Genetic and lifestyle influences on memory, brain structure, and dementia

This doctoral thesis investigated genetic, inflammatory, and lifestyle influences on cognition, brain structure, and dementia. The influence of TOMM40 polymorphisms (Study I), a PICALM, BIN1 and CLU genetic risk score (GRS; Studies II, III), and inflammatory cytokines (Study IV) was assessed, as well as potential interactions with physical activity (Studies II-IV). All studies were based on the Swedish National study on Aging and Care in Kungsholmen (SNAC-K), including a subsample that had participated in magnetic resonance imaging (MRI). In Study I, the influence of TOMM40 polymorphisms (rs11556505 and rs2075650) on episodic memory and hippocampal volume was investigated. There was no independent influence of TOMM40 polymorphisms on episodic memory and hippocampal volume. However, carriers of an APOE ε4 allele who also harbored TOMM40 risk alleles relied more heavily on hippocampal volume for episodic memory performance. Study II confirmed our hypothesis that high genetic risk (GRS >4) based on Alzheimer’s disease (AD) candidate genes (PICALM rs3851179, rs541458, BIN1 rs744373, and CLU rs11136000) was associated with worse episodic memory performance in non-demented older adults. Interestingly, there was an interaction between physical activity and GRS. The combination of physical inactivity and high genetic risk was most detrimental to memory performance, whereas a high GRS could be compensated for by physical activity. In Study III, we investigated if the same GRS was associated with incident dementia, primarily AD. Despite the associations with memory performance in Study II, there was no effect of GRS on incident dementia during a follow-up period of 6 years. Nonetheless, we did replicate previous work showing that physical inactivity is associated with increased risk of dementia. Study IV investigated the influence of inflammatory cytokines and physical activity on graymatter volume and global cognitive decline. Although there was no relation between inflammatory cytokines and brain volume, high levels of IL-12p40 in individuals who were physically inactive were associated with smaller lateral prefrontal cortex and hippocampal volumes, as well as with global cognitive decline over 6 years. This suggests that levels of inflammation may be especially detrimental for brain and cognitive integrity in individuals who are physically inactive. In summary, the studies in this thesis suggest that physical inactivity is associated with reduced episodic memory performance, compromised structural brain volume, and dementia risk. Moreover, physical inactivity in combination with a high GRS or systemic inflammation was especially detrimental to episodic memory as well as to frontal and hippocampal volumes, respectively

Promising Genetic Biomarkers of Preclinical Alzheimer's Disease: The Influence of APOE and TOMM40 on Brain Integrity

Finding biomarkers constitutes a crucial step for early detection of Alzheimer's disease (AD). Brain imaging techniques have revealed structural alterations in the brain that may be phenotypic in preclinical AD. The most prominent polymorphism that has been associated with AD and related neural changes is the Apolipoprotein E (APOE) ε4. The translocase of outer mitochondrial membrane 40 (TOMM40), which is in linkage disequilibrium with APOE, has received increasing attention as a promising gene in AD. TOMM40 also impacts brain areas vulnerable in AD, by downstream apoptotic processes that forego extracellular amyloid beta aggregation. The present paper aims to extend on the mitochondrial influence in AD pathogenesis and we propose a TOMM40-induced disconnection of the medial temporal lobe. Finally, we discuss the possibility of mitochondrial dysfunction being the earliest pathophysiological event in AD, which indeed is supported by recent findings

The lake-catchment systems of three Łęczna-Włodawa lakes with Cretaceous rocks in their catchment areas

