Eicosapentaenoic Acid Is Associated with Decreased Incidence of Alzheimer’s Dementia in the Oldest Old

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

Do self-reported hearing and visual impairments predict longitudinal dementia in older adults?

Background Sensory impairments have been associated with dementia in older adults. However, the contribution of different impairments and how they interact in the development of dementia is not clear. We examined the independent and interaction effects of hearing impairment (HI) and visual impairment (VI) on incident dementia. Design Multi-centric population-based prospective cohort study. Setting Data were taken from the AgeDifferent.de platform, pooling participants aged 75 and older from the German LEILA75+ and AgeCoDe/AgeQualiDe cohorts. Participants Older adults (N = 3497) with mean age 79.8 years, 67.2% female. Measurements Standardized interviews and questionnaires were used to assess self-reported HI and VI at baseline and all-cause dementia in 9 follow-ups, spanning over 20 years. Methods Competing risk regression models were conducted to test the main and interaction effects of HI and VI on dementia incidence, adjusting for established risk factors of dementia and accumulated mortality. Results HI and VI at baseline were reported by 30.3% and 16.6% of individuals, respectively. Adjusting for baseline information on sociodemographics, substance use, cognitive functioning and morbidity, and controlling for accumulated mortality risk, HI (sHR 1.16, 95% CI 1.04–1.30, p = 0.011) but not VI (sHR 1.07, 95% CI 0.90–1.28, p = 0.462) was significantly associated with incident dementia. There was no interaction between HI and VI (sHR 1.09, 95% CI 0.81–1.46, p = 0.567). Conclusions Hearing impairment is associated with an increased incidence of all-cause dementia in older adults. There is no excess risk or risk compensation through the additional presence or absence of visual impairment. Early prevention measures for hearing impairment might help to reduce the long-term risk of dementia

The importance of engaging in physical activity in older adulthood for transitions between cognitive status categories and death: A coordinated analysis of 14 longitudinal studies

Background: Given increasing incidence of cognitive impairment and dementia, further understanding of modifiable factors contributing to increased healthspan is crucial. Extensive literature provides evidence that physical activity (PA) delays the onset of cognitive impairment; however, it is unclear whether engaging in PA in older adulthood is sufficient to influence progression through cognitive status categories. Method: Applying a coordinated analysis approach, this project independently analyzed 14 longitudinal studies (NTotal = 52 039; mean baseline age across studies = 69.9-81.73) from North America and Europe using multistate survival models to estimate the impact of engaging in PA on cognitive status transitions (nonimpaired, mildly impaired, severely impaired) and death. Multinomial regression models were fit to estimate life expectancy (LE) based on American PA recommendations. Meta-analyses provided the pooled effect sizes for the role of PA on each transition and estimated LEs. Results: Controlling for baseline age, sex, education, and chronic conditions, analyses revealed that more PA is significantly associated with decreased risk of transitioning from nonimpaired to mildly impaired cognitive functioning and death, as well as substantially longer LE. Results also provided evidence for a protective effect of PA after onset of cognitive impairment (eg, decreased risk of transitioning from mild-to-severe cognitive impairment; increased likelihood of transitioning backward from severe-to-mild cognitive impairment), though between-study heterogeneity suggests a less robust association. Conclusions: These results yield evidence for the importance of engaging in PA in older adulthood for cognitive health, and a rationale for motivating older adults to engage consistently in PA

Changes in Social Network Size Are Associated With Cognitive Changes in the Oldest-Old

Objectives:Social isolation is increasing in aging societies and several studies have shown a relation with worse cognition in old age. However, less is known about the association in the oldest-old (85+); the group that is at highest risk for both social isolation and dementia. Methods:Analyses were based on follow-up 5 to 9 of the longitudinal German study on aging, cognition, and dementia in primary care patients (AgeCoDe) and the study on needs, health service use, costs, and health-related quality of life in a large sample of oldest-old primary care patients (AgeQualiDe), a multi-center population-based prospective cohort study. Measurements included the Lubben Social Network Scale (LSNS-6), with a score below 12 indicating social isolation, as well as the Mini-Mental Status Examination (MMSE) as an indicator of cognitive function. Results:Dementia-free study participants (n = 942) were M = 86.4 (SD = 3.0) years old at observation onset, 68.2% were women. One third (32.3%) of them were socially isolated. Adjusted linear hybrid mixed effects models revealed significantly lower cognitive function in individuals with smaller social networks (β = 0.5, 95% CI = 0.3-0.7, p < .001). Moreover, changes in an individual's social network size were significantly associated with cognitive changes over time (β = 0.2, 95% CI = 0.1-0.4, p = .003), indicating worse cognitive function with shrinking social networks. Conclusion:Social isolation is highly prevalent among oldest-old individuals, being a risk factor for decreases in cognitive function. Consequently, it is important to maintain a socially active lifestyle into very old age. Likewise, this calls for effective ways to prevent social isolation

The Role of Social Isolation and the Development of Depression: A Comparison of the Widowed and Married Oldest Old in Germany

Widowhood is common in old age, can be accompanied by serious health consequences and is often linked to substantial changes in social network. Little is known about the impact of social isolation on the development of depressive symptoms over time taking widowhood into account. We provide results from the follow-up 5 to follow-up 9 from the longitudinal study AgeCoDe and its follow-up study AgeQualiDe. Depression was measured with GDS-15 and social isolation was assessed using the Lubben Social Network Scale (LSNS-6). The group was aligned of married and widowed people in old age and education through entropy balancing. Linear mixed models were used to examine the frequency of occurrence of depressive symptoms for widowed and married elderly people depending on the risk of social isolation. Our study shows that widowhood alone does not lead to an increased occurrence of depressive symptoms. However, "widowed oldest old", who are also at risk of social isolation, have significantly more depressive symptoms than those without risk. In the group of "married oldest old", women have significantly more depressive symptoms than men, but isolated and non-isolated do not differ. Especially for people who have lost a spouse, the social network changes significantly and increases the risk for social isolation. This represents a risk factor for the occurrence of depressive symptoms

