'Do you have a future when you are 93?' Frail older person's perceptions about the future and end of life - a qualitative interview study in primary care.

OBJECTIVE: To explore frail older persons' perceptions of the future and the end of life. DESIGN: Qualitative content analysis of individual semi-structured interviews. SETTING: Nine primary health care centres in both small and middle-sized municipalities in Sweden that participated in the intervention project Proactive healthcare for frail elderly persons. SUBJECTS/PATIENTS: The study includes 20 older persons (eight women and 12 men, aged 76-93 years). MAIN OUTCOME MEASURES: Frail older persons' perceptions of the future and end of life. RESULTS: The analysis uncovered two main categories: Dealing with the future and Approaching the end of life. Dealing with the future includes two subcategories: Plans and reflections and Distrust and delay. Approaching the end of life includes three subcategories: Practical issues, Worries and realism, and Keeping it away. CONCLUSION: This study highlights the diverse ways older people perceive future and the end of life. The results make it possible to further understand the complex phenomenon of frail older persons' perceptions on the future and the end of life.KEY POINTSThe study found that older persons described their future as contradictory- with a broad spectrum of approaches, where some wanted to deal with these subjects and others wanted to ignore them.•Older persons that consciously planned for the future had tactics that often were related to goals that functioned as motivators to live longer.•Those who adopted a more passive approach did not think about what the future might hold in terms of losing autonomy and deteriorating health.•Older persons that approached end of life in a more proactive way wanted to plan practical arrangements around death but often found it hard to address this issue with relatives.•Those older persons that had a more passive approach to end of life preferred not to think about those issues, and some explicitly stated that they did not want to address the final period of life.

Costs and effects of comprehensive geriatric assessment in primary care for older adults with high risk for hospitalisation.

BACKGROUND: The healthcare system needs effective strategies to identify the most vulnerable group of older patients, assess their needs and plan their care proactively. To evaluate the effectiveness of comprehensive geriatric assessment (CGA) of older adults with a high risk of hospitalisation we conducted a prospective, pragmatic, matched-control multicentre trial at 19 primary care practices in Sweden. METHODS: We identified 1604 individuals aged 75 years and older using a new, validated algorithm that calculates a risk score for hospitalisation from electronic medical records. After a nine-month run-in period for CGA in the intervention group, 74% of the available 646 participants had accepted and received CGA, and 662 participants remained in the control group. Participants at intervention practices were invited to CGA performed by a nurse together with a physician. The CGA was adapted to the primary care context. The participants thereafter received actions according to individual needs during a two-year follow-up period. Participants at control practices received care as usual. The primary outcome was hospital care days. Secondary outcomes were number of hospital care episodes, number of outpatient visits, health care costs and mortality. Outcomes were analysed according to intention to treat and adjusted for age, gender and risk score. We used generalised linear mixed models to compare the intervention group and control group regarding all outcomes. RESULTS: Mean age was 83.2 years, 51% of the 1308 participants were female. Relative risk reduction for hospital care days was - 22% (- 35% to - 4%, p = 0.02) during the two-year follow-up. Relative risk reduction for hospital care episodes was - 17% (- 30% to - 2%, p = 0.03). There were no significant differences in outpatient visits or mortality. Health care costs were significantly lower in the intervention group, adjusted mean difference was € - 4324 (€ - 7962 to - 686, p = 0.02). CONCLUSIONS AND RELEVANCE: Our findings indicate that CGA in primary care can reduce the need for hospital care days in a high-risk population of older adults. This could be of great importance in order to manage increasing prevalence of frailty and multimorbidity. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03180606 , first posted 08/06/2017.

Clinically useful prediction of hospital admissions in an older population.

