Subjective working and declarative memory in dementia and normal aging.

OBJECTIVE: Subjective memory complaints are common in both elderly individuals and patients with dementia. This study investigated the power of subjective memory, divided into declarative and working memory, to differentiate between patients with dementia and normal elderly individuals. METHOD: Two groups of participants, patients with dementia (n = 117) and normal elderly individuals (n = 117), individually matched with regard to age, gender, and education. All subjects had participated in the third wave of the HUNT population health survey in Nord-Trøndelag County in Norway and completed the Meta-Memory Questionnaire (MMQ) in the HUNT study. The MMQ was subdivided into two components, one associated with declarative memory (episodic and semantic) and the other with working memory. RESULTS: Patients with dementia reported significantly more subjective memory concerns than normal elderly individuals. The difference between working and declarative memory components was significantly greater in patients with dementia than in normal elderly individuals. This finding made it possible to differentiate patients with dementia from the normal elderly individuals. Mental and somatic health conditions did not significantly add power to differentiating the two groups. CONCLUSION: In clinical and research applications, subjective memory components could contribute to differentiation of patients with dementia and normal elderly individuals by using self-reported impairment in working memory, rather than declarative memory.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prevalence and Determinants of Diagnosed Dementia: A Registry Linkage Study Linking Diagnosis of Dementia in the Population-Based HUNT Study to Registry Diagnosis of Dementia in Primary Care and Hospitals in Norway.

Background: A timely diagnosis of dementia can be beneficial for providing good support, treatment, and care, but the diagnostic rate remains unknown and is probably low. Objective: To determine the dementia diagnostic rate and to describe factors associated with diagnosed dementia. Methods: This registry linkage study linked information on research-based study diagnoses of all-cause dementia and subtypes of dementias, Alzheimer's disease, and related dementias, in 1,525 participants from a cross-sectional population-based study (HUNT4 70+) to dementia registry diagnoses in both primary-care and hospital registries. Factors associated with dementia were analyzed with multiple logistic regression. Results: Among those with research-based dementia study diagnoses in HUNT4 70+, 35.6% had a dementia registry diagnosis in the health registries. The diagnostic rate in registry diagnoses was 19.8% among home-dwellers and 66.0% among nursing home residents. Of those with a study diagnosis of Alzheimer's disease, 35.8% (95% confidence interval (CI) 32.6-39.0) had a registry diagnosis; for those with a study diagnosis of vascular dementia, the rate was 25.8% (95% CI 19.2-33.3) and for Lewy body dementias and frontotemporal dementia, the diagnosis rate was 63.0% (95% CI 48.7-75.7) and 60.0% (95% CI 43.3-75.1), respectively. Factors associated with having a registry diagnosis included dementia in the family, not being in the youngest or oldest age group, higher education, more severe cognitive decline, and greater need for help with activities of daily living. Conclusions: Undiagnosed dementia is common, as only one-third of those with dementia are diagnosed. Diagnoses appear to be made at a late stage of dementia.

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.

Temporal changes in personal activity intelligence and the risk of incident dementia and dementia related mortality: A prospective cohort study (HUNT).

Background: The Personal Activity Intelligence (PAI) translates heart rate during daily activity into a weekly score. Obtaining a weekly PAI score ≥100 is associated with reduced risk of premature morbidity and mortality from cardiovascular diseases. Here, we determined whether changes in PAI score are associated with changes in risk of incident dementia and dementia-related mortality. Methods: We conducted a prospective cohort study of 29,826 healthy individuals. Using data from the Trøndelag Health-Study (HUNT), PAI was estimated 10 years apart (HUNT1 1984-86 and HUNT2 1995-97). Adjusted hazard-ratios (aHR) and 95%-confidence intervals (CI) for incidence of and death from dementia were related to changes in PAI using Cox regression analyses. Findings: During a median follow-up time of 24.5 years (interquartile range [IQR]: 24.1-25.0) for dementia incidence and 23.6 years (IQR: 20.8-24.2) for dementia-related mortality, there were 1998 incident cases and 1033 dementia-related deaths. Individuals who increased their PAI score over time or maintained a high PAI score at both assessments had reduced risk of dementia incidence and dementia-related mortality. Compared with persistently inactive individuals (0 weekly PAI) at both time points, the aHRs for those with a PAI score ≥100 at both occasions were 0.75 (95% CI: 0.58-0.97) for incident dementia, and 0.62 (95% CI: 0.43-0.91) for dementia-related mortality. Using PAI score <100 at both assessments as the reference cohort, those who increased from <100 at HUNT1 to ≥100 at HUNT2 had aHR of 0.83 (95% CI: 0.72-0.96) for incident dementia, and gained 2.8 (95% CI: 1.3-4.2, P<0.0001) dementia-free years. For dementia-related mortality, the corresponding aHR was 0.74 (95% CI: 0.59-0.92) and years of life gained were 2.4 (95% CI: 1.0-3.8, P=0.001). Interpretation: Maintaining a high weekly PAI score and increases in PAI scores over time were associated with a reduced risk of incident dementia and dementia-related mortality. Our findings extend the scientific evidence regarding the protective role of PA for dementia prevention, and suggest that PAI may be a valuable tool in guiding research-based PA recommendations. Funding: The Norwegian Research Council, the Liaison Committee between the Central Norway Regional Health Authority and Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease.

