Biochemical profiling and antioxidant activity analysis of commercially relevant seaweeds from northwest Europe.

BACKGROUND: The drive towards ensuring the sustainability of bioresources has been linked with better valorising primary materials and developing biorefinery pipelines. Seaweeds constitute valuable coastal resources with applications in the bioenergy, biofertiliser, nutrition, pharmaceutical and cosmetic sectors. Owing to the various sought-after metabolites they possess, several seaweed species are commercially exploited throughout Western Europe, including Ireland. Here, four commercially relevant brown (Fucus serratus and Fucus vesiculosus) and red (Chondrus crispus and Mastocarpus stellatus) seaweed species were sampled during a spring tide in July 2021 on moderately exposed shores across three coastal regions in the west of Ireland. RESULTS: Significant regional differences were identified when specimens were analysed for carbohydrates (max. 80.3 µg glucose eq mg-1 DW), proteins (max. 431.3 µg BSA eq. mg-1 DW), lipids (max. 158.6 mg g-1 DW), pigment signature and antioxidant potential. Protein content for F. serratus recorded a twofold difference between northern and southern specimens. The antioxidant potential of F. vesiculosus and M. stellatus returned greater activity compared to F. serratus and C. crispus, respectively. Multivariate analysis showed a clear latitudinal pattern across the three western coastal regions (north, west and south) for both F. vesiculosus and F. serratus. CONCLUSION: F. vesiculosus thalli from the northwest were richer in pigment content while the F. serratus thalli from the northwest were richer in antioxidants. Such biogeographic patterns in the biochemical make-up of seaweeds need consideration for the development of regional integrated aquaculture systems and the optimisation of the biomass content for targeted downstream applications. © 2024 Society of Chemical Industry.

Psychometric Evaluation of the A-NKS: A Diagnostic Instrument to Assess Impairment of Activities of Daily Living in Mild and Major Neurocognitive Disorder According to DSM-5.

BACKGROUND: Activities of daily living (ADL) functioning are important in the diagnosis of neurocognitive disorders (NCD), yet no standardized and validated instrument exist based on international classification systems. OBJECTIVE: We aimed to psychometrically evaluate the differentiated assessment of ADL and instrumental ADL (IADL) impairments due to NCD according to DSM-5 criteria (Instrument für die Erfassung von Alltagsbeeinträchtigungen bei Neurokognitiven Störungen; A-NKS). METHODS: We conducted a pilot study involving 92 participant-informant dyads of participants with mild or major NCDs, cognitively healthy individuals, and an informant, to test acceptability, internal consistency, and convergent validity with similar measures. RESULTS: Both A-NKS versions demonstrated excellent internal consistency (α= 0.95 -0.99) and correlate with other instrumental ADL instruments (participant [informant]: Barthel Index: rs = -0.26, p≤0.05 [rs = -0.30, p≤0.01]; Amsterdam IADL: rs = 0.59, p≤0.01 [rs = 0.48, p≤0.01]; SIDAM ADL: rs = 0.46, p≤0.001 [rs = 0.47, p≤0.001]). Additionally, there are correlations with the scale autonomy of the WHOQOL-OLD (rs = -0.50, p≤0.001 [rs = -0.37, p≤0.001]) and physical, as well as cognitive activities (rs = -0.39, p≤0.001 [rs = -0.50, p≤0.001]). They were well-accepted by participants and informants. CONCLUSIONS: The A-NKS is an instrument with acceptable psychometric properties to assess ADL due to neurodegenerative decline in healthy individuals, and those with mild or major NCD. Further research is needed to confirm reliability and validity and investigate the factor structure.

Strategies of adults for dealing with feelings of guilt - findings from a large web-based survey.

