμηλότερο κίνδυνο παρουσίας της ΝΡ (CC vs φορείς T: OR = 0.28; 95% CI = 0.12–0.65; p = 0.002; στατιστική ισχύς 93.1%). Παρατηρήθηκε επίσης απόκλιση στην κατανομή των αλληλομόρφων μεταξύ των ασθενών και των μαρτύρων. Υπήρχε σημαντικά χαμηλότερη συχνότητα του αλληλόμορφου C μεταξύ των ασθενών (37%) σε σχέση με τους μάρτυρες (47.6%) (χ2 = 4.73; df = 1; OR=0.65; 95% CI = 0.44–0.96; p = 0.03). Η ανάλυση διαστρωμάτωσης έδειξε ότι η διαφορά στην κατανομή των γονοτύπων μεταξύ ασθενών και μαρτύρων ήταν στατιστικά σημαντική και συγκριτικά μεγαλύτερη στο θήλυ φύλο σε σχέση με το άρρεν φύλο και στους ασθενείς με εκδήλωση ΝΡ σε όψιμη ηλικία ( > 50 ετών) σε σχέση με αυτούς που εμφάνισαν πρώιμης έναρξης νόσο (< 50 ετών). Οι ασθενείς με ΝP που ανιχνεύθηκαν να φέρουν το γονότυπο CC και υποβλήθηκαν σε νευροψυχολογική αξιολόγηση έτειναν να έχουν καλύτερα διατηρημένες τις γνωστικές λειτουργίες που σχετίζονται με την προσοχή και την ταχύτητα επεξεργασίας των πληροφοριών. Συμπεράσματα: Η παρουσία του αλληλομόρφου C (dbSNP rs1044396) του γονιδίου CHRNA4 συνδέεται με μειωμένο κίνδυνο ΝΡ κατά 35%. Επίσης, τα άτομα με το γονότυπο CC εμφανίζουν σχεδόν τρισήμισυ (3,5) φορές χαμηλότερο κίνδυνο νόσου του Parkinson. Η ποικιλομορφία του γονιδίου CHRNA4 φαίνεται ότι σχετίζεται ιδιαίτερα με την επιρρέπεια εκδήλωσης της ΝΡ με ηλικιακά όψιμη έναρξη της νόσου, και επίσης με τις γνωστικές λειτουργίες των ασθενών χωρίς άνοια, ειδικά αυτές που εξαρτώνται από την προσοχή και την οπτικοκινητική αντίληψη. / Study A Aim: To investigate whether there is an association of the postural instability and gait difficulty (PIGD) motor subtype with cognitive dysfunction in non-demented Parkinson’s disease (PD) patients. Methods: We administered a battery of selected neuropsychological tests to assess attention, psychomotor speed, executive functions (set shifting ability and inhibitory control), visuospatial perception and visual constructive ability to two groups of non-demented patients with mild to moderate disease classified either as PIGD or as non-PIGD subtype and to a group of healthy controls. Groups were matched on potential confounders of neuropsychological performance. Results: No significant differences were revealed between the two groups of patients in the performance of any of the administered neuropsychological tests. However, relative to controls there was a tendency towards a differential pattern of cognitive dysfunction. The PIGD group had slower performance in a test of psychomotor speed and cognitive flexibility, whilst the non-PIGD group performed worse in measures of verbal learning and visuo-spatial perception. Conclusions: The PIGD subtype was not associated with more severe cognitive deficits and may to a certain extent share common mechanisms of cognitive dysfunction with non-PIGD subtypes. Study B Aim: to investigate whether there is an association between PD and a variation in the CHRNA4 gene coding for the α4 subunit, the primary subunit of the α4β2 brain nicotinic acetylcholine receptors. Methods: Patients (N=100) and controls (N=105), matched on the basis of sex, age and ethnicity, were genotyped for a single nucleotide polymorphism at cDNA position 1860 lying within the 5th exon of the CHRNA4 gene. DNA was extracted from peripheral blood samples and genotyping was done by PCR-based restriction fragment length polymorphism analysis. A subset of 42 patients also received detailed clinical and cognitive assessments. Comparisons of allele and genotype frequencies between groups were performed using the χ2 test, and the Fisher exact test if one cell had n<5. The relative risk for genotypes and alleles was estimated through calculation of odds