BACKGROUND: The healthcare for older adults is insufficient in many countries, not designed to meet their needs and is often described as disorganized and reactive. Prediction of older persons at risk of admission to hospital may be one important way for the future healthcare system to act proactively when meeting increasing needs for care. Therefore, we wanted to develop and test a clinically useful model for predicting hospital admissions of older persons based on routine healthcare data. METHODS: We used the healthcare data on 40,728 persons, 75-109 years of age to predict hospital in-ward care in a prospective cohort. Multivariable logistic regression was used to identify significant factors predictive of unplanned hospital admission. Model fitting was accomplished using forward selection. The accuracy of the prediction model was expressed as area under the receiver operating characteristic (ROC) curve, AUC. RESULTS: The prediction model consisting of 38 variables exhibited a good discriminative accuracy for unplanned hospital admissions over the following 12 months (AUC 0.69 [95% confidence interval, CI 0.68-0.70]) and was validated on external datasets. Clinically relevant proportions of predicted cases of 40 or 45% resulted in sensitivities of 62 and 66%, respectively. The corresponding positive predicted values (PPV) was 31 and 29%, respectively. CONCLUSION: A prediction model based on routine administrative healthcare data from older persons can be used to find patients at risk of admission to hospital. Identifying the risk population can enable proactive intervention for older patients with as-yet unknown needs for healthcare.

Staff experiences of a new tool for comprehensive geriatric assessment in primary care (PASTEL): a focus group study.

Objective: Comprehensive geriatric assessment (CGA) is recommended for the management of frailty. Little is known about professionals' experiences of CGA; therefore we wanted to investigate the experiences of staff in primary care using a new CGA tool: the Primary care Assessment Tool for Elderly (PASTEL).Design: Focus group interviews. Manifest qualitative content analysis.Setting: Nine primary health care centres in Sweden that participated in a CGA intervention. These centres represent urban as well as rural areas.Subjects: Nine nurses, five GPs and one pharmacist were divided into three focus groups.Main outcome measures: Participants' experiences of conducting CGA with PASTEL.Results: The analysis resulted in four main categories. A valuable tool for selected patients: The participants considered the assessment tool to be feasible and valuable. They stated that having enough time for the assessment interview was essential but views about the ideal patient for assessment were divided. Creating conditions for dialogue: The process of adapting the assessment to the individual and create conditions for dialogue was recognised as important. Managing in-depth conversations: In-depth conversations turned out to be an important component of the assessment. Patients were eager to share their stories, but talking about the future or the end of life was demanding. The winding road of actions and teamwork: PASTEL was regarded as a good preparation tool for care planning and a means of support for identifying appropriate actions to manage frailty but there were challenges to implement these actions and to obtain good teamwork.Conclusion: The participants reported that PASTEL, a tool for CGA, gave a holistic picture of the older person and was helpful in care planning.Key pointsTo manage frailty using comprehensive geriatric assessment (CGA) in primary care, there is a need for tools that are efficient, user-friendly and which support patient involvement and teamwork•This study found that the Primary care Assessment tool for Elderly (PASTEL) is regarded as both valuable and feasible by primary care professionals•Use of carefully selected items in the tool and allowing enough time for dialogue may enhance patient-centeredness•The PASTEL tool supports the process of identifying actions to manage frailty in older adults. Teamwork related to the tool and CGA in primary care needs to be further investigated and developed.

Diagnostic Failure of Cognitive Impairment in Nursing Home Residents May Lead to Impaired Medical Care.

BACKGROUND/OBJECTIVES: Dementia and cognitive impairment are common in nursing homes. Few studies have studied the impact of unnoted cognitive impairment on medical care. This study aimed to estimate the prevalence of diagnostic failure of cognitive impairment in a sample of Swedish nursing home residents and to analyze whether diagnostic failure was associated with impaired medical care. METHOD: A total of 428 nursing home residents were investigated during 2008-2011. Subjects without dementia diagnosis were grouped by result of the Mini Mental State Examination (MMSE), where subjects with <24 points formed a possible dementia group and the remaining subjects a control group. A third group consisted of subjects with diagnosed dementia. These three groups were compared according to baseline data, laboratory findings, drug use, and mortality. RESULTS: Dementia was previously diagnosed in 181 subjects (42%). Among subjects without a dementia diagnosis, 72% were cognitively impaired with possible dementia (MMSE <24). These subjects were significantly older, did not get anti-dementia treatment, and had higher levels of brain natriuretic peptide compared to the diagnosed dementia group, but the risks of malnutrition and pressure ulcers were similar to the dementia group. CONCLUSIONS: Unnoted cognitive impairment is common in nursing home residents and may conceal other potentially treatable conditions such as heart failure. The results highlight a need to pay increased attention to cognitive impairment among nursing home residents.

