Dopamine Receptor Genes Modulate Associative Memory in Old Age.

Previous research shows that associative memory declines more than item memory in aging. Although the underlying mechanisms of this selective impairment remain poorly understood, animal and human data suggest that dopaminergic modulation may be particularly relevant for associative binding. We investigated the influence of dopamine (DA) receptor genes on item and associative memory in a population-based sample of older adults (n = 525, aged 60 years), assessed with a face-scene item associative memory task. The effects of single-nucleotide polymorphisms of DA D1 (DRD1; rs4532), D2 (DRD2/ANKK1/Taq1A; rs1800497), and D3 (DRD3/Ser9Gly; rs6280) receptor genes were examined and combined into a single genetic score. Individuals carrying more beneficial alleles, presumably associated with higher DA receptor efficacy (DRD1 C allele; DRD2 A2 allele; DRD3 T allele), performed better on associative memory than persons with less beneficial genotypes. There were no effects of these genes on item memory or other cognitive measures, such as working memory, executive functioning, fluency, and perceptual speed, indicating a selective association between DA genes and associative memory. By contrast, genetic risk for Alzheimer disease (AD) was associated with worse item and associative memory, indicating adverse effects of APOE ε4 and a genetic risk score for AD (PICALM, BIN1, CLU) on episodic memory in general. Taken together, our results suggest that DA may be particularly important for associative memory, whereas AD-related genetic variations may influence overall episodic memory in older adults without dementia.

Physical activity and inflammation: effects on gray-matter volume and cognitive decline in aging.

Physical activity has been positively associated with gray-matter integrity. In contrast, pro-inflammatory cytokines seem to have negative effects on the aging brain and have been related to dementia. It was investigated whether an inactive lifestyle and high levels of inflammation resulted in smaller gray-matter volumes and predicted cognitive decline across 6 years in a population-based study of older adults (n = 414). Self-reported physical activity (fitness-enhancing, health-enhancing, inadequate) was linked to gray-matter volume, such that individuals with inadequate physical activity had the least gray matter. There were no overall associations between different pro-and anti-inflammatory markers (IL-1ß, IL-6, IL-10, IL-12p40, IL-12p70, G-CSF, and TNF-α) and gray-matter integrity. However, persons with inadequate activity and high levels of the pro-inflammatory marker IL-12p40 had smaller volumes of lateral prefrontal cortex and hippocampus and declined more on the Mini-Mental State Examination test over 6 years compared with physically inactive individuals with low levels of IL-12p40 and to more physically active persons, irrespective of their levels of IL-12p40. These patterns of data suggested that inflammation was particularly detrimental in inactive older adults and may exacerbate the negative effects of physical inactivity on brain and cognition in old age. Hum Brain Mapp 37:3462-3473, 2016. © 2016 Wiley Periodicals, Inc.

Genetics and underlying pathology of dementia.

As the population steadily ages, dementia, in all its forms, remains a great societal challenge. Yet, our knowledge of their etiology remains rather limited. To this end, genetic studies can give us insight into the underlying mechanisms that lead to the development of dementia, potentially facilitating treatments in the future. In this review we cover the most recent genetic risk factors associated with the onset of the four most common dementia types today, including Alzheimer's disease (AD), Vascular Dementia (VaD), Frontotemporal Lobar Degeneration (FTLD) and Lewy Body Dementia (LBD). Moreover, we discuss the overlap in major underlying pathologies of dementia derived from their genetic associations. While all four dementia types appear to involve genes associated with tau-pathology and neuroinflammation only LBD, AD and VaD appear to involve amyloid genes while LBD and FTLD share alpha synuclein genes. Together these findings suggest that some of the dementias may exist along a spectrum and demonstrates the necessity to conduct large-scale studies pinpointing the etiology of the dementias and potential gene and environment interactions that may influence their development.

Hydrochemical versus biological conditions of the functioning of three shallow lakes in Leczna-Wlodawa.

Lake-catchment relationships were presented with reference to each part of the subsystem. Ionic loads reflected the potential of the catchment areas and displayed the following pattern: Lake Rotcze < Lake Sumin < Lake Syczynskie; with respect to every ion, except nitrogen. The highest specific load of ions in Lake Syczynskie and the strong hydrochemical influence of the lake inlets facilitated the growth of water blooms of cyanobacteria, with a dominance of toxic filamentous P agardhii. It resulted in a poor ecological status of the lake (Q index = 0.8) and its hypertrophy (TSIchl-a = 78). The specific load of ions in the Lake Rotcze catchment (0.23 kg/yr-km(2) of P-PO4) contributed to the good ecological status (Q = 3.2) and mesotrophic character (TSIchl.a = 50) of the lake. Lake Sumin has a moderate catchment influence (2.41 kg/yr-km(2) of P-PO4), which facilitated moderate ecological (Q = 2.1) and trophic (eutrophy; TSIchlSa = 63) status.