BACKGROUND: Feelings of guilt are common in adulthood. Depending on the situation, individuals need different strategies for dealing with these usually unpleasant experiences. The aim of this study was to provide comprehensive empirical information about such different guilt-related strategies used in adulthood. PARTICIPANTS AND PROCEDURE: A cross-sectional web-based survey was conducted (05/2019-04/2020) collecting autobiographical information on guilt experiences. Stated strategies for dealing with feelings of guilt were classified into inductively defined categories, and the frequency of the categorized strategies was calculated (total, gender-, age-specific). Associations between applied strategies and gender and age were analyzed using Cramér's φ and V as appropriate. RESULTS: Analyzing statements of 579 participants (18-84 years), we differentiated 34 different categories of guilt-related strategies. The most frequently used strategies were "Self-reflection; contemplation; analyzing/reviewing things one feels guilty about" and "Repressing/ignoring/(actively) forgetting/not thinking about/bottling up the feelings of guilt". Female and male participants showed a significantly different use only in the strategy of utilizing "Professional support/therapy/counseling" (10.57% vs. 3.67%; Cramér's φ = .13, p = .001). Additionally, only a few differences were found with regard to age. CONCLUSIONS: Adults use a broad variety of different strategies for dealing with feelings of guilt. Strategies regulating emotional responses to the problem causing feelings of guilt seem to be at least as important as strategies targeting the problem itself. Many strategies do not serve pro-social functions. Feelings of guilt are an issue relevant for mental health care since several of the adults with feelings of guilt utilize professional help, and an even higher number may need such help.

Linking self-perceived cognitive functioning questionnaires using item response theory: The subjective cognitive decline initiative.

OBJECTIVE: Self-perceived cognitive functioning, considered highly relevant in the context of aging and dementia, is assessed in numerous ways-hindering the comparison of findings across studies and settings. Therefore, the present study aimed to link item-level self-report questionnaire data from international aging studies. METHOD: We harmonized secondary data from 24 studies and 40 different questionnaires with item response theory (IRT) techniques using a graded response model with a Bayesian estimator. We compared item information curves to identify items with high measurement precision at different levels of the self-perceived cognitive functioning latent trait. Data from 53,030 neuropsychologically intact older adults were included, from 13 English language and 11 non-English (or mixed) language studies. RESULTS: We successfully linked all questionnaires and demonstrated that a single-factor structure was reasonable for the latent trait. Items that made the greatest contribution to measurement precision (i.e., "top items") assessed general and specific memory problems and aspects of executive functioning, attention, language, calculation, and visuospatial skills. These top items originated from distinct questionnaires and varied in format, range, time frames, response options, and whether they captured ability and/or change. CONCLUSIONS: This was the first study to calibrate self-perceived cognitive functioning data of geographically diverse older adults. The resulting item scores are on the same metric, facilitating joint or pooled analyses across international studies. Results may lead to the development of new self-perceived cognitive functioning questionnaires guided by psychometric properties, content, and other important features of items in our item bank. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Study protocol: Hypersexual and hyposexual behavior among adults diagnosed with alcohol- and substance use disorders-Associations between traumatic experiences and problematic sexual behavior.

Background: Hypersexual and hyposexual behaviors are common concomitant of substance use disorders (SUD). On the one hand, the regular consumption of alcohol or illegal drugs can lead to hypersexual or hyposexual behavior due to its effects on the organism; on the other hand, the use of psychotropic substances is also used as a coping strategy concerning already existing sexual impairments. The aforementioned disorders show similarities in terms of their etiology, as traumatic experiences get special attention as potential risk factors for the development of addictions, hypersexual, and hyposexual behavior. Objectives: The study aims to explore the association between SUD characteristics and hypersexual/hyposexual behavior, and a potential moderating effect of early traumatic life events by answering the following research questions: (1) Do people with SUD differ from a sample of people with other psychiatric disorders regarding hypersexual and hyposexual behavior? (2) What are the associations between the presence of sexual problems and different characteristics of the SUD (e.g., mono vs. polysubstance use, type of addictive substance, intensity of the disorder)? (3) What influence do traumatic experiences in childhood and adolescence have on the existence of sexual disorders among adults with a diagnosed SUD? Method: The target group of this cross-sectional ex-post-facto study comprises adults diagnosed with an alcohol- and/or substance use disorder. Data will be collected with an online survey, which will be promoted via several support and networking services for people diagnosed with SUD. Two control groups will be surveyed, one consisting of people with other psychiatric disorders than SUD and traumatic experiences, and one healthy group. Relations between the dependent variables (hypersexual and hyposexual behavior) and independent variables (sociodemographic information, medical and psychiatric status, intensity of the prevalent SUD, traumatic experiences, and symptoms of posttraumatic stress disorder) will be initially calculated via correlations and linear regression. Risk factors will be identified via multivariate regression. Discussion: Gaining relevant knowledge promises new perspectives for prevention, diagnosis, case conception, and therapy of SUDs as well as problematic sexual behaviors. The results can provide more information about the importance of psychosexual impairments regarding the development and maintenance of SUDs.