Morbidity and mortality in very old individuals with subsyndromal depression: an 8-year prospective study.

OBJECTIVES: Both morbidity and mortality are elevated for individuals with subsyndromal depression (SSD) compared to non-depression (ND) in those of younger ages, but scientific studies are scarce for very old individuals. The aim of this study was therefore to compare the morbidity and mortality in very old individuals with SSD and ND. DESIGN AND SETTING: An 8-year prospective population-based study was undertaken on 85-year-old individuals in Sweden. MEASUREMENTS: Data were collected from postal questionnaires and clinical assessments at baseline, after 1, 5, and 8 years. Depressive symptoms were measured with Geriatric Depression Scale and the results were classified into ND, SSD, and syndromal depression. Mortality was investigated using multivariable cox regressions, and variables of morbidity were investigated using linear mixed models. RESULTS: Compared to ND, in people with SSD, mortality was elevated in the univariate regression, but this association vanished when controlling for relevant covariates. Morbidity was elevated with regard to basic activities of daily living (ADLs), instrumental ADLs, loneliness, self-perceived health, and depressive symptoms for individuals with SSD compared to ND, whereas cognitive speed, executive functions, and global cognitive function were not significantly impaired when adjusting for covariates. CONCLUSIONS: SSD among very old individuals is longitudinally associated with elevated morbidity but not mortality, when controlling for relevant covariates. Considering the high prevalence of SSD and the demographic development of increasing numbers of very old people, the findings highlight the need to develop clinical and societal strategies to prevent SSD and associated negative outcomes.

Direct Costs of Very Old Persons with Subsyndromal Depression: A 5-Year Prospective Study.

OBJECTIVES: This study aimed to compare, over a 5-year period, the prospective direct healthcare costs and service utilization of persons with subsyndromal depression (SSD) and non-depressive persons (ND), in a population of very old persons. A second aim was to develop a model that predicts direct healthcare costs in very old persons with SSD. DESIGN AND SETTING: A prospective population-based study was undertaken on 85-year-old persons in Sweden. MEASUREMENTS: Depressiveness was screened with the Geriatric Depression Scale at baseline and at 1-year follow-up, and the results were classified into ND, SSD, and syndromal depression. Data on individual healthcare costs and service use from a 5-year period were derived from national database registers. Direct costs were compared between categories using Mann-Whitney U tests, and a prediction model was identified with linear regression. RESULTS: For persons with SSD, the direct healthcare costs per month of survival exceeded those of persons with ND by a ratio 1.45 (€634 versus €436), a difference that was significant even after controlling for somatic multimorbidity. The final regression model consisted of five independent variables predicting direct healthcare costs: male sex, activities of daily living functions, loneliness, presence of SSD, and somatic multimorbidity. CONCLUSIONS: SSD among very old persons is associated with increased direct healthcare costs independently of somatic multimorbidity. The associations between SSD, somatic multimorbidity, and healthcare costs in the very old need to be analyzed further in order to better guide allocation of resources in health policy.

Differences in levels of albumin, ALT, AST, γ-GT and creatinine in frail, moderately healthy and healthy elderly individuals.

BACKGROUND: Reference intervals are widely used as decision tools, providing the physician with information about whether the analyte values indicate ongoing disease process. Reference intervals are generally based on individuals without diagnosed diseases or use of medication, which often excludes elderly. The aim of the study was to assess levels of albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and γ-glutamyl transferase (γ-GT) in frail, moderately healthy and healthy elderly indivuduals. METHODS: Blood samples were collected from individuals >80 years old, nursing home residents, in the Elderly in Linköping Screening Assessment and Nordic Reference Interval Project, a total of 569 individuals. They were divided into three cohorts: frail, moderately healthy and healthy, depending on cognitive and physical function. Albumin, ALT, AST, creatinine and γ-GT were analyzed using routine methods. RESULTS: Linear regression predicted factors for 34% of the variance in albumin were activities of daily living (ADL), gender, stroke and cancer. ADLs, gender and weight explained 15% of changes in ALT. For AST levels, ADLs, cancer and analgesics explained 5% of changes. Kidney disease, gender, Mini Mental State Examination (MMSE) and chronic obstructive pulmonary disease explained 25% of the variation in creatinine levels and MMSE explained three per cent of γ-GT variation. CONCLUSIONS: Because a group of people are at the same age, they should not be assessed the same way. To interpret results of laboratory tests in elderly is a complex task, where reference intervals are one part, but far from the only one, to take into consideration.

