Subjective working memory predicts objective memory in cognitively normal aging: a HUNT study

Background Recent studies have shown that subjective memory is multi-, rather than uni-dimensional, in line with the results of objective memory tests. The purpose of this study was to investigate whether there is an association between aspects of memory measured by the subjective Meta-Memory Questionnaire (MMQ) and aspects of memory measured by the objective Wechsler Memory Scale-III (WMS-III) and Wechsler Adult Intelligence Scale-III (WAIS-III) tests in cognitively normal older adults. Method The study subjects (n = 106) were cognitively normal, were aged 57–89 years and had participated in the third wave of the North-Trøndelag Health survey (HUNT3). All subjects had completed the MMQ, the WMS-III and the WAIS-III. Previous results from the MMQ (measured as the total MMQ score; the Component I score, related to long-term explicit declarative memory; and the Component II score, related to working/short-term memory) were compared with objective results from WMS-III (Logical Memory) and WAIS-III (Vocabulary and Letter-Number Sequencing) subtests. We conducted linear regression analyses with each objective memory test result as the dependent variable, and subjective memory measures and demographics as independent variables, as well as analyses of MMQ items vs. objective memory. Results Subjective working memory impairment (Component II) was significant related to poor performance in objective episodic memory, according to correlation and regression analyses with demographic covariates. In contrast, ratings of impaired subjective declarative memory (Component I) were not related to poor objective memory performance. Conclusions Specific aspects of subjective memory related differentially to performance in specific objective memory tests. Clinicians and researchers might consider targeting working memory aspects of subjective memory tests, when seeking an estimate of objective memory performance.publishedVersio

Successfully aging elderly (SAE): A short overview of some important aspects of successful aging

Whether one falls into the category of successfully aging elderly (SAE) is generally determined by biological, medical, psychological, and cognitive factors. SAE, pathological aging and usual aging, are the three subgroups presented in the seminal science paper by Rowe & Kahn in 1987. SAE is currently vaguely defined as being free of disease, having preserved cognitive function and an active life, but a more detailed definition is lacking. As a result, the research on SAE is heterogeneous and hard to summarize. Nevertheless, it is clear that genetics, health, basic aging mechanisms, brain changes, cognition early in life, education level, lifestyle factors, subjective factors, the availability of societal health care, environmental factors, and any interaction between all these variables, are important. There are also methodological difficulties associated with studies of causal relationships across the lifespan. Obtaining a detailed understanding of SAE research will be a challenging task for future researchers.publishedVersionThe Norwegian Journal of Epidemiology is open access, and can be downloaded freely from this website

Processing speed and working memory are predicted by components of successful aging: a HUNT study

Background Research has demonstrated that cognitive heterogeneity occurs with aging both within and between individuals. The purpose of this study was to explore whether the cognitive heterogeneity in aging was related to the subgroups of successful and usual aging. Method Participants were a representative sample of normal older adults (n = 65, age range 70–89 years). All subjects had participated in the third phase of the Nord-Trøndelag Health Survey (HUNT3) and completed all subtests in the Wechsler Memory Scale (WMS-III) and Wechsler Adult Intelligence Scale (WAIS-III). Successful aging was defined in four ways in the study: as (1) absence of disease, (2) high functioning, (3) active engagement with life, or (4) all three components combined. Five domains of memory and intelligence functions were investigated using linear regression analysis, with group membership (successful versus usual aging) as predictors and age, sex and education as correlates. Results Processing speed performance was correlated with the successful aging component absence of disease, younger age and being of the female sex, while working memory performance was correlated with the successful aging component absence of disease and more years of education. Performance in other domains (verbal, visuospatial, and episodic memory) were not related to any successful aging definition. Age had a consistent negative effect on the processing speed domain for all successful aging definitions. Education was positively linked to cognitive performance on the verbal and working memory domains. Being female was positively linked to processing speed and episodic memory. Conclusions Processing speed and working memory were linked to successful aging when it was defined as absence of disease, but not by other components of successful aging, i.e. domain-specific. In contrast, other cognitive domains were not related to any components of successful aging.publishedVersio