Short report: A trend analysis of attitudes towards early diagnosis of dementia in Germany.

BACKGROUND: Early detection of dementia provides numerous benefits for those living with dementia and their relatives and healthcare systems at large. Methods available for early diagnosis have improved significantly over the past years. Therefore, we examined whether support for offering an early diagnosis of dementia and willingness to pursue a respective early diagnosis have changed in Germany over the last decade. METHOD: We compared findings from two representative telephone surveys conducted among older adults in Germany (≥ 60 years of age) in 2011 and 2022, assessing support for offering an early diagnosis of dementia and willingness to pursue a respective early diagnosis in a sample of n = 879 individuals (mean age: 72.9, range: 60-98 years, % female: 58.8). Group comparisons using Chi2- and t-tests and multivariable regression analyses were conducted, regressing support of an early diagnosis of dementia and willingness to pursue a respective early diagnosis on age, gender, education, employment status, belief in preventability of dementia and time of survey. RESULTS: Support for offering an early diagnosis of dementia was high both in 2011 (90.7%) and 2022 (79.2%), but declined over time (OR: .39; 95% CI: .25; .63). Willingness to pursue an early diagnosis of dementia declined from 70.7% to 60.1% in the same period (OR: .62; 95% CI: .45; .86). Belief in preventability of dementia was linked to support for offering an early diagnosis (OR: 1.88, 95% CI: 1.25; 2.83) and willingness to pursue an early diagnosis of dementia (OR: 1.52; 95% CI: 1.12; 2.07). Older participants less often supported offering an early diagnosis of dementia (OR: .97, 95% CI: .95; .99). CONCLUSION: Support for offering an early diagnosis of dementia and willingness to pursue a respective diagnosis is high in the older German public, but lower than reported previously. Improving knowledge on modifiable risk factors and better understanding of individual motives underlying endorsement or refusal of an early diagnosis may increase acceptance in the general public.

Increased Serum NSE and S100B Indicate Neuronal and Glial Alterations in Subjects Under 71 Years With Mild Neurocognitive Disorder/Mild Cognitive Impairment.

Background: Mild cognitive impairment (MCI) is considered a pre-stage of different dementia syndromes. Despite diagnostic criteria refined by DSM-5 and a new term for MCI - "mild neurocognitive disorder" (mild NCD) - this diagnosis is still based on clinical criteria. Methods: To link mild NCD to the underlying pathophysiology we assessed the degree of white matter hyperintensities (WMH) in the brain and peripheral biomarkers for neuronal integrity (neuron-specific enolase, NSE), plasticity (brain-derived neurotrophic factor, BDNF), and glial function (S100B) in 158 community-dwelling subjects with mild NCD and 82 healthy controls. All participants (63-79 years old) were selected from the Leipzig-population-based study of adults (LIFE). Results: Serum S100B levels were increased in mild NCD in comparison to controls (p = 0.007). Serum NSE levels were also increased but remained non-significant after Bonferroni-Holm correction (p = 0.04). Furthermore, age by group interaction was significant for S100B. In an age-stratified sub-analysis, NSE and S100B were higher in younger subjects with mild NCD below 71 years of age. Some effects were inconsistent after controlling for potentially confounding factors. The discriminatory power of the two biomarkers NSE and S100B was insufficient to establish a pathologic threshold for mild NCD. In subjects with mild NCD, WMH load correlated with serum NSE levels (r = 0.20, p = 0.01), independently of age. Conclusion: Our findings might indicate the presence of neuronal (NSE) and glial (S100B) injury in mild NCD. Future studies need to investigate whether younger subjects with mild NCD with increased biomarker levels are at risk of developing major NCD.