Toys and gadgets: construct validity of apathy in Parkinson's disease.

Apathy is one of the primary neuropsychiatric signatures in Parkinson's disease, yet little research has addressed the construct validity of two commonly used apathy measures, the Apathy Scale and the Lille Apathy Rating Scale. The authors tested the hypothesis that apathy is associated with reduced initiative/engaged behaviors on a laboratory-based measure of apathy. Support was found for the hypothesis that apathy, as indexed by the Apathy Scale and the Lille Apathy Rating Scale, is associated with reduced initiative/engagement on an experimental measure of apathy in Parkinson's disease patients. These findings provide independent evidence for the construct validity of self-report apathy scales, beyond clinician judgment.

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.

Environmental implications of potamophases duration and concentration period in the floodplain lakes of the Bug River valley.

The Bug River, in the section between Dorohusk and Wlodawa (part of the eastern UE border), is one of the last remaining natural rivers in Europe. Thus, its abundance of floodplain lakes (FPL) in that part constitutes an area which preserves biodiversity. This study presents an analysis of potamophases duration and the Potamophases Concentration Index (PCI) in 20 floodplain lakes in the multi-year period 1952-2014. One-way analysis of variance (ANOVA, Tukey test), as well as a correlogram approach were used to perform statistical analyses. Among the lakes, few differed significantly from the others; more often, differences between years, in terms of both potamophase duration and PCI, were found. This proved that time is more important than space in shaping river valley hydrology. Cumulative values of the study indices, presented in a correlogram, showed that both potamophase duration and the period of potamophase concentration determine the water quality of a floodplain lake, expressed as the hydro-chemical type. In floodplain lakes with short potamophases concentrated at the beginning of a hydrologic year, water quality typical for interzonal lakes was observed; in floodplain lakes with the longest potamophases with their concentration at the end of a hydrologic year, ionic concentrations typical of extrazonal lakes occurred, whereas in lakes with a potamophase duration close to the average value and a spring concentration of floods, intermediate water quality was observed, typical of mixozonal lakes. A sound knowledge of floodplain lake functioning is crucial to maintaining the biodiversity of river valleys due to the lake's natural water and nutrient storage capacity.

Everyday functioning in Parkinson's disease: Evidence from the Revised-Observed Tasks of Daily Living (OTDL-R).

INTRODUCTION: Performance tasks are presumed to have greater validity than rating scales in assessing day-to-day behaviors in Parkinson's disease (PD). One such task is the revised Observed Tasks of Daily Living (OTDL-R), which has been used extensively in healthy older adults, and but not yet empirically examined in PD. Thus, the aims of the current study were to examine and determine the impact of cognitive, motor, and mood symptoms on OTDL-R performance in PD. METHOD: Nineteen non-demented PD patients and 18 healthy older adults (HC) were administered measures of mood and cognitive functioning, and the OTDL-R (subtests include medication and telephone use, and medication management). Clinical severity of PD was assessed using the H&Y stage, UPDRS, and Schwab and England functional disability scores. RESULTS: Mann Whitney U tests indicated the PD patients were significantly slower to complete the OTDL-R and performed worse on only the telephone use subtest, relative to the HC group. In the PD group, hierarchical regression analyses revealed memory, attention, and initiative/perseveration were uniquely associated with the financial management subtest, after controlling for motor severity (ps < .05). No other significant relationships were found. CONCLUSIONS: PD patients were slower to complete the OTDL-R, but only less accurate on the telephone use subtest. Poor performance on the telephone use subtest may be related to motor severity, while poor performance on the financial management subtest was related to attention and working memory. Overall, the findings warrant future investigation to determine the validity and reliability of the OTDL-R in PD.

Instability of Water Quality of a Shallow, Polymictic, Flow-Through Lake.

This paper describes catchment processes that favor the trophic instability of a shallow polymictic lake, in which a shift from eutrophy to hypertrophy occurs rapidly. In the lake, in 2007, the winter discharge maximum and an intensive precipitation (monthly sums exceeded 60 mm) in a vegetation season were observed. In 2007, the cyanobacterial blooms disappeared and the water trophy decreased. Total phosphorus (TP) was the main factor determining the high trophic status of the lake. The TP retention resulted from a quick flow of two inflows: QI1 (r = 0.64) and QI2 (0.56), and the base flow of tributary 1 (0.62). A significant negative correlation between TP and precipitation (r = - 0.54) was observed. Both the surface and the groundwater inflow of I4 showed a positive correlation with the retention of PO4 (r = 0.67 and r = 0.60, respectively), whereas the outlet discharge determined RNO3 (r = 0.57). The trophy of Lake Syczynskie was determined by the relationship between nutrient input and export, expressed as the ionic retention, Carlson's trophic state index (TSI), and phytoplankton abundance. The results showed that many factors influence the stability of water quality in small, polymictic lakes. However, in the studied lake, intense precipitation and winter discharge maxima (particularly base flow) prevented summer cyanobacterial blooms.

