Bakgrund: Demens förekommer i många former och yttras på olika sätt i ett degenerativt förlopp. Globalt lider 55 miljoner människor av denna sjukdom. En majoritet av befolkningen blir alltmer äldre och behovet av omsorg ökar med avsaknad av tillräckligt med platser på särskilda boenden. Omsorgen sköts mer i det ordinära boendet med involvering av anhöriga vars tillvaro belastas och välbefinnande successivt försämras. Syfte: Belysa anhörigas upplevelser tiden efter att deras demenssjuke familjemedlem flyttat till särskilt boende. Metod: En litteraturöversikt av enbart kvalitativ forskning. Sökning av artiklar genomfördes i databaserna Cinahl och MedLine. En manifest kvalitativ innehållsanalys valdes av de 13 artiklar som ingick. Det analyserade materialet baserades på intervjuer. Resultat: Analysen av de anhörigas upplevelser resulterade i 3 teman. ”Emotionell belastning”, ”En ökad finansiell utmaning” och ”En harmonisk tillvaro”. I dessa teman framkommer ökad ensamhet, sorg, skuldkänslor, oroat samvete samt ekonomiska svårigheter. Slutsats: Tiden efter den närstående residerat i ny boendeform befinner sig anhöriga i en omvälvande fas i livet med stor omställning. En ofta redan tumult och svårt belastad tillvaro, övergår i ett skede med nya emotionellasvårigheter. / Background: Dementia manifests itself in different ways in the degenerative process. Globally, 55 million people suffer from this disease. A majority of the population is getting older and the need for care increases with the lack of nursing home facilities. Homebased care of dementia is more prevalent. Informal caregivers are commonly involved in care which gradually decreases their well-being. Aim: Elucidate informal caregivers’ experiences after nursing home admission of their relative with dementia. Method: A literature review of qualitative research. Articles were searched in the databases Cinahl and MedLine. A manifest qualitative content analysis was selected of the 13 articles that were included. The analyzed data was based on interviews. Results: The analysis of the relatives' experiences resulted in 3 themes. "Emotional burden", "An increased financial challenge" and "A harmonious existence". These themes identified increased loneliness, grief, guilt, troubled conscience and financial difficulties. Conclusion: Relatives are in an upheaval phase in life with major adjustment after their family member with dementia resides in the nursing home. An often already tumultuous and heavily burdened existence transitions into a stage with new emotional difficulties.

The deposition of β-amyloid peptides and of α-synuclein proteins is a neuropathological hallmark in the brains of Alzheimer’s disease (AD) and Parkinson’s disease (PD) subjects, respectively. However, there is accumulative evidence that both proteins are not exclusive for their clinical entity but instead co-exist and interact with each other. Here, we investigated the presence of a newly identified, pyroglutamate79-modified α-synuclein variant (pGlu79-aSyn)—along with the enzyme matrix metalloproteinase-3 (MMP-3) and glutaminyl cyclase (QC) implicated in its formation—in AD and in the transgenic Tg2576 AD mouse model. In the human brain, pGlu79-aSyn was detected in cortical pyramidal neurons, with more distinct labeling in AD compared to control brain tissue. Using immunohistochemical double and triple labelings and confocal laser scanning microscopy, we demonstrate an association of pGlu79-aSyn, MMP-3 and QC with β-amyloid plaques. In addition, pGlu79-aSyn and QC were present in amyloid plaque-associated reactive astrocytes that were also immunoreactive for the chaperone heat shock protein 27 (HSP27). Our data are consistent for the transgenic mouse model and the human clinical condition. We conclude that pGlu79-aSyn can be generated extracellularly or within reactive astrocytes, accumulates in proximity to β-amyloid plaques and induces an astrocytic protein unfolding mechanism involving HSP27.