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning.

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

The wide variety of reasons for feeling guilty in adults: findings from a large cross-sectional web-based survey.

BACKGROUND: Experiencing some sort of guilt is a common phenomenon in adulthood. As feeling guilty is usually unpleasant and may even lead to further negative psychological consequences like depression, the aim of this study was to provide comprehensive information on the reasons for such feelings in adults. METHODS: A cross-sectional web-based survey was conducted between May 2019 and April 2020, collecting qualitative information on reasons for feeling guilty in n = 604 adults (mean/SD age = 45.3/16.4 years; n = 346/57.3% women, n = 255/42.2% men and n = 3/0.5% adults without identification with a particular gender). Stated reasons were inductively classified into (super-)/categories, and information on frequency and percentage (total, gender- and age-specific) for each of these (super-)/categories was provided. RESULTS: Participants altogether stated 1515 reasons for feeling guilty that were classified into 12 supercategories and 49 categories. "Telling lies/withholding truth/information" followed by "Not spending (enough) time with family (members)/Not taking (enough) care of family (members)/not being there for family (members)" were the most frequent categories of reasons for feeling guilty in the sample. Guilt feelings explicitly referring to "religious beliefs" or a "subjectively perceived more general responsibility'" (e.g., for society, humankind, problems of the world), by contrast, were of minor importance. Male and female participants as well as participants of different ages showed similarities but also several differences in stated reasons for feeling guilty. Female participants, for example, more often experienced feelings of guilt related to family members, children and to some kind of general responsibility for the wellbeing of others, whereas male participants felt guilty more often because of some kind of misconduct/mistakes being made or because of difficulties in marriage/relationship. CONCLUSIONS: Adults can feel guilty for a wide variety of different reasons. Most reasons seem to be rather concrete (e.g., related to concrete negative self-attributions/flaws or to concrete social situations with concrete individuals). There also seem to be some age- and gender-related differences in reasons for feeling guilty.

Loss and grief in elderly people: Results from the LIFE-Adult-Study.

We evaluated 2,865 elderly people to investigate the prevalence of prolonged grief disorder (PGD), examine predictors and mental health correlates. The conditional prevalence of PGD varied between 0.8% and 5.2% (diagnostic algorithm vs. cut-off). PG-13 scores were related to depressive symptoms, sleep disturbances, reduced life satisfaction, and quality of life. Predictors were female gender, less time since death, more losses, having lost a child, partner, or sibling, and less social support. PGD is associated with adverse mental health consequences. Practitioners should pay special attention to elderly women who lost a close loved one and lack social support.

Relationships Between Self-Rated Health at Three Time Points: Past, Present, Future.

Background: Multiple studies have shown that people who have experienced a serious health problem such as an injury tend to overrate the quality of health they had before that event. The main objective of this study was to test whether the phenomenon of respondents overrating their past health can also be observed in people from the general population. A second aim was to test whether habitual optimism is indeed focused on events in the future. Method: A representatively selected community sample from Leipzig, Germany (n = 2282, age range: 40-75 years) was examined. Respondents were asked to assess their current health, their past health (5 years before), and their expected future health (in 5 years) on a 0-100 scale. In addition, the study participants completed several questionnaires on specific aspects of physical and mental health. Results: Respondents of all age groups assessed their health as having been better in the past than it was at present. Moreover, they also assessed their earlier state of health more positively than people 5 years younger did their current state. Habitual optimism was associated with respondents having more positive expectations of how healthy they will be in 5 years time (r = 0.37), but the correlation with their assessments of their current health was nearly as high (r = 0.36). Conclusion: Highly positive scores of retrospectively assessed health among people who have experienced a health problem cannot totally be accounted for by a response to that health problem.