ratios (ORs) with 95% confidence intervals (CIs). Logistic regression analysis was used if adjustment for age or sex was necessary. Results: The genotype frequencies in the patients group (TT 34%; CT 58%; CC 8%) vs. the genotype frequencies in the control group (TT 28.6 %; CT 47.6%; CC 23.8 %) demonstrated a statistically significant difference (χ2 = 9.48, df = 2, p = 0.009). CC homozygosity was associated with a lower risk of PD (CC vs T carriers: OR = 0.28; 95% CI = 0.12–0.65; p = 0.002). Also, the allelic distribution was significantly different between patients and controls. There was a significantly lower frequency of the C allele among the patients with PD (37%) as compared with the controls (47.6%) (χ2 = 4.73; df = 1; OR=0.65; 95% CI = 0.44–0.96; p = 0.03). Stratified analysis showed that the difference in the genotypic distribution between cases and controls was significant among females but did not reach significance among males. The frequency of CC homozygotes was also significantly lower in the group of patients with late onset PD than in the controls, but it was not significantly different between the early onset group of patients and the controls. CC homozygotes also tended to have better performance than T carriers on measures of attention and psychomotor speed (Trail Making Test part A and Symbol Digit Modalities Test). Conclusions: The presence of the C allele at SNP rs1044396 of the CHRNA4 gene is associated with a decreased risk for PD by 35%. Moreover, the CC genotype lowers the risk for PD by ~ 3.5 fold. Variation in the CHRNA4 gene may particularly influence susceptibility for late onset PD and further be associated with measurable effects on overt cognitive performance of yet not-demented PD patients, specifically the part loading on attentional capacities.

Altersassoziiert entwickeln Hunde eine Erkrankung, die in vielen Aspekten der Alzheimer-Krankheit des Menschen ähnelt. Das canine kognitive Dysfunktionssyndrom äußert sich klinisch u.a. durch Desorientierung in vertrauter Umgebung, Vergessen von Kommandos und einen gestörten Schlaf-Wach-Rhythmus. Aus der Literatur ist bekannt, dass in den Gehirnen von alten Hunden regelmäßig Aβ- und selten Tauablagerungen zu beobachten sind. Allerdings erfolgte bisher kein Nachweis des hochgradig zytotoxischen und modifizierten pE3Aβ. Auch Veränderungen der mikroglialen Morphologie wurden bisher nicht beschrieben. Insgesamt lagen in dieser Studie 24 euthanasierte Rasse- und Mischlingshunde verschiedenen Alters vor. Fünf dieser Tiere besaßen ein durchschnittliches Alter von 2,1 Jahren und dienten als Kontrollgruppe. Die anderen 19 Hunde waren 8 bis 19 Jahre alt und wurden entsprechend ihrer Größe und des Gewichts in die drei Kategorien kleine (≤ 10 kg), mittelgroße (10 – 25 kg) und große Hunde (> 25 kg) unterteilt. Die Gehirne wurden aus den Schädeln präpariert und in 4 % Paraformaldehyd fixiert. Anschließend erfolgte die Präparation des frontalen und entorhinalen Kortex sowie der Hippokampusformation, die in 30%iger Saccharoselösung vitrifiziert und mittels Methylbutan bei -80 °C eingefroren wurden. Von den Regionen wurden Kryoschnitte mit einer Dicke von 40 µm angefertigt und diese anhand immunhistologischer Färbungen auf das Vorhandensein von Ablagerungen, bestehend aus den Amyloidsubtypen Aβ8-17 und pE3Aβ, sowie aus hyperphosphorylierten Tau, untersucht. Die Morphologie und das Aktivitätsstadium der Mikroglia wurden mit Antikörpern gegen Iba1 und TAL.1B5 analysiert. Zusätzlich erfolgte eine Untersuchung anhand des Filament Tracer. Stereologische Analysemethoden wurden zur Quantifizierung der Aβ-Ablagerungen und der Mikroglia angewandt. Disseminierte Plaques fanden