Background. Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) may have different effects on cognitive health due to their anti- or pro-inflammatory properties. Methods. We aimed to prospectively examine the relationships between n-3 and n-6 PUFA contents in serum phospholipids with incident all-cause dementia and Alzheimer’s disease dementia (AD). We included 1264 non-demented participants aged 84 ± 3 years from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) multicenter-cohort study. We investigated whether fatty acid concentrations in serum phospholipids, especially eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA), were associated with risk of incident all-cause dementia and AD. Results. During the follow-up window of seven years, 233 participants developed dementia. Higher concentrations of EPA were associated with a lower incidence of AD (hazard ratio (HR) 0.76 (95% CI 0.63; 0.93)). We also observed that higher concentrations of EPA were associated with a decreased risk for all-cause dementia (HR 0.76 (95% CI 0.61; 0.94)) and AD (HR 0.66 (95% CI 0.51; 0.85)) among apolipoprotein E ε4 (APOE ε4) non-carriers but not among APOE ε4 carriers. No other fatty acids were significantly associated with AD or dementia. Conclusions. Higher concentrations of EPA were associated with a lower risk of incident AD. This further supports a beneficial role of n-3 PUFAs for cognitive health in old age.

Based on a targeted literature review, this vision paper emphasizes the importance of dementia-sensitive built space. The article specifically focuses on supporting spatial orientation and wayfinding for people living with dementia. First, we discuss types of wayfinding challenges, underlying processes, and consequences of spatial disorientation in the context of dementia of the Alzheimer’s type. Second, we focus on current efforts aimed at planning and evaluating dementia-sensitive built space, i.e., environmental design principles, interventions, evaluation tools, strategies, and planning processes. Third, we use our findings as a starting point for developing an interdisciplinary research vision aimed at encouraging further debates and research about: (1) the perspective of a person with dementia, specifically in the context of wayfinding and spatial orientation, and (2) how this perspective supplements planning and design processes of dementia-sensitive built space. We conclude that more closely considering the perspective of people with dementia supports the development of demographically sustainable future cities and care institutions.

The classic surfactant proteins (SPs) A, B, C, and D were discovered in the lungs, where they contribute to host defense and regulate the alveolar surface tension during breathing. Their additional importance for brain physiology was discovered decades later. SP-G, a novel amphiphilic SP, was then identified in the lungs and is mostly linked to inflammation. In the brain, it is also present and significantly elevated after hemorrhage in premature infants and in distinct conditions affecting the cerebrospinal fluid circulation of adults. However, current knowledge on SP-G-expression is limited to ependymal cells and some neurons in the subventricular and superficial cortex. Therefore, we primarily focused on the distribution of SP-G-immunoreactivity (ir) and its spatial relationships with components of the neurovascular unit in murine forebrains. Triple fluorescence labeling elucidated SP-G-co-expressing neurons in the habenula, infundibulum, and hypothalamus. Exploring whether SP-G might play a role in Alzheimer’s disease (AD), 3xTg-AD mice were investigated and displayed age-dependent hippocampal deposits of β-amyloid and hyperphosphorylated tau separately from clustered, SP-G-containing dots with additional Reelin-ir—which was used as established marker for disease progression in this specific context. Semi-quantification of those dots, together with immunoassay-based quantification of intra- and extracellular SP-G, revealed a significant elevation in old 3xTg mice when compared to age-matched wildtype animals. This suggests a role of SP-G for the pathophysiology of AD, but a confirmation with human samples is required.

ATP is a (co)transmitter and signaling molecule in the CNS. It acts at a multitude of ligand-gated cationic channels termed P2X to induce rapid depolarization of the cell membrane. Within this receptor-channel family, the P2X7 receptor (R) allows the transmembrane fluxes of Na+, Ca2+, and K+, but also allows the slow permeation of larger organic molecules. This is supposed to cause necrosis by excessive Ca2+ influx, as well as depletion of intracellular ions and metabolites. Cell death may also occur by apoptosis due to the activation of the caspase enzymatic cascade. Because P2X7Rs are localized in the CNS preferentially on microglia, but also at a lower density on neuroglia (astrocytes, oligodendrocytes) the stimulation of this receptor leads to the release of neurodegeneration-inducing bioactive molecules such as pro-inflammatory cytokines, chemokines, proteases, reactive oxygen and nitrogen molecules, and the excitotoxic glutamate/ATP. Various neurodegenerative reactions of the brain/spinal cord following acute harmful events (mechanical CNS damage, ischemia, status epilepticus) or chronic neurodegenerative diseases (neuropathic pain, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis) lead to a massive release of ATP via the leaky plasma membrane of neural tissue. This causes cellular damage superimposed on the original consequences of neurodegeneration. Hence, blood-brain-barrier permeable pharmacological antagonists of P2X7Rs with excellent bioavailability are possible therapeutic agents for these diseases. The aim of this review article is to summarize our present state of knowledge on the involvement of P2X7R-mediated events in neurodegenerative illnesses endangering especially the life quality and duration of the aged human population.