Reading cognition from the eyes: association of retinal nerve fibre layer thickness with cognitive performance in a population-based study.

With the eye as a window to the brain, non-invasive fast screening of retinal nerve fibre layer thickness poses the opportunity for early detection of cognitive decline leading to dementia. Our objective is to determine whether performance in various neurocognitive tests has an association with itemized retinal nerve fibre layer thickness. Detailed investigation of associations factored in sex and eye-side. The large population-based LIFE-Adult study (Leipzig Research Centre for Civilization Diseases) was conducted at Leipzig University, Germany from 2011 to 2014. Randomly selected participants (N = 10 000) were drawn from population registry in an age- and gender-stratified manner, focusing on 40-80 years. Cognitive function was examined with the CERAD-NP Plus test-battery (Consortium to Establish a Registry for Alzheimer's Disease), Stroop-Test, Reading the Mind in the Eyes-Test and Multiple-Choice Vocabulary Intelligence Test. Circumpapillary retinal nerve fibre layer thickness was measured with Optical Coherence Tomography. Subjects with reliable measurements (≥50 B-scan repetitions, signal-to-noise-ratio ≥20 dB, ≤5% missing A-scans) and without clinical eye pathology (sample A) and additional exclusion due to conditions of the central nervous system (sample B) were evaluated. The relationship between cognitive function and retinal nerve fibre layer thickness was investigated for six segments: temporal, temporal-superior, temporal-inferior, nasal, nasal-superior and nasal-inferior. For comparison with other studies, global mean is given. Brain-side projection analysis links results to the corresponding brain hemisphere. We analysed 11 124 eyes of 6471 subjects [55.5 years of age (19.1-79.8 years), 46.9% male]. Low cognitive performance was predominantly associated with thinner retinal nerve fibre layer thickness. Correlation analysis indicated emphasis on global and temporally located effects. Multivariable regression analysis with adjustments (age, sex and scan radius) presented individual results for each test, differentiating between sex and eye-side. For instance, verbal fluency tests and Trail Making Test-B show stronger association in females; Trail Making Test-A shows right-eye dominance. Findings in Trail-Making-Test-A projected to left brain hemisphere, and the ratio incongruent to neutral in the Stroop test projected to right brain-hemisphere. Separate assessment for sex and eye-side is presented for the first time in a population-based study. Location-specific sectorial retinal nerve fibre layer thickness was found to be an indicator for cognitive performance, giving an option for early detection of cognitive decline and the potential of early treatment. The eye as a window to the brain was studied with optical coherence tomography and connected to cognition. Girbardt et al. report that thinner retinal nerve fibre layer thickness was found to be a meaningful index for poorer cognitive performance which presents the potential for prediction of future cognitive decline.

[Lifetime Prevalence of Feelings of Guilt in the German Adult Population - Results of a Nation-Wide Telephone Survey]. / Die Lebenszeitprävalenz von Schuldgefühlen in der deutschen Erwachsenenbevölkerung ­ Ergebnisse einer bundesweiten telefonischen Bevölkerungsbefragung.

OBJECTIVE: To provide information on lifetime prevalence of feelings of guilt in the German adult population based on data from a nation-wide telephone survey (n = 1.003; 18+ years; May-June 2019). METHODS: We calculated weighted lifetime prevalence rates with confidence intervals (95 %-CI) and used multivariable logistic regression analyses to evaluate the association of guilt feelings with covariates. RESULTS: We identified a weighted lifetime prevalence of experienced feelings of guilt of 68.5 % (95 %-CI = 65.6-71.3). Younger age, higher education and current depressive symptoms were associated with higher prevalence rates. No association was found with regard to gender and major depression. CONCLUSION: A substantial part of the adult population experienced some sort of guilt feelings in their lives. Further research efforts are required to answer the question whether feelings of guilt are only a criterion of depression or whether they may contribute to an increased risk of the disorder.