Wydział Nauk Geograficznych i Geologicznych: Instytut Geografii Fizycznej i Kształtowania Środowiska PrzyrodniczegoGłównym celem rozprawy było wyjaśnienie złożonych procesów funkcjonowania układów zlewniowo-jeziornych trzech wybranych jezior łęczyńsko-włodawskich. Wyjaśnienie genezy procesów określających aktualny stan badanych układów zlewiowo-jeziornych, wymagało rozpoznania zarówno warunków zlewniowych jak i misowych. Badania prowadzono w latach hydrologicznych 2007-2009. Systematycznie rejestrowano parametry hydrologiczne wód powierzchniowych i podziemnych, cech atmosfery, litosfery, pedosfery oraz antroposfery. W pracy po raz pierwszy zestawiono równania bilansowe dla mis jezior Sumin, Rotcze i Syczyńskiego. Zrekonstruowano stopień wypełnienia mis w oparciu o plany batymetryczne z dwóch różnych okresów oraz przeanalizowano zmienność sezonową parametrów fizykochemicznych.We wszystkich zlewniach można było wyróżnić hydrogeologiczną dwudzielność. W części wierzchowinowo-stokowej, dominował warstwowo-szczelinowy sposób krążenia wód, natomiast w przyjeziernej części równinnej ruch wody był utrudniony, poprzez znaczne powierzchnie utworów słabo przepuszczalnych.Wszystkie badane zlewnie cechował podobny, reżim odpływu, z roztopowym maksimum wiosennym i drugim okresem zwiększonych przepływów po opadach letnich. Jeziora Rotcze i Sumin to akweny o wartościach odpływu typowych dla zlewni poleskich, natomiast Jezioro Syczyńskie miało parametry odpływu wód wyraźnie wyższe. Czas wymiany wody badanych jezior był także zróżnicowany. Najwolniej proces ten zachodził w największym jeziorze Sumin, najszybciej zaś wody wymieniały się w Jeziorze Syczyńskim.The main aim of the study was to explain multidirectional processes of lake-catchment system of chosen lakes. The subject was meaningful, taking into consideration that there are very few strictly hydrological papers concerning Łęczna-Włodawa Lakes. Territorial research was done during three water years 2007-2009.A condition of natural environment results mostly from human activity. The diverse methods were used to present complex relations among atmosphere, lithosphere, biosphere and anthroposphere. Hydrological, meteorological, lithosphere, pedosphere and anthroposphere parameters were observed continuously. A role of the factors that shape both qualitative and quantitative features of the three catchment areas was estimated using a comparative analysis. The functioning of catchments under study was determined by an interaction of hydrological (water budget, the pace of water exchange), hydrochemical (potential mineralization), and ecological processes. Water budget equations of lakes Sumin, Rotcze and Syczyńskie basins has been presented for the first time in this thesis. All the catchment areas under study were dual in terms of geological structure and relief. In the upper, eastern part of the catchment areas, water circulation was characteristic for fractured-porous mediums, while in the lower parts a pace of seepage was very low due to impervious rocks presence. A flow rate measured in catchments of lakes Rotcze and Sumin was typical of Polesie region, while in Syczyńskie the value of flow rate was significantly higher, similar to those observed in the Lublin Upland catchment

The lake-catchment systems of three Łęczna-Włodawa lakes with Cretaceous rocks in their catchment areas