The accuracy of neuropsychological assessment is critical in the diagnosis of cognitive impairments in older adults. However, existing neuropsychological tests may not be suitable for minority populations. This thesis aimed to address this issue by recruiting cognitively-healthy South Asian older adults and assessing cognitive function in this group. Results showed that typically used assessments, despite being translated, were not suitable for this cohort. Furthermore, skills required for test completion such as mathematics and writing/hand dexterity (which are related to education levels) influenced test scores. Therefore, new assessments of general cognitive function and associative memory were developed to improve the accuracy of neuropsychological test scores. The new tests were not affected by education and they achieved high internal and test re-test reliability. Time of day (TOD) that testing takes place is also known to affect cognition. Interestingly, no TOD effects were observed in this cohort. It was hypothesised that engagement in the daily five Islamic prayers may have contributed to this lack of a TOD effect. However, the results did not confirm this. The thesis then looked at overall prayer engagement and cognition. Results showed that engagement in the daily five prayers and Quran recitation significantly increased scores on assessments of processing speed. This thesis demonstrates that accurately assessing cognition in South Asian older adults is challenging and that the cognitive tests used must be suitable for this cohort. Interesting findings emerged for prayer engagement which may have wider implications for the field of cognitive reserve.

Les maladies neurodégénératives d’Alzheimer et de Parkinson sont caractérisées par des agrégats des peptides des amyloïdes-beta (Aβ) et l’alpha synucléine (αSyn), respectivement. L’agrégation de ces peptides solubles donne les matériels insolubles (les amyloïdes) sous forme de fibrilles et de plaques. L’agrégation de ces amyloïdes insolubles cause de la toxicité cellulaire dans le cerveau provoquant les effets neurodégénératifs. Les D, L-α-cyclopeptides synthétiques (e. g., CP-2, c-[leu-Nle-trp-His-ser-Lys]) furent synthétisés précédemment par le groupe de Rahimipour. Ils sont capables de former des nanotubes par pont hydrogène capables d’inhiber l’activité néfaste des amyloïdes. Les azapeptides utilisent de semicarbazide comme un substituant d’amide aminé. Insérés dans le D, L-α-cyclopeptide CP-2, les aza-résidus permettent d’améliorer la basicité de Lewis et l’acidité de Bronsted du peptide pour obtenir des ponts hydrogènes plus forts. Les azapeptides [azaNle3]-CP-2, [azaHse6]-CP-2 et [azaGly6]-CP-2 offrent d’excellents résultats au niveau des tests biologiques pour inhiber l’activité des amyloïdes ainsi que pour réduire la mortalité cellulaire en présence d’amyloïdes. À partir de ces résultats prometteurs, l’insertion de deux azapeptides dans un D, L-α-cyclopeptide a été effectué. En remplaçant l’histidine par l’alanine pour éviter des problèmes d’épimérisation, quatre nouveaux diazacyclopeptides ont été synthétisés en insérant les aza-résidus : l’aza-norleucine (azaNle), l’aza-homoserine (azaHse) et l’azaglycine (azaGly). Leur synthèse ainsi que leur caractérisation biophysique préliminaire seront présentés. / Alzheimer's and Parkinson's diseases are neurodegenerative diseases characterized by the aggregation of the peptides amyloid-beta (Aβ) and alpha-synuclein (Synα), respectively. The aggregation of these soluble peptides gives insoluble peptides (amyloids) in the forms of fibrils and plaques. Aggregation of insoluble amyloids can cause cellular toxicity in the brain resulting in neurodegenerative effects. Certain synthetic cyclic D,L-alpha-peptides (e.g., CP-2, c-[leu-Nle-trp-His-ser-Lys]) were previously synthesized by the Rahimipour laboratory and shown to form intermolecular hydrogen bonds and self-assemble into nanotubes capable of inhibiting the aggregation and harmful effects of amyloids. Azapeptides employ semicarbazides as amino amide surrogates. Insertion of aza-residues into the D,L-α-cyclopeptide CP-2 was explored to alter the Lewis basicity and Bronsted acidity of the peptide and improve hydrogen bonding potential. The azapeptides [azaNle3]-CP-2, [azaHse6]-CP-2, and [azaGly6]-CP-2 inhibited effectively amyloid aggregation and reduced amyloid-induced cell death. Based on the promising results of single aza-residue substitutions, the insertion of two aza-residues into D,L-α- cyclopeptide CP-2 analogs was investigated. Histidine was replaced with alanine to minimize epimerization. Four new diazacyclopeptides were synthesized by inserting aza-norleucine (azaNle), aza-homoserine (azaHse) and aza-glycine (azaGly). The syntheses and preliminary biophysical characterizations of the diazacyclopeptides will be presented.