Feelings of guilt in the general adult population: prevalence, intensity and association with depression.

To feel guilty can motivate for prosocial behavior but may also lead to negative health-related outcomes. The aim of this study was to provide epidemiological information on guilt feelings in the German general adult population. Based on findings from a nation-wide telephone survey (n=1,003 adultsaged 18+ years), we calculated weighted point prevalence rates for guilt feelings and used multivariable logistic regression analyses to evaluate the association between the guilt feelings and covariates. Prevalence of current guilt feelings was 10.6% (95%-CI=8.7-12.6). About one fourth of the adults with current guilt feelings rated the intensity of their feelings as 'rather strong' or 'very strong'. To feel guilty was unrelated to age, sex and education, but significantly associated with depression. The weighted prevalence of guilt feelings in adults with major depression was 37.4% (95%-CI=26.2-48.7) compared to 8.1% (95%-CI=6.4-9.9) in adults without. A substantial part of the German adult population is confronted with guilt feelings. Feeling guilty seems to be less dependent on rather global socio-demographic characteristics than on others factors like depression. More efforts have to be made to identify those specific circumstances, under which feelings of guilt lead to adverse health-related outcomes and to provide corresponding treatment approaches.

Mindreading From the Eyes Declines With Aging - Evidence From 1,603 Subjects.

Social cognition, in particular mindreading, enables the understanding of another individual's feelings, intentions, desires, and mental states. The Reading the Mind in the Eyes Test (RMET) captures the ability to identify mental states from gaze. We investigated RMET accuracy in the context of age and cognition across the whole adult age-range (19-79 years) in a very large population-based sample (N = 1,603) with linear regression models accounting for cognitive abilities, neurological diseases, and psychiatric disorders. Higher age predicted lower RMET performance in women and men, suggesting difficulties to infer mental states from gaze at older age. Effects remained stable when taking other cognitive abilities and psychiatric disorders or neurological diseases into account. Our results show that RMET performance as a measure of social cognition declines with increasing age.

Do High Mental Demands at Work Protect Cognitive Health in Old Age via Hippocampal Volume? Results From a Community Sample.

As higher mental demands at work are associated with lower dementia risk and a key symptom of dementia is hippocampal atrophy, the study aimed at investigating the association between mental demands at work and hippocampal volume. We analyzed data from the population-based LIFE-Adult-Study in Leipzig, Germany (n = 1,409, age 40-80). Hippocampal volumes were measured via three-dimensional Magnetic resonance imaging (MRI; 3D MP-RAGE) and mental demands at work were classified via the O*NET database. Linear regression analyses adjusted for gender, age, education, APOE e4-allele, hypertension, and diabetes revealed associations between higher demands in "language and knowledge," "information processing," and "creativity" at work on larger white and gray matter volume and better cognitive functioning with "creativity" having stronger effects for people not yet retired. Among retired individuals, higher demands in "pattern detection" were associated with larger white matter volume as well as larger hippocampal subfields CA2/CA3, suggesting a retention effect later in life. There were no other relevant associations with hippocampal volume. Our findings do not support the idea that mental demands at work protect cognitive health via hippocampal volume or brain volume. Further research may clarify through what mechanism mentally demanding activities influence specifically dementia pathology in the brain.

Correlates of hospitalization among the oldest old: results of the AgeCoDe-AgeQualiDe prospective cohort study.