Prevalence of the apolipoprotein E ε4 allele in amyloid ß positive subjects across the spectrum of Alzheimer's disease.

INTRODUCTION: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid ß (Aß) pathology. METHODS: We included 3451 Aß+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. RESULTS: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aß+ cognitively normal and Aß+ mild cognitive impairment (P < .05) but not in Aß+ AD dementia (P = .66). The prevalence was highest in Northern Europe but did not vary by sex or education. DISCUSSION: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aß pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.

Markers of subsyndromal depression in very old persons.

OBJECTIVE: To investigate factors associated with subsyndromal depression (SSD) in very old persons, and to develop a model for prediction of SSD among very old persons. METHODS: A cross-sectional, population-based study was undertaken on 85-year-old persons in Sweden. Data were collected from a postal questionnaire, assessments in the participants' homes and at reception visits. Depressiveness was screened with GDS-15 (Geriatric Depression Scale), and the results were classified into three outcome categories: non-depression (ND), SSD and syndromal depression. Data were analysed with binary logistic, ordinal logistic and linear regression. RESULTS: With univariate logistic regression 20 factors associated with SSD were identified in very old persons, and the four hypothesized domains--sociodemographic factors, declining physical functioning, neuropsychiatric factors and existential factors--significantly related to SSD. The multivariate logistic model included seven independent factors that increase the likelihood of SSD instead of ND (lower self-perceived health, life not meaningful, problems with self-care, use of tranquilizing medication, no contact with neighbours, history of affective disorder and history of stroke). The ordinal logistic and the linear regression models resulted in seven partly different factors for predicting SSD and depressiveness, in the very old. CONCLUSIONS: The identified markers may help clinicians with the detection, prevention and treatment of SSD in very old persons. The findings indicate the importance of a comprehensive functional approach to diagnosing and treating depressiveness in this population, and the findings might be interpreted as offering support for the coexistence of a dimensional and a categorical view on depressive disorders.

Cognitive impairment and its consequences in everyday life: experiences of people with mild cognitive impairment or mild dementia and their relatives.

BACKGROUND: The aim of this study was to explore experiences of cognitive impairment, its consequences in everyday life and need for support in people with mild cognitive impairment (MCI) or mild dementia and their relatives. METHODS: A qualitative approach with an explorative design with interviews was chosen. The participants included five people with MCI and eight people with mild dementia and their relatives. All participants were recruited at a geriatric memory clinic in Sweden. The Grounded Theory method was used. RESULTS: The following categories emerged: noticing cognitive changes; changed activity patterns; coping strategies; uncertainty about own ability and environmental reactions; support in everyday life; support from the healthcare system; consequences in everyday life for relatives; and support for relatives. The main findings were that people with MCI and dementia experienced cognitive changes that could be burdensome and changed activity patterns. Most of them, however, considered themselves capable of coping on their own. The relatives noticed cognitive changes and activity disruptions to a greater extent and tried to be supportive in everyday life. Degree of awareness varied and lack of awareness could lead to many problems in everyday life. CONCLUSIONS: Perceived cognitive impairment and its consequences in everyday life were individual and differed among people with MCI or dementia and their relatives. Thus, healthcare professionals must listen to both people with cognitive impairment and their relatives for optimal individual care planning. Support such as education groups and day care could be more tailored towards the early stages of dementia.

Proteasome inhibition induces stress kinase dependent transport deficits--implications for Alzheimer's disease.