sich bereits ab 9 Jahren. In den untersuchten Gehirnregionen von alten Hunden zeichnete sich ein progressiver Verlauf der Ablagerungen ab. Da insbesondere kleinere Hunde ein höheres Alter erreichten als mittelgroße und große Hunde konnten in dieser Kategorie vermehrt Plaques beobachtet werden. Den alten Tieren gemein war, dass in den untersuchten Gehirnregionen pE3Aβ-Plaques häufiger vorlagen als Plaques, die aus Aβ8-17 bestanden. Kleinere parenchymale und meningeale Gefäße des frontalen Kortex schienen besonders anfällig gegenüber pE3Aβ-Ablagerungen zu sein. Im entorhinalen Kortex von kleinen Hunden war die Menge an gefäßassoziierten Aβ8-17- und pE3Aβ-Ablagerungen annähernd gleich. Bei mittelgroßen und großen Hunden dominierte im entorhinalen Kortex und ventralen Hippokampus die Anzahl an gefäßassoziierten Aβ8-17-Ablagerungen. Bei kleinen Hunden existierten im ventralen Hippokampus signifikant mehr gefäßassoziierte Aβ8-17- als pE3Aβ-Ablagerungen. Hyperphosphoryliertes Tau fand sich in der Hippokampusformation von drei Hunden im Alter von 11 bzw. 15 Jahren. Der Schweregrad war unterschiedlich ausgeprägt, sodass nur ein Hund eine hochgradige Pathologie mit NFTs und neuritischen Plaques aufwies. Einhergehend mit dem Alter und einer assoziierten Proteinpathologie fanden sich Veränderungen der mikroglialen Morphologie. Neben ramifizierten Mikroglia lagen in den untersuchten Gehirnregionen aktivierte Mikroglia vor. Einige Mikroglia wiesen Zeichen einer Seneszenz auf und waren insbesondere in den Gehirnen von Hunden mit einer hochgradigen Aβ- bzw. Tau-Pathologie vorhanden. Zusammenfassend ist festzustellen, dass mit dieser Studie eine nähere Charakterisierung des caninen kognitiven Dysfunktionssyndroms erfolgte. Die Befunde sind von hoher translationaler Bedeutung und fördern die Etablierung des Hundes als natürliches Modelltier zur Untersuchung von Alterungsprozessen des Gehirns und für die Erforschung des initialen Stadiums der Alzheimer-Krankheit.:1 Einleitung 2 Literaturübersicht 2.1 Das canine kognitive Dysfunktionssyndrom 2.2 Pathogenese der Proteinablagerungen 2.2.1 Amyloid-Pathologie 2.2.2 Tau-Pathologie 2.3 Mikroglia 2.3.1 Ursprung und Formen 2.3.2 Die Rolle der Mikroglia beim Morbus Alzheimer 2.4 Assoziation des CCDS zum Morbus Alzheimer 3 Tiere, Material und Methoden 3.1 Hunde 3.2 Gehirnproben 3.2.1 Gewinnung und Kryofixierung der Gehirne 3.2.2 Makroskopische Untersuchung der Gehirne 3.2.3 Untersuchte Gehirnregionen 3.2.4 Histologische Färbungen 3.3 Immunohistochemische und Immunfluoreszenzfärbungen 3.3.1 Antikörper und Seren 3.3.2 Protokoll der ABC-Methode 3.3.3 Protokoll zur Immunfluoreszenz 3.3.4 Kontrollen 3.4 Auswertung der Färbungen 3.4.1 Deskriptive Analyse der Präparate 3.4.2 Quantitative Analyse der immunhistochemischen Befunde 3.4.3 Statistische Auswertung 4 Ergebnisse 4.1 Anamnestische Merkmale der Hunde 4.1.1 Gruppeneinteilung in Größen- und Gewichtskategorien 4.1.2 Altersverteilung 4.1.3 Symptomatik 4.2 Pathologisch-histologische Untersuchung der Gehirne 4.2.1 Altersabhängige pathologische Gehirnveränderungen 4.2.2 Anteil der grauen Substanz des frontalen Kortex 4.2.3 Pathologisch-histologische Charakterisierung ausgewählter Hirnareale 4.2.3.1 Kontrollgruppe 4.2.3.2 Gehirne der alten Hunde 4.2.3.3 Korrelation der altersassoziierten Neuropathologie mit der Größen- und Gewichtskategorie 4.2.3.4 Statistische Auswertung 4.3 Detektion, Charakterisierung und Quantifizierung des Aβ-Proteins 4.3.1 Immunhistochemische Darstellung des Aβ-Proteins 4.3.1.1 Kontrollgruppe 4.3.1.2 Altersassoziierte Verteilung der Aβ-Ablagerungen 4.3.2 Morphologie der Aβ-Ablagerungen 4.3.3 Assoziation der Aβ-Ablagerungen mit der Größen- und Gewichtskategorie 4.3.4 Histochemische Darstellung des Aβ-Proteins 4.3.5 Quantifizierung der Aβ-Ablagerungen 4.4 Immunhistologische Darstellung von Tau-Pathologien 4.4.1 Kontrollgruppe 4.4.2 Alte Hunde der Versuchsgruppen 4.5 Charakterisierung und Quantifizierung der Mikroglia 4.5.1 Darstellung der Mikroglia 4.5.1.1 Kontrollgruppe 4.5.1.2 Alte Hunde der Versuchsgruppen 4.5.2 Assoziation der mikroglialen Morphologie zu den Größen- und Gewichtskategorien der untersuchten Hunde 4.5.3 Auswertung morphologischer Parameter mit dem Filament Tracer 4.5.4 Quantifizierung der Mikroglia 4.5.4.1 Untersuchung der Anzahl der Mikroglia in Assoziation zur Neuropathologie 4.5.4.2 Untersuchung der Anzahl der Mikroglia in Assoziation zu den Größen- und Gewichtskategorien 4.5.5 Nachweis HLA DR-positiver Mikroglia 4.5.5.1 Kontrollgruppe 4.5.5.2 Alte Versuchshunde 5 Diskussion 5.1 Hundepopulation 5.2 Pathologisch-histologische Untersuchung der Gehirne 5.3 Aβ-Pathologie 5.3.1 Parenchymale Aβ-Plaques 5.3.2 Gefäßassoziiertes Aβ-Protein 5.4 Tau-Pathologie 5.4.1 Häufigkeit innerhalb der Hundepopulation und kritische Wertung der Färbemethodik 5.4.2 Zusammenhang der Tau-Pathologie mit den Aβ-Ablagerungen 5.5 Mikroglia 5.5.1 Unterschiede in der Anzahl der Mikroglia zwischen jungen und alten Hunden 5.5.2 Unterschiede der Morphologie der Mikroglia zwischen jungen und alten Hunden 5.5.3 Detektion von dystrophischen Mikroglia in den Gehirnen von alten Hunden 5.6 Schlussfolgerungen 5.7 Ausblick 6 Zusammenfassung 7 Summary 8 Literaturverzeichnis 9 Anhang 9.1 Tabellarische Übersichten zu den Studientieren 9.2 Protokoll der H&E-Färbung 9.3 Übersicht einzelner Ergebnisse des humanen Gewebes 9.4 Tabellarische Übersichten der verwendeten Materialien Abbildungsverzeichnis Tabellenverzeichnis / Dogs develop an age-associated cognitive dysfunction syndrome with several aspects resembling Alzheimer\\\''s disease. Affected animals show signs of dis-orientation in their familiar surroundings, dementia, and a disturbed circadian rhythm. The underlying neurodegenerative disease is associated with patho-logic changes in the brain including regularly deposition of β-pleated amyloid and rarely hyperphosphorylated tau accumulation. However, there have been no reports of the highly cytotoxic and modified pE3Aβ in the canine brain. Equally, altered microglial morphology has not been documented so far. For this study 24 euthanized thoroughbred dogs and mongrels of different ages were available. Five of these animals had an average age of 2.1 years and served as control group. The remaining 19 dogs were 8 to 19 years old. Accor-ding to their height and weight these dogs were divided into 3 different categories including small (≤ 10 kg), medium (11 - 25 kg) and large dogs (> 25 kg). Brains were dissected from the skulls and fixed in 4 % paraformaldehyde. Afterwards the frontal and entorhinal cortex as well as the hippocampal for-mation were isolated, vitrificated in 30 % sucrose solution and frozen to -80 °C by methylbutane. These regions were sliced into 40 µm thick sections and subsequently stained by immunohistology in order to detect deposits of Aβ8-17, pE3Aβ and hyperphosphorylated tau, respectively. Antibodies against Iba1 and TAL.1B5 were used to analyze microglial morphology and activation status. Additionally further investigations were made with the Filament Tracer of Imaris software. Stereological analysis methods served for the quantification of Aβ depositions and microglia. Disseminated Aβ plaques were detected in dogs from 9 years on. Within the examined brain regions of elderly dogs a progressive course of Aβ depositions was observed. Especially small dogs