BACKGROUND: Hospitalization is a key driver of health care costs. Thus far, there are only a few longitudinal studies investigating whether changes in explanatory variables lead to hospitalization. Moreover, these longitudinal studies did not focus on individuals in highest age. AIM: The purpose of the current study was to examine the correlates of hospitalization among the oldest old in Germany longitudinally. METHODS: A multicenter prospective cohort study ["Study on Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)", AgeQualiDe]. Primary care patients ≥ 85 years took part [n = 861 at follow-up (FU) 7, average age of 89.0 years; 85-100 years]. Two waves were used. Hospitalization in the last 6 months was used as outcome measure. Well-established scales were used to quantify the independent variables such as Instrumental Activities of Daily Living Scale, Global Deterioration Scale or Geriatric Depression Scale. RESULTS: Logistic random effects regressions showed that the probability of hospitalization in the preceding 6 months significantly increased with increases in the social network, more depressive symptoms, functional decline, and increase in chronic conditions, whereas it was not significantly associated with age, sex, marital status, education, and cognitive impairment. Social networks moderate the relationship between functional decline and hospitalization. DISCUSSION: The results of the present longitudinal study emphasize the association of depressive symptoms, functional decline, more social networks, and chronic conditions with hospitalization among the oldest old. CONCLUSIONS: Treatments with the aim to reduce or postpone these factors might also help to reduce hospitalization.

Determinants of incident dementia in different old age groups: results of the prospective AgeCoDe/AgeQualiDe study.

OBJECTIVES: To examine the impact of determinants of incident dementia in three different old age groups (75-79, 80-84, 85+years) in Germany. DESIGN: Multicenter prospective AgeCoDe/AgeQualiDe cohort study with baseline and nine follow-up assessments at 1.5-year intervals. SETTING: Primary care medical record registry sample. PARTICIPANTS: General practitioners' (GPs) patients aged 75+years at baseline. MEASUREMENTS: Conduction of standardized interviews including neuropsychological assessment and collection of GP information at each assessment wave. We used age-stratified competing risk regression models (accounting for the competing event of mortality) to assess determinants of incident dementia and age-stratified ordinary least square regressions to quantify the impact of identified determinants on the age at dementia onset. RESULTS: Among 3027 dementia-free GP patients, n = 704 (23.3%) developed dementia during the 13-year study period. Worse cognitive performance and subjective memory decline with related worries at baseline, and the APOE ε4 allele were associated independently with increased dementia risk in all three old age groups. Worse cognitive performance at baseline was also associated with younger age at dementia onset in all three age groups. Other well-known determinants were associated with dementia risk and age at dementia onset only in some or in none of the three old age groups. CONCLUSIONS: This study provides further evidence for the age-specific importance of determinants of incident dementia in old age. Such specifics have to be considered more strongly particularly with regard to potential approaches of early detection and prevention of dementia.

Alzheimer's disease-associated (hydroxy)methylomic changes in the brain and blood.

BACKGROUND: Late-onset Alzheimer's disease (AD) is a complex multifactorial affliction, the pathogenesis of which is thought to involve gene-environment interactions that might be captured in the epigenome. The present study investigated epigenome-wide patterns of DNA methylation (5-methylcytosine, 5mC) and hydroxymethylation (5-hydroxymethylcytosine, 5hmC), as well as the abundance of unmodified cytosine (UC), in relation to AD. RESULTS: We identified epigenetic differences in AD patients (n = 45) as compared to age-matched controls (n = 35) in the middle temporal gyrus, pertaining to genomic regions close to or overlapping with genes such as OXT (- 3.76% 5mC, pSidák = 1.07E-06), CHRNB1 (+ 1.46% 5hmC, pSidák = 4.01E-04), RHBDF2 (- 3.45% UC, pSidák = 4.85E-06), and C3 (- 1.20% UC, pSidák = 1.57E-03). In parallel, in an independent cohort, we compared the blood methylome of converters to AD dementia (n = 54) and non-converters (n = 42), at a preclinical stage. DNA methylation in the same region of the OXT promoter as found in the brain was found to be associated with subsequent conversion to AD dementia in the blood of elderly, non-demented individuals (+ 3.43% 5mC, pSidák = 7.14E-04). CONCLUSIONS: The implication of genome-wide significant differential methylation of OXT, encoding oxytocin, in two independent cohorts indicates it is a promising target for future studies on early biomarkers and novel therapeutic strategies in AD.