Alzheimer's disease (AD) is characterized by accumulation of two misfolded and aggregated proteins, ß-amyloid and hyperphosphorylated tau. Both cellular systems responsible for clearance of misfolded and aggregated proteins, the lysosomal and the proteasomal, have been shown to be malfunctioning in the aged brain and more so in patients with neurodegenerative diseases, including AD. This malfunction could be contributing to ß-amyloid and tau accumulation, eventually aggregating in plaques and tangles. We have investigated the impact of decreased proteasome activity on tau phosphorylation as well as on microtubule stability and transport. To do this, we used our recently developed neuronal model where human SH-SY5Y cells obtain neuronal morphology and function through differentiation. We found that exposure to low doses of the proteasome inhibitor MG-115 caused tau phosphorylation, microtubule destabilization and disturbed neuritic transport. Furthermore, reduced proteasome activity activated several proteins implicated in tau phosphorylation and AD pathology, including c-Jun N-terminal kinase, c-Jun and extracellular signal-regulated protein kinase (ERK) 1/2. Restoration of the microtubule transport was achieved by inhibiting ERK 1/2 activation, and simultaneous inhibition of both ERK 1/2 and c-Jun reversed the proteasome inhibition-induced tau phosphorylation. Taken together, this study suggests that a decrease in proteasome activity can, through activation of c-Jun and ERK 1/2, result in several events related to neurodegenerative diseases. Restoration of proteasome activity or modulation of ERK 1/2 and c-Jun function can open new treatment possibilities against neurodegenerative diseases such as AD.

Spreading of amyloid-ß peptides via neuritic cell-to-cell transfer is dependent on insufficient cellular clearance.

The spreading of pathology through neuronal pathways is likely to be the cause of the progressive cognitive loss observed in Alzheimer's disease (AD) and other neurodegenerative diseases. We have recently shown the propagation of AD pathology via cell-to-cell transfer of oligomeric amyloid beta (Aß) residues 1-42 (oAß1-42) using our donor-acceptor 3-D co-culture model. We now show that different Aß-isoforms (fluorescently labeled 1-42, 3(pE)-40, 1-40 and 11-42 oligomers) can transfer from one cell to another. Thus, transfer is not restricted to a specific Aß-isoform. Although different Aß isoforms can transfer, differences in the capacity to clear and/or degrade these aggregated isoforms result in vast differences in the net amounts ending up in the receiving cells and the net remaining Aß can cause seeding and pathology in the receiving cells. This insufficient clearance and/or degradation by cells creates sizable intracellular accumulations of the aggregation-prone Aß1-42 isoform, which further promotes cell-to-cell transfer; thus, oAß1-42 is a potentially toxic isoform. Furthermore, cell-to-cell transfer is shown to be an early event that is seemingly independent of later appearances of cellular toxicity. This phenomenon could explain how seeds for the AD pathology could pass on to new brain areas and gradually induce AD pathology, even before the first cell starts to deteriorate, and how cell-to-cell transfer can act together with the factors that influence cellular clearance and/or degradation in the development of AD.

The cerebrospinal fluid "Alzheimer profile": easily said, but what does it mean?

BACKGROUND: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-ß1-42 (Aß42), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimer's disease (AD). METHODS: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). RESULTS: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/Aß42 ratio and 0.08 for the p-tau/Aß42 ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/Aß42 ratio. CONCLUSIONS: A tau/Aß42 ratio of >0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.

Spreading of neurodegenerative pathology via neuron-to-neuron transmission of ß-amyloid.

Alzheimer's disease (AD) is the major cause of dementia. During the development of AD, neurofibrillary tangles progress in a fixed pattern, starting in the transentorhinal cortex followed by the hippocampus and cortical areas. In contrast, the deposition of ß-amyloid (Aß) plaques, which are the other histological hallmark of AD, does not follow the same strict spatiotemporal pattern, and it correlates poorly with cognitive decline. Instead, soluble Aß oligomers have received increasing attention as probable inducers of pathogenesis. In this study, we use microinjections into electrophysiologically defined primary hippocampal rat neurons to demonstrate the direct neuron-to-neuron transfer of soluble oligomeric Aß. Additional studies conducted in a human donor-acceptor cell model show that this Aß transfer depends on direct cellular connections. As the transferred oligomers accumulate, acceptor cells gradually show beading of tubulin, a sign of neurite damage, and gradual endosomal leakage, a sign of cytotoxicity. These observations support that intracellular Aß oligomers play a role in neurodegeneration, and they explain the manner in which Aß can drive disease progression, even if the extracellular plaque load is poorly correlated with the degree of cognitive decline. Understanding this phenomenon sheds light on the pathophysiological mechanism of AD progression. Additional elucidation will help uncover the detailed mechanisms responsible for the manner in which AD progresses via anatomical connections and will facilitate the development of new strategies for stopping the progression of this incapacitating disease.