Wydział Nauk Geograficznych i Geologicznych: Instytut Geografii Fizycznej i Kształtowania Środowiska PrzyrodniczegoGłównym celem rozprawy było wyjaśnienie złożonych procesów funkcjonowania układów zlewniowo-jeziornych trzech wybranych jezior łęczyńsko-włodawskich. Wyjaśnienie genezy procesów określających aktualny stan badanych układów zlewiowo-jeziornych, wymagało rozpoznania zarówno warunków zlewniowych jak i misowych. Badania prowadzono w latach hydrologicznych 2007-2009. Systematycznie rejestrowano parametry hydrologiczne wód powierzchniowych i podziemnych, cech atmosfery, litosfery, pedosfery oraz antroposfery. W pracy po raz pierwszy zestawiono równania bilansowe dla mis jezior Sumin, Rotcze i Syczyńskiego. Zrekonstruowano stopień wypełnienia mis w oparciu o plany batymetryczne z dwóch różnych okresów oraz przeanalizowano zmienność sezonową parametrów fizykochemicznych.We wszystkich zlewniach można było wyróżnić hydrogeologiczną dwudzielność. W części wierzchowinowo-stokowej, dominował warstwowo-szczelinowy sposób krążenia wód, natomiast w przyjeziernej części równinnej ruch wody był utrudniony, poprzez znaczne powierzchnie utworów słabo przepuszczalnych.Wszystkie badane zlewnie cechował podobny, reżim odpływu, z roztopowym maksimum wiosennym i drugim okresem zwiększonych przepływów po opadach letnich. Jeziora Rotcze i Sumin to akweny o wartościach odpływu typowych dla zlewni poleskich, natomiast Jezioro Syczyńskie miało parametry odpływu wód wyraźnie wyższe. Czas wymiany wody badanych jezior był także zróżnicowany. Najwolniej proces ten zachodził w największym jeziorze Sumin, najszybciej zaś wody wymieniały się w Jeziorze Syczyńskim.The main aim of the study was to explain multidirectional processes of lake-catchment system of chosen lakes. The subject was meaningful, taking into consideration that there are very few strictly hydrological papers concerning Łęczna-Włodawa Lakes. Territorial research was done during three water years 2007-2009.A condition of natural environment results mostly from human activity. The diverse methods were used to present complex relations among atmosphere, lithosphere, biosphere and anthroposphere. Hydrological, meteorological, lithosphere, pedosphere and anthroposphere parameters were observed continuously. A role of the factors that shape both qualitative and quantitative features of the three catchment areas was estimated using a comparative analysis. The functioning of catchments under study was determined by an interaction of hydrological (water budget, the pace of water exchange), hydrochemical (potential mineralization), and ecological processes. Water budget equations of lakes Sumin, Rotcze and Syczyńskie basins has been presented for the first time in this thesis. All the catchment areas under study were dual in terms of geological structure and relief. In the upper, eastern part of the catchment areas, water circulation was characteristic for fractured-porous mediums, while in the lower parts a pace of seepage was very low due to impervious rocks presence. A flow rate measured in catchments of lakes Rotcze and Sumin was typical of Polesie region, while in Syczyńskie the value of flow rate was significantly higher, similar to those observed in the Lublin Upland catchment

The Role of Confluence in Shaping Water Quality Parameters on Example of the Flow-Through Lake Bikcze (Eastern Poland)

The role of confluence (flowability) in shaping the concentration of dissolved oxygen (DO), chlorophyll-a (chl-a) and pH was determined using a model approach. The calculations considered both horizontal and vertical variability of parameters. There was a general tendency for the pH and oxygen to increase along the transect connecting the place of surface water inlet, deepest point of the lake basin and the place of water outlet, and the reverse tendency for chlorophyll. The average gradient for particulate radius was calculated as arithmetic mean value of six partial gradients (corresponding to individual depths, every 0.5 m). Values of average gradients indicated high dynamics of DO and pH concentration changes as well as low chlorophyll-a variability. A slight inclination of the final resultant vector gradients of DO and pH from the surface water inlet, deepest point of the lake basin and the place of water outlet transect indicated the dominant role of confluence in these parameters variability (values amounted to 6.08 mg·km−1 and 3.34 pH units·km−1, respectively). The value of the chlorophyll-a gradient vector (1.86 µg·km−1) indicated a slight differentiation of the parameter in the basin, independent of the hydrological conditions. The concentration of chl-a in the polymictic Lake Bikcze resulted from the effect of the limnic conditions; the flowability of the lake was just one of many factors affecting the variability of the parameter

Assessment of Spatial and Vertical Variability of Water Quality: Case Study of a Polymictic Polish Lake

UE regulations focus on methods of water quality monitoring and their use in rational management practices. This study investigated horizontal and vertical variations of electrical conductivity (EC), pH, dissolved oxygen (DO), and chlorophyll a (Chl-a) in a shallow polymictic lake. Monitoring of short-term variability of physical and chemical lake water parameters is a critical component in lake management, as it influences aquatic life. Based on the field research, maps of spatial distribution of the parameters were drawn. Using two methods: (1) a classical approach to water column measurements, from the top to the bottom (TB), in which the reference point is always a surface layer (SL), and (2) a newly introduced method of lake water quality monitoring based on a nearest neighbor (NN) approach; a comparison of higher and lower layers of the water column. By subtracting partial maps of spatial variability for different depths, final raster images were obtained. The NN method is rather absent in the limnology literature worldwide. Vertical and horizontal variability of the tested parameters in the polymictic, shallow Lake Bikcze (Poland) was presented in the results. In the presented paper, the commonly used TB method emphasized the role of the surface layer in shaping the variability of physicochemical parameters of lake waters. It shows a general trend of parameters’ changes from the top, to the bottom. The newly presented NN method, which has a major advantage in its simplicity and objectivity, emphasized structural differentiation within the range of variability. The nearest neighbor method was more accurate in showing the actual structure of fluctuation of parameters with higher fluctuation in the water column. Its advantage is a detailed recognition of the vertical variability of selected parameters in the water column. The method may be used regardless of the lake depth, its location in climatic zone, and/or region