Friends and Foes from an Ant Brain's Point of View – Neuronal Correlates of Colony Odors in a Social Insect

Background: Successful cooperation depends on reliable identification of friends and foes. Social insects discriminate colony members (nestmates/friends) from foreign workers (non-nestmates/foes) by colony-specific, multi-component colony odors. Traditionally, complex processing in the brain has been regarded as crucial for colony recognition. Odor information is represented as spatial patterns of activity and processed in the primary olfactory neuropile, the antennal lobe (AL) of insects, which is analogous to the vertebrate olfactory bulb. Correlative evidence indicates that the spatial activity patterns reflect odor-quality, i.e., how an odor is perceived. For colony odors, alternatively, a sensory filter in the peripheral nervous system was suggested, causing specific anosmia to nestmate colony odors. Here, we investigate neuronal correlates of colony odors in the brain of a social insect to directly test whether they are anosmic to nestmate colony odors and whether spatial activity patterns in the AL can predict how odor qualities like ‘‘friend’’ and ‘‘foe’’ are attributed to colony odors. Methodology/Principal Findings: Using ant dummies that mimic natural conditions, we presented colony odors and investigated their neuronal representation in the ant Camponotus floridanus. Nestmate and non-nestmate colony odors elicited neuronal activity: In the periphery, we recorded sensory responses of olfactory receptor neurons (electroantennography), and in the brain, we measured colony odor specific spatial activity patterns in the AL (calcium imaging). Surprisingly, upon repeated stimulation with the same colony odor, spatial activity patterns were variable, and as variable as activity patterns elicited by different colony odors. Conclusions: Ants are not anosmic to nestmate colony odors. However, spatial activity patterns in the AL alone do not provide sufficient information for colony odor discrimination and this finding challenges the current notion of how odor quality is coded. Our result illustrates the enormous challenge for the nervous system to classify multi-component odors and indicates that other neuronal parameters, e.g., precise timing of neuronal activity, are likely necessary for attribution of odor quality to multi-component odors

Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: a cross-sectional study

Background: White matter hyperintensities (WMH) in subjects across the Alzheimer’s disease (AD) spectrum with minimal vascular pathology suggests that amyloid pathology—not just arterial hypertension—impacts WMH, which in turn adversely influences cognition. Here we seek to determine the effect of both hypertension and Aβ positivity on WMH, and their impact on cognition. Methods: We analysed data from subjects with a low vascular profile and normal cognition (NC), subjective cognitive decline (SCD), and amnestic mild cognitive impairment (MCI) enrolled in the ongoing observational multicentre DZNE Longitudinal Cognitive Impairment and Dementia Study (n = 375, median age 70.0 [IQR 66.0, 74.4] years; 178 female; NC/SCD/MCI 127/162/86). All subjects underwent a rich neuropsychological assessment. We focused on baseline memory and executive function—derived from multiple neuropsychological tests using confirmatory factor analysis—, baseline preclinical Alzheimer’s cognitive composite 5 (PACC5) scores, and changes in PACC5 scores over the course of three years (ΔPACC5). Results: Subjects with hypertension or Aβ positivity presented the largest WMH volumes (pFDR < 0.05), with spatial overlap in the frontal (hypertension: 0.42 ± 0.17; Aβ: 0.46 ± 0.18), occipital (hypertension: 0.50 ± 0.16; Aβ: 0.50 ± 0.16), parietal lobes (hypertension: 0.57 ± 0.18; Aβ: 0.56 ± 0.20), corona radiata (hypertension: 0.45 ± 0.17; Aβ: 0.40 ± 0.13), optic radiation (hypertension: 0.39 ± 0.18; Aβ: 0.74 ± 0.19), and splenium of the corpus callosum (hypertension: 0.36 ± 0.12; Aβ: 0.28 ± 0.12). Elevated global and regional WMH volumes coincided with worse cognitive performance at baseline and over 3 years (pFDR < 0.05). Aβ positivity was negatively associated with cognitive performance (direct effect—memory: − 0.33 ± 0.08, pFDR < 0.001; executive: − 0.21 ± 0.08, pFDR < 0.001; PACC5: − 0.29 ± 0.09, pFDR = 0.006; ΔPACC5: − 0.34 ± 0.04, pFDR < 0.05). Splenial WMH mediated the relationship between hypertension and cognitive performance (indirect-only effect—memory: − 0.05 ± 0.02, pFDR = 0.029; executive: − 0.04 ± 0.02, pFDR = 0.067; PACC5: − 0.05 ± 0.02, pFDR = 0.030; ΔPACC5: − 0.09 ± 0.03, pFDR = 0.043) and WMH in the optic radiation partially mediated that between Aβ positivity and memory (indirect effect—memory: − 0.05 ± 0.02, pFDR = 0.029). Conclusions: Posterior white matter is susceptible to hypertension and Aβ accumulation. Posterior WMH mediate the association between these pathologies and cognitive dysfunction, making them a promising target to tackle the downstream damage related to the potentially interacting and potentiating effects of the two pathologies. Trial registration: German Clinical Trials Register (DRKS00007966, 04/05/2015)