Aspects of awareness in patients with Alzheimer's disease.

BACKGROUND: The purpose of the present study was to gain insight into Alzheimer's disease (AD) patients' perception of the world through the study of a few aspects of awareness. The aspects in focus of the study were disease awareness, metacognition, managing of everyday life, and as a complement, the agreement (calibration) between patients and their spouses on the studied aspects was considered. METHOD: A mixed-method evaluation design was used involving 15 AD patients, their spouses, and 15 elderly healthy control subjects. The study comprised both a semistructured interview (AD patients and spouse) and a neuropsychological assessment (AD patients and control subjects). RESULTS: The patients were aware of their disease and able to report on their illness. Despite this awareness, they were unable to realize and manage the practical and cognitive implications of their impairment. The results also indicate that patients and spouses were not well calibrated regarding thoughts about the disease and problems in handling the cognitive deterioration. CONCLUSIONS: The findings of our study have relevance to patients' well being and how they manage everyday life. An open dialogue on these issues between spouses and in the care for AD patients would hopefully enhance quality of life for all parties involved.

Multimorbidity patterns of and use of health services by Swedish 85-year-olds: an exploratory study.

BACKGROUND: As life expectancy continues to rise, more elderly are reaching advanced ages (≥80 years). The increasing prevalence of multimorbidity places additional demands on health-care resources for the elderly. Previous studies noted the impact of multimorbidity on the use of health services, but the effects of multimorbidity patterns on health-service use have not been well studied, especially for very old people. This study determines patterns of multimorbidity associated with emergency-room visits and hospitalization in an 85-year-old population. METHODS: Health and living conditions were reported via postal questionnaire by 496 Linköping residents aged 85 years (189 men and 307 women). Diagnoses of morbidity were reviewed in patients' case reports, and the local health-care register provided information on the use of health services. Hierarchical cluster analysis was applied to evaluate patterns of multimorbidity with gender stratification. Factors associated with emergency-room visits and hospitalization were analyzed using logistic regression models. RESULTS: Cluster analyses revealed five clusters: vascular, cardiopulmonary, cardiac (only for men), somatic-mental (only for men), mental disease (only for women), and three other clusters related to aging (one for men and two for women). Heart failure in men (OR = 2.4, 95% CI = 1-5.7) and women (OR = 3, 95% CI = 1.3-6.9) as a single morbidity explained more variance than morbidity clusters in models of emergency-room visits. Men's cardiac cluster (OR = 1.6; 95% CI = 1-2.7) and women's cardiopulmonary cluster (OR = 1.7, 95% CI = 1.2-2.4) were significantly associated with hospitalization. The combination of the cardiopulmonary cluster with the men's cardiac cluster (OR = 1.6, 95% CI = 1-2.4) and one of the women's aging clusters (OR = 0.5, 95% CI = 0.3-0.8) showed interaction effects on hospitalization. CONCLUSION: In this 85-year-old population, patterns of cardiac and pulmonary conditions were better than a single morbidity in explaining hospitalization. Heart failure was superior to multimorbidity patterns in explaining emergency-room visits. A holistic approach to examining the patterns of multimorbidity and their relationships with the use of health services will contribute to both local health care policy and geriatric practice.

A quick test of cognitive speed (AQT): usefulness in dementia evaluations in primary care.