had a longer lifespan than medium and large dogs with the result that more plaques were deposited in the brains of small dogs. Elderly dogs had in common that pE3Aβ-plaques where more often located in the examined brain regions than plaques containing Aβ8-17. Minor parenchymal and meningeal vessels seemed to be susceptible especially to pE3Aβ depositions. The amount of vessel-associated Aβ8-17 and pE3Aβ in the entorhinal cortex of small dogs was almost equal. Within the entorhinal cortex of medium and large dogs the amount of vessel-associated Aβ8-17 predominated. The ventral hippocampus of small dogs showed significantly more vessel-associated Aβ8-17 than pE3Aβ depositions. Hyperphosphorylated tau was present in the hippocampal formations of 3 dogs with an age of 11 and 15 years, respectively. The degree of severity varied with the result that only one dog showed a high-grade pathology with development of NFTs and neuritic plaques. Accompanied by age and associated protein pathology altered microglial morphology was detected. Alongside with ramified microglia, activated cells were identified in the examined brain regions. Several microglia showed signs of senescence and were present in the brains of dogs with severe Aβ and tau pathology. Summarizing, this study facilitated a further characterization of the canine cognitive dysfunction syndrome. The results are of highly translational importance and encourage the establishment of the dog as a natural animal model for studying age-associated processes and the initial stage of Alzheimer’s disease.:1 Einleitung 2 Literaturübersicht 2.1 Das canine kognitive Dysfunktionssyndrom 2.2 Pathogenese der Proteinablagerungen 2.2.1 Amyloid-Pathologie 2.2.2 Tau-Pathologie 2.3 Mikroglia 2.3.1 Ursprung und Formen 2.3.2 Die Rolle der Mikroglia beim Morbus Alzheimer 2.4 Assoziation des CCDS zum Morbus Alzheimer 3 Tiere, Material und Methoden 3.1 Hunde 3.2 Gehirnproben 3.2.1 Gewinnung und Kryofixierung der Gehirne 3.2.2 Makroskopische Untersuchung der Gehirne 3.2.3 Untersuchte Gehirnregionen 3.2.4 Histologische Färbungen 3.3 Immunohistochemische und Immunfluoreszenzfärbungen 3.3.1 Antikörper und Seren 3.3.2 Protokoll der ABC-Methode 3.3.3 Protokoll zur Immunfluoreszenz 3.3.4 Kontrollen 3.4 Auswertung der Färbungen 3.4.1 Deskriptive Analyse der Präparate 3.4.2 Quantitative Analyse der immunhistochemischen Befunde 3.4.3 Statistische Auswertung 4 Ergebnisse 4.1 Anamnestische Merkmale der Hunde 4.1.1 Gruppeneinteilung in Größen- und Gewichtskategorien 4.1.2 Altersverteilung 4.1.3 Symptomatik 4.2 Pathologisch-histologische Untersuchung der Gehirne 4.2.1 Altersabhängige pathologische Gehirnveränderungen 4.2.2 Anteil der grauen Substanz des frontalen Kortex 4.2.3 Pathologisch-histologische Charakterisierung ausgewählter Hirnareale 4.2.3.1 Kontrollgruppe 4.2.3.2 Gehirne der alten Hunde 4.2.3.3 Korrelation der altersassoziierten Neuropathologie mit der Größen- und Gewichtskategorie 4.2.3.4 Statistische Auswertung 4.3 Detektion, Charakterisierung und Quantifizierung des Aβ-Proteins 4.3.1 Immunhistochemische Darstellung des Aβ-Proteins 4.3.1.1 Kontrollgruppe 4.3.1.2 Altersassoziierte Verteilung der Aβ-Ablagerungen 4.3.2 Morphologie der Aβ-Ablagerungen 4.3.3 Assoziation der Aβ-Ablagerungen mit der Größen- und Gewichtskategorie 4.3.4 Histochemische Darstellung des Aβ-Proteins 4.3.5 Quantifizierung der Aβ-Ablagerungen 4.4 Immunhistologische Darstellung von Tau-Pathologien 4.4.1 Kontrollgruppe 4.4.2 Alte Hunde der Versuchsgruppen 4.5 Charakterisierung und Quantifizierung der Mikroglia 4.5.1 Darstellung der Mikroglia 4.5.1.1 Kontrollgruppe 4.5.1.2 Alte Hunde der Versuchsgruppen 4.5.2 Assoziation der