Late-onset Alzheimer's disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer's disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer's disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer's disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer's disease to identify further genetic variants that contribute to Alzheimer's pathology.

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.

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.

Temporal changes in cardiorespiratory fitness and risk of dementia incidence and mortality: a population-based prospective cohort study.

BACKGROUND: Cardiorespiratory fitness is associated with risk of dementia, but whether temporal changes in cardiorespiratory fitness influence the risk of dementia incidence and mortality is still unknown. We aimed to study whether change in estimated cardiorespiratory fitness over time is associated with change in risk of incident dementia, dementia-related mortality, time of onset dementia, and longevity after diagnosis in healthy men and women at baseline. METHODS: We linked data from the prospective Nord-Trøndelag Health Study (HUNT) done in Nord-Trøndelag, Norway with dementia data from the Health and Memory Study and cause of death registries (n=30 375). Included participants were apparently healthy individuals for whom data were available on estimated cardiorespiratory fitness and important confounding factors. Datasets were matched to each participant through their 11-digit personal identification number. Cardiorespiratory fitness was estimated on two occasions 10 years apart, during HUNT1 (1984-86) and HUNT2 (1995-97). HUNT2 was used as the baseline for follow-up. Participants were classified into two sex-specific estimated cardiorespiratory fitness groups according to their age (10-year categories): unfit (least fit 20% of participants) and fit (most fit 80% of participants). To assess the association between change in estimated cardiorespiratory fitness and dementia, we used four categories of change: unfit at both HUNT1 and HUNT2, unfit at HUNT1 and fit at HUNT2, fit at HUNT1 and unfit at HUNT2, fit at both HUNT1 and HUNT2. Using Cox proportional hazard analyses, we estimated adjusted hazard ratios (AHR) for dementia incidence and mortality related to temporal changes in estimated cardiorespiratory fitness. FINDINGS: During a median follow-up of 19·6 years for mortality, and 7·6 years for incidence, there were 814 dementia-related deaths, and 320 incident dementia cases. Compared with participants who were unfit at both assessments, participants who sustained high estimated cardiorespiratory fitness had a reduced risk of incident dementia (AHR 0·60, 95% CI 0·36-0·99) and a reduced risk of dementia mortality (0·56, 0·43-0·75). Participants who had an increased estimated cardiorespiratory fitness over time had a reduced risk of incident dementia (AHR 0·52, 95% CI 0·30-0·90) and dementia mortality (0·72, 0·52-0·99) when compared with those who remained unfit at both assessments. Each metabolic equivalent of task increase in estimated cardiorespiratory fitness was associated with a risk reduction of incident dementia (adjusted HR 0·84, 95% CI 0·75-0·93) and dementia mortality (0·90, 0·84-0·97). Participants who increased their estimated cardiorespiratory fitness over time gained 2·2 (95% CI 1·0-3·5) dementia-free years, and 2·7 (0·4-5·8) years of life when compared with those who remained unfit at both assessments. INTERPRETATION: Change in estimated cardiorespiratory fitness is an independent risk factor for incidence dementia and dementia mortality. Maintaining or improving cardiorespiratory fitness over time may be a target to reduce risk of dementia incidence and mortality, delay onset, and increase longevity after diagnosis. Our data highlight the importance of assessing cardiorespiratory fitness in health risk assessment for people at risk of dementia. FUNDING: The KG Jebsen Foundation, the Norwegian Research Council, the Liaison Committee between the Central Norway Regional Health Authority, and the Norwegian University of Science and Technology.

Selective impact of disease on short-term and long-term components of self-reported memory: a population-based HUNT study.

BACKGROUND: Subjective memory is commonly considered to be a unidimensional measure. However, theories of performance-based memory suggest that subjective memory could be divided into more than one dimension. OBJECTIVE: To divide subjective memory into theoretically related components of memory and explore the relationship to disease. METHODS: In this study, various aspects of self-reported memory were studied with respect to demographics and diseases in the third wave of the HUNT epidemiological study in middle Norway. The study included all individuals 55 years of age or older, who responded to a nine-item questionnaire on subjective memory and questionnaires on health (n=18 633). RESULTS: A principle component analysis of the memory items resulted in two memory components; the criterion used was an eigenvalue above 1, which accounted for 54% of the total variance. The components were interpreted as long-term memory (LTM; the first component; 43% of the total variance) and short-term memory (STM; the second component; 11% of the total variance). Memory impairment was significantly related to all diseases (except Bechterew's disease), most strongly to brain infarction, heart failure, diabetes, cancer, chronic obstructive pulmonary disease and whiplash. For most diseases, the STM component was more affected than the LTM component; however, in cancer, the opposite pattern was seen. CONCLUSIONS: Subjective memory impairment as measured in HUNT contained two components, which were differentially associated with diseases.