The benefits of staying active in old age: physical activity counteracts the negative influence of PICALM, BIN1, and CLU risk alleles on episodic memory functioning.

PICALM, BIN1, CLU, and APOE are top candidate genes for Alzheimer's disease, and they influence episodic memory performance in old age. Physical activity, however, has been shown to protect against age-related decline and counteract genetic influences on cognition. The aims of this study were to assess whether (a) a genetic risk constellation of PICALM, BIN1, and CLU polymorphisms influences cognitive performance in old age; and (b) if physical activity moderates this effect. Data from the SNAC-K population-based study were used, including 2,480 individuals (age range = 60 to 100 years) free of dementia at baseline and at 3- to 6-year follow-ups. Tasks assessing episodic memory, perceptual speed, knowledge, and verbal fluency were administered. Physical activity was measured using self-reports. Individuals who had engaged in frequent health- or fitness-enhancing activities within the past year were compared with those who were inactive. Genetic risk scores were computed based on an integration of risk alleles for PICALM (rs3851179 G allele, rs541458 T allele), BIN1 (rs744373 G allele), and CLU (rs11136000 T allele). High genetic risk was associated with reduced episodic memory performance, controlling for age, education, vascular risk factors, chronic diseases, activities of daily living, and APOE gene status. Critically, physical activity attenuated the effects of genetic risk on episodic memory. Our findings suggest that participants with high genetic risk who maintain a physically active lifestyle show selective benefits in episodic memory performance.

Genetic effects on old-age cognitive functioning: a population-based study.

Associations between genotypes and cognitive outcomes may provide clues as to which mechanisms cause individual differences in old-age cognitive performance. We investigated the effects of five polymorphisms on cognitive functioning in a population-based sample of 2,694 persons without dementia (60-102 years). A structural equation model (SEM) was fit to the cognitive data, yielding five specific latent factors (perceptual speed, episodic memory, semantic memory, category fluency, and letter fluency), as well as a global cognitive factor. These factors showed the expected associations with chronological age. Genotyping was performed for five single-nucleotide polymorphisms that have been associated with cognitive performance: APOE (rs429358), COMT (rs4680), BDNF (rs6265), KIBRA (rs17070145), and CLSTN2 (rs6439886). After controlling for age, gender, and education, as well as correcting for multiple comparisons, we observed negative effects of being an APOE ε4 carrier on episodic memory and perceptual speed. Furthermore, being a CLSTN2 TT carrier was associated with poorer semantic memory. For the global factor, the same pattern of results was observed. In addition, being a BDNF any A carrier was associated with better cognitive performance. Also, older age was associated with stronger genetic effects of APOE on global cognition. However, this interaction effect was partly driven by the presence of preclinical dementia cases in our sample. Similarly, excluding future dementia cases attenuated the effects of APOE on episodic memory and global cognition, suggesting that part of the effects of APOE on old-age cognitive performance may be driven by dementia-related processes.

The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age.

Mitochondrial dysfunction is implicated in neurodegenerative disorders, such as Alzheimer's disease (AD). Translocase of outer mitochondrial membrane 40 (TOMM40) may be influential in this regard by influencing mitochondrial neurotoxicity. Little is known about the influence of the TOMM40 gene on hippocampal (HC) volume and episodic memory (EM), particularly in healthy older adults. Thus, we sought to discern the influence of TOMM40 single nucleotide polymorphisms (SNPs), which have previously been associated with medial temporal lobe integrity (rs11556505 and rs2075650), on HC volume and EM. The study sample consisted of individuals from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) who were free of dementia and known neurological disorders, and 60-87 years of age (n = 424). EM was measured by using a 16-item word list with a 2-min free recall period and delineation of the HC was performed manually. The influence of Apolipoprotein E (APOE) and TOMM40 was assessed by 2 × 2 ANOVAs and partial correlations. There was no effect of APOE and TOMM40 on EM performance and HC volume. However, partial correlations revealed that HC volume was positively associated with free recall performance (r = 0.21, p < 0.01, r (2) = 0.04). When further stratified for TOMM40, the observed association between HC volume and free recall in APOE ε4 carriers was present in combination with TOMM40 rs11556505 any T (r = 0.28, p < 0.01, R (2) = 0.08) and rs2075650 any G (r = 0.28, p < 0.01, R (2) = 0.08) "risk" alleles. This pattern might reflect higher reliance on HC volume for adequate EM performance among APOE ε4 carriers with additional TOMM40 "risk" alleles suggesting that the TOMM40 gene cannot merely be considered a marker of APOE genotype. Nevertheless, neither APOE nor TOMM40 influenced HC volume or EM in this population-based sample of cognitively intact individuals over the age of 60.

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.