mikroglialen Morphologie zu den Größen- und Gewichtskategorien der untersuchten Hunde 4.5.3 Auswertung morphologischer Parameter mit dem Filament Tracer 4.5.4 Quantifizierung der Mikroglia 4.5.4.1 Untersuchung der Anzahl der Mikroglia in Assoziation zur Neuropathologie 4.5.4.2 Untersuchung der Anzahl der Mikroglia in Assoziation zu den Größen- und Gewichtskategorien 4.5.5 Nachweis HLA DR-positiver Mikroglia 4.5.5.1 Kontrollgruppe 4.5.5.2 Alte Versuchshunde 5 Diskussion 5.1 Hundepopulation 5.2 Pathologisch-histologische Untersuchung der Gehirne 5.3 Aβ-Pathologie 5.3.1 Parenchymale Aβ-Plaques 5.3.2 Gefäßassoziiertes Aβ-Protein 5.4 Tau-Pathologie 5.4.1 Häufigkeit innerhalb der Hundepopulation und kritische Wertung der Färbemethodik 5.4.2 Zusammenhang der Tau-Pathologie mit den Aβ-Ablagerungen 5.5 Mikroglia 5.5.1 Unterschiede in der Anzahl der Mikroglia zwischen jungen und alten Hunden 5.5.2 Unterschiede der Morphologie der Mikroglia zwischen jungen und alten Hunden 5.5.3 Detektion von dystrophischen Mikroglia in den Gehirnen von alten Hunden 5.6 Schlussfolgerungen 5.7 Ausblick 6 Zusammenfassung 7 Summary 8 Literaturverzeichnis 9 Anhang 9.1 Tabellarische Übersichten zu den Studientieren 9.2 Protokoll der H&E-Färbung 9.3 Übersicht einzelner Ergebnisse des humanen Gewebes 9.4 Tabellarische Übersichten der verwendeten Materialien Abbildungsverzeichnis Tabellenverzeichnis

Objective: To study awareness of cognitive dysfunction in patients with very mild Alzheimer’s disease (AD) and subjects with mild cognitive impairment (MCI). Methods: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were ≥24 in all cases. The discrepancy between the patients’ and caregivers’ estimations of impairments was taken as a measure of anosognosia. Results: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). Conclusions: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver’s assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE ≥24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

<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>

Background Alterations of mental status are characteristic of psychiatric disorders but may also result from a multitude of organic causes. Generally, physical examination and blood analysis are a part of basic psychiatric differential diagnostics, whereas more sophisticated procedures (for example, brain imaging) are applied only in cases with pathologic diagnostic findings. Our report challenges this approach by describing a case of glioblastoma multiforme presenting as postpartum depression without abnormalities in basic differential diagnostics. Case presentation A 28-year-old white woman who had been in outpatient treatment for postpartum depression was taken to the psychiatric emergency room. The psychopathological assessment, however, showed mild disorientation and severe deficits of long-term memory. Moreover, she complained of stabbing, bilateral headaches, but results of her physical examination and blood analysis were unremarkable. Magnetic resonance imaging of the brain was performed, which showed a contrast-enhanced mass lesion in the left frontal lobe. The patient underwent urgent tumor resection, and histologic results revealed an IDH-mutant glioblastoma multiforme. The patient was discharged with a substantially improved psychopathology and without neurological deficits. Conclusions This report adds to the evidence that postpartum depression may have organic causes in some cases, a fact that needs to be considered in the clinical setting. Atypical neurocognitive findings in a psychiatric interview may alone justify brain imaging, despite normal physical examination and blood analysis results.