OBJECTIVE: To validate A Quick Test of Cognitive Speed (AQT) as an instrument in diagnostic dementia evaluations against final clinical diagnosis and compare AQT with the Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT) in primary care. DESIGN: Primary health care cohort survey. SETTING: Four primary health care centres and a geriatric memory clinic in Sweden. PATIENTS: 81 patients (age 65 and above) were included: 52 with cognitive symptoms and 29 presumed cognitively healthy. None of the patients had a previous documented dementia diagnosis. All patients performed MMSE, CDT, and AQT at the primary health care clinic and were referred for extensive neuropsychological testing at a memory clinic. AQT was validated against final clinical diagnosis determined by a geriatric specialist and a neuropsychologist. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratios, correlation data, and receiver operating characteristic (ROC). RESULTS: For MMSE, sensitivity and specificity was 0.587 and 0.909; CDT 0.261 and 0.879; and AQT 0.783 and 0.667, respectively. For the combination of MMSE and CDT, sensitivity and specificity was 0.696 and 0.788, for MMSE and AQT 0.913 and 0.636. The ROC curve for AQT showed an area under curve (AUC) of 0.773. CONCLUSION: Our results suggest AQT is a usable test for dementia assessments in primary care. Sensitivity for AQT is superior to CDT, equivalent to MMSE, and comparable to the combination MMSE and CDT. MMSE in combination with AQT improves sensitivity. Because AQT is user-friendly and quickly administered, it could be applicable for primary care settings.

Olympic boxing is associated with elevated levels of the neuronal protein tau in plasma.

OBJECTIVES: The aim of this study was to investigate if olympic (amateur) boxing is associated with elevation of brain injury biomarkers in peripheral blood compared to controls. MATERIALS AND METHODS: Thirty olympic boxers competing in at least 47 bouts were compared to 25 controls. Blood was collected from the controls at one occasion and from the boxers within 1-6 days after a bout and after a rest period of at least 14 days. Tau concentration in plasma was determined using a novel single molecule ELISA assay and S-100B, glial fibrillary acidic protein, brain-derived neurotrophic factor and amyloid ß 1-42 were determined using standard immunoassays. RESULTS: None of the boxers had been knocked-out during the bout. Plasma-tau was significantly increased in the boxers after a bout compared to controls (mean ± SD, 2.46 ± 5.10 vs. 0.79 ± 0.961 ng L(-1), p = 0.038). The other brain injury markers did not differ between the groups. Plasma-tau decreased significantly in the boxers after a resting period compared to after a bout (p = 0.030). CONCLUSIONS: Olympic boxing is associated with elevation of tau in plasma. The repetitive minimal head injury in boxing may lead to axonal injuries that can be diagnosed with a blood test.

A novel ARC gene polymorphism is associated with reduced risk of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease, and is clinically characterized by cognitive disturbances and the accumulation of the amyloid ß (Aß) peptides in plaques in the brain. Recent studies have shown the links between AD and the immediate-early gene Arc (activity-regulated cytoskeleton-associated protein), involved in synaptic plasticity and memory consolidation. For example, AD mouse models show a decreased expression of Arc mRNA in the brain. In additional, acute Aß application to brain slices leads to a widespread ARC protein diffusion, unlike the normal defined localization to synapses. In this study, we investigated genetic variation in human ARC and the risk of developing AD. To this end, we genotyped 713 subjects diagnosed with AD and 841 controls without dementia. ARC was sequenced in a group of healthy individuals, and seven previously known SNPs and three novel SNPs were identified. Two of the newly found SNPs were intronic and one, +2852(G/A), was located in the 3'UTR. Three tag SNPs were selected, including the novel SNP +2852(G/A), to relate to risk of AD, Mini Mental State Examination (MMSE) scores and cerebrospinal fluid (CSF) biomarker levels of total tau (T-tau), hyperphosphorylated tau181 (P-tau(181)) and Aß(1-42). The AA genotype of the newly found 3'-UTR SNP +2852(A/G), was associated with a decreased risk of AD (p (c) = 0.005; OR = 0.74; 95 % CI: 0.61-0.89). No associations of single SNPs or haplotypes with MMSE score or CSF biomarkers were found. Here we report a novel ARC SNP associated with a reduced risk of developing AD. To our knowledge, this is the first study associating a gene variant of ARC with any disease. The location of the SNP within the 3'UTR indicates that dendritic targeting of ARC mRNA could be involved in the molecular mechanisms underlying this protective function. However, further investigation of the importance of this SNP for ARC function, ARC processing and the pathology of AD is needed.