Introduktion/Bakgrund: Demenssjukdom är ett spektrum av neurodegenerativa tillstånd som kännetecknas avgradvis kognitiv försämring. Globalt påverkar demenssjukdom miljontals äldre individer och deras omgivning.Oral hälsa är ofta förbisedd i vårdprocesser kring demenssjukdom. Orala hälsa är viktig för livskvaliteten. Sämreoral hälsa kan leda till sämre livskvalitet, smärta och påverkan på allmänhälsan. Munhälsointerventioner är därförviktiga för att förbättra livskvaliteten och minska riskerna för orala hälsoproblem.Syfte: Att kartlägga munhälsofrämjande interventioner riktade mot äldre individer med demenssjukdom.Frågeställningar: Vilka interventioner riktas mot demenssjuka för att främja deras orala hälsa? Vilka aktöreransvarar för genomförandet av interventionerna?Metod: En litteraturstudie genomfördes för att systematiskt granska och sammanställa befintlig forskning ochkunskap om ämnet. Databaserna PubMed och CINAHL användes. Analys genomfördes med hjälp avgranskningsmallar för att bedöma kvaliteten på de inkluderade studierna.Resultat: Utbildning för vårdpersonal och samarbetsbaserade strategier med vårdpartners ledde till bättre oralhygien och livskvalitet för äldre individer med demenssjukdom. Resultaten visade att enkla, regelbundna insatsersom tandborstningstekniker och kommunikationsträning hade positiva effekter på oral hälsa och välbefinnandebland äldre individer med demenssjukdom. Samarbete mellan tandvårdspersonal, vårdpersonal och vårdpartnersförbättrade den orala hälsan hos äldre individer med demenssjukdom.Slutsats: Äldre individer med demenssjukdom har ofta haft bristande oral hälsa. För att förbättra den orala hälsanhos äldre individer med demenssjukdomar är det viktigt att vara medveten om att det är ett komplext vårdpanoramasom äldre individer vårdas inom. Interventioner på en mer övergripande nivå, såsom syftar till att etablerasamarbete i strategier, tycks vara ett utvecklingsområde.

Alzheimer's disease (AD) and Parkinson's disease (PD), including dementia with Lewy bodies (DLB), account for the majority of dementia cases worldwide. Interestingly, a significant number of patients have clinical and neuropathological features of both AD and PD, i.e., the presence of amyloid deposits and Lewy bodies in the neocortex. The identification of α-synuclein peptides in amyloid plaques in DLB brain led to the hypothesis that both peptides mutually interact with each other to facilitate neurodegeneration. In this article, we report the influence of Aβ(1-42) and pGlu-Aβ(3-42) on the aggregation of α-synuclein in vitro. The aggregation of human recombinant α-synuclein was investigated using thioflavin-T fluorescence assay. Fibrils were investigated by means of antibody conjugated immunogold followed by transmission electron microscopy (TEM). Our data demonstrate a significantly increased aggregation propensity of α-synuclein in the presence of minor concentrations of Aβ(1-42) and pGlu-Aβ(3-42) for the first time, but without effect on toxicity on mouse primary neurons. The analysis of the composition of the fibrils by TEM combined with immunogold labeling of the peptides revealed an interaction of α-synuclein and Aβ in vitro, leading to an accelerated fibril formation. The analysis of kinetic data suggests that significantly enhanced nucleus formation accounts for this effect. Additionally, co-occurrence of α-synuclein and Aβ and pGlu-Aβ, respectively, under pathological conditions was confirmed in vivo by double immunofluorescent labelings in brains of aged transgenic mice with amyloid pathology. These observations imply a cross-talk of the amyloid peptides α-synuclein and Aβ species in neurodegeneration. Such effects might be responsible for the co-occurrence of Lewy bodies and plaques in many dementia cases.