Effects of Extracts Containing Metabolites of Different Cyanobacteria from an Ambient Spring (Central Europe) on Zooplankters Daphnia magna and Duckweed Spirodela polyrhiza

Toxic cyanobacterial blooms are a well-known problem in eutrophic water bodies, but cyanobacterial toxicity in ambient springs is unexplored. Therefore, we studied the toxin content and effects of two extracts obtained from epilithic and benthic microbial mats containing different algae and filamentous cyanobacteria, Phormidium breve and Oscillatoria limosa, respectively, on fresh biomass, number of roots, and pigment content in duckweed Spirodela polyrhiza and on survivorship of Daphnia magna (Cladocera). Mat samples, used to prepare extracts for bioassays, were collected in the anthropogenically transformed limnocrenic Górecko spring, located (50°31′08″ N and 22°57′10″ E) in the Roztocze region (Eastern Poland). It drains an abundant aquifer built with Cretaceous sediments. Neither anatoxin-a (ANTX) nor microcystins (MCs) were detected in the extracts using HPLC techniques; however, negative effects of the extracts on tested organisms were observed. The Phormidium extract contained concentrations of cyanobacterial metabolites a few times higher than the Oscillatoria extract. In general, both extracts affected plants in a dose-dependent manner; however, the Oscillatoria extract influenced pigment production without a clear trend. The highest concentrations of Phormidium extract (p < 0.05) significantly decreased the number of roots and the content of chlorophylls and carotenoids in S. polyrhiza. The Oscillatoria extract caused a statistically significant (p < 0.05) decrease in biomass and number of roots; however, it generally positively influenced the production of pigments. The extract containing O. limosa metabolites was more toxic to D. magna than the extract containing higher amounts of metabolites of P. breve. Cyanobacteria inhabiting temperate springs may negatively affect hydrobionts by producing secondary metabolites other than ANTX and MCs; however, the contribution of algae cannot be excluded. Extensive research on cyanobacteria in springs, their metabolites, and their effects on living organisms should be conducted

Role of Hydrology in Cyanobacterial Blooms in the Floodplain Lakes

River floodplains are sites of extremely high environmental and ecological value due to high biodiversity. Floodplain lakes (FPLs) are essential parts of complex floodplain ecosystems’ biological and hydro-chemical processes. Clear seasonal cycles, determined by the regime of the parent river and closely linked to climatic conditions, are observed in these lakes. Both the quantity and the quality of water are determined by the functional phases of a floodplain lake; limnophase, when the lake is isolated from the river, and potamophase (inundation), when the floodplain lake is overflowed by the river waters. These phases highly modify lake bathymetry, water balance, chemistry, and biology. Human pressure, mostly dam construction and land use changes, alter the frequency, duration, and intensity of natural cycles of inundation. The majority of large rivers in the Northern Hemisphere have been impacted by human activity. Floodplain lakes are also affected by continuous climate change, due to the alterations of the hydrological regimes. Cyanobacterial blooms in floodplain lakes are often characterized by high qualitative and quantitative annual and long-term variability. The main forces driving cyanobacterial blooms can be found in the flooding dynamics and intensity influencing hydraulic residence time and the concentration of biogenic compounds in lake water. Cyanotoxin production and seasonal dynamics in floodplain lakes have been rarely studied, particularly in connection with the hydrological regime. Moreover, the effects of cyanobacterial blooms and their toxicity to organisms inhabiting floodplain lakes, connected rivers, and floodplains are poorly understood. Therefore, knowledge of the processes controlling floodplain lakes’ ecological conditions is crucial to implementing water management and restoration practices, protecting those fragile and precious ecosystems from degradation and possible extension