Lifestyle predictors of successful aging: A 20-year prospective HUNT study

Background Lifestyle factors predicting successful aging as a unified concept or as separate components of successful aging are important for understanding healthy aging, interventions and preventions. The main objective was to investigate the effect of midlife predictors on subsequent successful aging 20 years later. Materials and methods Data were from a population-based health survey, the Nord-Trøndelag Health Study (HUNT), with an average follow-up of 22.6 years. Individuals free of major disease at baseline in 1984–86 with complete datasets for the successful aging components in HUNT3 in 2006–08, were included (n = 4497; mean age at baseline 52.7, range 45–59, years). Successful aging was defined either as a unified category or as three components: being free of nine specified diseases and depression, having no physical or cognitive impairment, and being actively engaged with life. The midlife predictors (smoking, physical activity, alcohol consumption, obesity and social support) were analysed both as separate predictors and combined into a lifestyle index controlling for sociodemographic variables, using multivariable regression analysis. Results Successful aging as a unified concept was related to all the lifestyle factors in the unadjusted analyses, and all except alcohol consumption in the adjusted analyses. The individual components of successful aging were differently associated with the lifestyle factors; engagement with life was less associated with the lifestyle factors. Non- smoking and good social support were the most powerful predictors for successful aging as a unified concept. When the lifestyle factors were summed into a lifestyle index, there was a trend for more positive lifestyle to be related to higher odds for successful aging. Conclusions Lifestyle factors predicted an overall measure of SA, as well as the individual components, more than 20 years later. Modifiable risk factors in midlife, exemplified by social support, may be used for interventions to promote overall health and specific aspects of health in aging.publishedVersion© 2019 Bosnes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Prevalence and correlates of successful aging in a population-based sample of older adults: The HUNT study

The factors influencing successful aging (SA) are of great interest in an aging society. The aims of this study were to investigate the prevalence of SA, the relative importance across age of the three components used to define it (absence of disease and disability, high cognitive and physical function, and active engagement with life), and its correlates. Data were extracted from the population-based cross-sectional Nord-Trøndelag Health Study (HUNT3 2006–2008). Individuals aged 70–89 years with complete datasets for the three components were included (N = 5773 of 8,040, 71.8%). Of the respondents, 54.6% were women. Univariate and multivariate regression analyses were used to analyze possible correlates of SA. Overall, 35.6% of the sample met one of the three criteria, 34.1% met combinations, and 14.5% met all of the three criteria. The most demanding criterion was high function, closely followed by absence of disease, while approximately two-thirds were actively engaged in life. The relative change with age was largest for the high cognitive and physical function component and smallest for active engagement with life. The significant correlates of SA were younger age, female gender, higher education, weekly exercise, more satisfaction with life, non-smoking, and alcohol consumption, whereas marital status was not related to SA. The prevalence of SA in this study (14.5%) is comparable to previous studies. It may be possible to increase the prevalence by intervention directed toward more exercise, non-smoking, and better satisfaction with life.acceptedVersion© 2017. This is the authors' accepted and refereed manuscript to the article. The final authenticated version is available online at: https://doi.org/10.1017/S104161021600186

Anxiety and Depression as Risk Factors in Frontotemporal Dementia and Alzheimer’s Disease: The HUNT Study

Background: The roles of both anxiety and depression as risk factors for frontotemporal dementia (FTD) and Alzheimer’s disease (AD) have not been previously investigated together. Objective: To study anxiety and depression as independent risk factors for FTD and AD. Methods: Eighty-four patients with FTD and 556 patients with AD were compared with 117 cognitively healthy (CH), elderly individuals. Both cases and controls were participants in the second Health Study of Nord-Trøndelag (HUNT2) from 1995 to 1997, in which depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS). Results: Significant associations were found between anxiety and FTD and between depression and AD. A significantly increased risk of developing FTD was observed in patients who had reported anxiety on the HADS (p = 0.017) (odds ratio [OR]: 2.947, 95% confidence interval [CI]: 1.209–7.158) and a significantly increased risk of developing AD was observed in patients who had reported depression on the HADS (p = 0.016) (OR: 4.389, 95% CI: 1.311–14.690). Conclusion: Our study findings suggest that anxiety and depression may play different roles as risk factors for FTD and AD

A genome-wide association meta-analysis of all-cause and vascular dementia

INTRODUCTION Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD. METHODS We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors. RESULTS For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability (ANO3), amyloid deposition in the brain (RBFOX1), and magnetic resonance imaging markers of small vessel disease (SVD; HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, and PSMA3). DISCUSSION Our study identified genetic risks underlying ACD, demonstrating overlap with neurodegenerative processes, vascular risk factors, and cerebral SVD. Highlights We conducted the largest genome-wide association study of all-cause dementia (ACD) and vascular dementia (VaD). Known genetic variants associated with AD were replicated for ACD and VaD. Functional analyses identified novel loci for ACD and VaD. Genetic risks of ACD overlapped with neurodegeneration, vascular risk factors, and cerebral small vessel disease.publishedVersio

A genome‐wide association meta‐analysis of all‐cause and vascular dementia

INTRODUCTION: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD. METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors. RESULTS: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability (ANO3), amyloid deposition in the brain (RBFOX1), and magnetic resonance imaging markers of small vessel disease (SVD; HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, and PSMA3). DISCUSSION: Our study identified genetic risks underlying ACD, demonstrating overlap with neurodegenerative processes, vascular risk factors, and cerebral SVD. Highlights: We conducted the largest genome-wide association study of all-cause dementia (ACD) and vascular dementia (VaD). Known genetic variants associated with AD were replicated for ACD and VaD. Functional analyses identified novel loci for ACD and VaD. Genetic risks of ACD overlapped with neurodegeneration, vascular risk factors, and cerebral small vessel disease

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues