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The Systolic Blood Pressure Intervention Trial (SPRINT) compared the clinical outcomes between target systolic blood pressure (SBP) levels between 140 and 120 mmHg or lower. Both,the 2017 ACC/AHA and the 2018 ESC/ESH guidelines in hypertension are derived from the SPRINT trial and advise initiation and/or intensification of treatment at lower blood pressure thresholds. The ACC/AHA guidance supersedes the 2014 Eight Joint National Committee guideline (JNC-8) which advised initiation of treatment when the BP was 140/90 mmHg or higher; in adults 60 years or over, the target was 150/90 mmHg. Compared to JNC-8, the new guidelines lower the SBP target by 10 mmHg in patients under age of 60 years, and by 20 mmHg in the elderly. We performed a qualitative multi-dimensional analysis in order to answer two key questions: will the new guidelines deliver the stated benefits? and, will translation to the clinic be simple, risk-free, and affordable? A major investment by national healthcare administrations will be necessary for the initiation and support of this program but this decision can only be justified by a valid expectation of clinical benefit. At this time, a definitive answer is not available and a "wait and see" attitude appears appropriate and reasonable. In the interim, efforts are best directed to the immediate problem of untreated hypertension worldwide. [ABSTRACT FROM AUTHOR]

Background: The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to improve synapse formation and function in patients with Alzheimer's disease (AD). Two double-blind randomized controlled trials (RCT) with Souvenaid of 12 and 24 week duration (Souvenir I and Souvenir II) showed that memory performance was improved in drug-naïve mild AD patients, whereas no effects on cognition were observed in a 24-week RCT (S-Connect) in mild to moderate AD patients using AD medication. Souvenaid was well-tolerated in all RCTs. Objective: In this 24-week open-label extension (OLE) study to the 24-week Souvenir II RCT, long-term safety and intake adherence of the medical food Souvenaid was evaluated. Methods: Patients with mild AD (n = 201) received Souvenaid once-daily during the OLE. Main outcome parameters were safety and product intake adherence. The memory domain z-score from a revised neuropsychological test battery was continued as exploratory parameter. Results: Compared to the RCT, a similar (low) incidence and type of adverse events was observed, being mainly (68.3%) of mild intensity. Pooled data (RCT and OLE) showed that 48-week use of Souvenaid was well tolerated with high intake adherence (96.1%). Furthermore, a significant increase in the exploratory memory outcome was observed in both the active-active and control-active groups during Souvenaid intervention. Conclusion: Souvenaid use for up to 48-weeks was well tolerated with a favorable safety profile and high intake adherence. The findings in this OLE study warrant further investigation toward the long-term safety and efficacy of Souvenaid in a well-controlled, double-blind RCT. [ABSTRACT FROM AUTHOR]

Background: Studies on the systemic availability of nutrients and nutritional status in Alzheimer's disease (AD) are widely available, but the majority included patients in a moderate stage of AD. Objective: This study compares the nutritional status between mild AD outpatients and healthy controls. Methods: A subgroup of Dutch drug-naïve patients with mild AD (Mini-Mental State Examination (MMSE) &nvge;20) from the Souvenir II randomized controlled study (NTR1975) and a group of Dutch healthy controls were included. Nutritional status was assessed by measuring levels of several nutrients, conducting the Mini Nutritional Assessment (MNA®) questionnaire and through anthropometric measures. Results: In total, data of 93 healthy cognitively intact controls (MMSE 29.0 [23.0-30.0]) and 79 very mild AD patients (MMSE = 25.0 [20.0-30.0]) were included. Plasma selenium (p < 0.001) and uridine (p = 0.046) levels were significantly lower in AD patients, with a similar trend for plasma vitamin D (p = 0.094) levels. In addition, the fatty acid profile in erythrocyte membranes was different between groups for several fatty acids. Mean MNA screening score was significantly lower in AD patients (p = 0.008), but not indicative of malnutrition risk. No significant differences were observed for other micronutrient or anthropometric parameters. Conclusion: In non-malnourished patients with very mild AD, lower levels of some micronutrients, a different fatty acid profile in erythrocyte membranes and a slightly but significantly lower MNA screening score were observed. This suggests that subtle differences in nutrient status are present already in a very early stage of AD and in the absence of protein/energy malnutrition. [ABSTRACT FROM AUTHOR]

In a world where 12% of the population, and 22% of that of more developed regions, will be older than 65 years by 2030, new targeted programs and social protections will be needed for older people in many countries. As economic and human resources become more scarce, efficient instruments are needed to realize sustainable health care for these large populations of older subjects. To address this need a new assessment instrument was developed. The core of the instrument consists of focused geriatric assessment by a health or social care practitioner working in primary or community care, most often a nurse. The assessment data result in an efficiently targeted care and welfare action plan based on the patients' priorities This instrument was initially developed, tested and spread within Europe, and then in validation studies across all WHO regions of the world. Because of the urgent societal questions on quality and sustainability of primary health care, especially for older people, we briefly review and summarize the development and evidence base of the instrument, which was called EASY-Care Standard. In a series of studies across many populations it proved to have high acceptability, reliability, validity and cost-effectiveness. Therefore, EASY-Care has great potential as a universal tool for global use in promoting independence in old age, and can make an important contribution to the quality and sustainability of health and social care in our aging societies [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to assess the feasibility and reproducibility of a simple and nonobtrusive repeated sit-stand maneuver to assess cerebral autoregulation (CA) in healthy old subjects >70 years. In 27 subjects aged 76 (SD 4) years, we continuously measured blood pressure using photoplethysmography and cerebral blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasonography) during 5min of sitting rest and again during repeated sit-stand maneuvers at 10 s (0.05Hz) and 5 s (0.1Hz) intervals. In 11 randomly selected subjects, these measurements were repeated after 3 months. Both maneuvers induced substantial periodic oscillations in pressure and flow. For example, the maneuvers at 0.05Hz increased the power spectral density (magnitude) of blood pressure and cerebral blood flow velocity oscillations with 16.3 (mm Hg)2 and 14.5 (cm/s)2, respectively (p <0.001). These larger oscillations led to an increase in transfer function coherence compared with spontaneous oscillations from 0.46 to 0.60 for 0.05Hz maneuvers and from 0.56 to 0.76 for 0.1Hz maneuvers (p <0.01), allowing for more confident assessment of CA through transfer function phase and gain. This increased coherence was not associated with improved reproducibility however. In conclusion, we were able to investigate CA in old patients using these repeated sit-stand maneuvers, which, compared with spontaneous oscillations, produced a stronger and more clinically relevant hemodynamic challenge for CA. (E-mail: j.claassen@ger.umcn.nl) [Copyright &y& Elsevier]

Abstract: Many gait and balance variables depend on gait velocity, which seriously hinders the interpretation of gait and balance data derived from walks at different velocities. However, as far as we know there is no widely accepted method to correct for effects of gait velocity on other gait and balance measures. We developed a simple statistical method to obtain gait and balance variables for each participant that are independent of gait velocity. The first step of our standardization method was the transformation of the gait and balance data to obtain a normal distribution and decrease the influence of outliers. Thereafter, we constructed a formula, based on regression analysis that described how these data varied with gait velocity in each participant during walking without an additional task. Last, this formula was used to standardize the gait and balance data for the effect of gait velocity for each individual participant. As example we present the analysis of mediolateral displacements of the trunk in fit elderly people during walking with and without a dual task. [Copyright &y& Elsevier]

Editorial. Deals with malnutrition research. Categories of malnutrition; Reason for considering malnutrition as a geriatric syndrome; Syndromes related to malnutrition.

Background: Visual estimation of age can be used as a measure of biological age (BA) and has become useful in predicting life expectancy.Objective: The aim of this study was to quantify the interrater agreement of experienced geriatricians in visual estimation of BA.Methods: In a prospective controlled study, 4 experienced geriatricians estimated the BA of 43 elderly subjects (mean age 82.5 +/- 6.0 years) during a short standardized interview, using a checklist of age-associated changes in appearance, communication and mobility. Interrater agreement was calculated by analysis of variance and expressed as the intra-class coefficient of correlation (ICCC).Results: The ICCC of the BA estimation was 0.76 (p < 0.001). Within-subject standard deviation of the estimate was 3. 4 years. On average, BA was 4.8 (+/-4.4) years lower than chronological age (p < 0.001).Conclusion: Visual estimation of BA based on a simple checklist has a good interrater agreement and therefore should be part of geriatric assessment. [ABSTRACT FROM AUTHOR]

Background: Even though poor lighting at nighttime is an important risk factor for falls (and most falls occur during the night), lighting interventions to improve nightly lighting from bed to bathroom are rarely evaluated for fall prevention.Objective: We tested the hypothesis that an automated guiding light would reduce nightly fear of falling (FOF) and increase sleep quality of community-dwelling older people.Methods: This study had a pragmatic uncontrolled before-after design, including participants during a period of 8 months if they (i) were aged at least 65 years, (ii) ambulated independently at night, and (iii) had no cognitive or audiovisual impairments obstructing outcome measurement. Automated LED strips (GightTM) were installed in the participants' homes. The primary outcome measure was overnight FOF on a scale of 0-10. Secondary outcome measures included sleep quality on a scale of 0-10 and fall rate. Additionally, a sample of participants was interviewed about their experiences with Gight.Results: Sixty-four participants were included (mean age: 80.8 ± 8.1 years; 89% living independently). Mean study length was 118 days (range: 30-231). In the intention-to-treat analysis, overnight FOF declined from 5.5 ± 3.0 to 3.8 ± 3.2 (p = 0.001), and sleep quality increased from 6.7 ± 2.4 to 7.4 ± 1.7 (p = 0.012). The fall rate during the study was too low to detect changes. Participants appreciated Gight (8.4 ± 0.8 on a scale of 10), and the majority (57%) reported a subjective decrease in FOF.Conclusion: Gight shows promising results for overnight FOF and sleep quality, but the effect of lighting interventions on fall rate should be evaluated further before widespread implementation. [ABSTRACT FROM AUTHOR]

Previous studies have shown that older patients benefited less than younger patients from surgical treatment for colorectal cancer (CRC). However, CRC care has advanced over time, and it is time to assess whether the difference in postoperative mortality between older and younger CRC patients is still present. Patients with primary stage I-III CRC diagnosed between 2005 and 2016 were selected from the Netherlands Cancer Registry (N = 111,778). Trends in postoperative mortality and 1-year postoperative relative survival (RS) were analysed, stratified according to age (<75 versus ≥75 years) and tumour location (colon versus rectum). One-year postoperative RS was analysed to correct for background mortality in the older population. Between 2005 and 2016, 30-day postoperative mortality showed a stronger decrease for older patients (from 10.0% to 4.0% for colon cancer [p < 0.001] and from 8.3% to 2.7% for rectal cancer [p < 0.001]) compared with younger patients (from 2.0% to 0.9% for colon cancer [p < 0.001] and from 1.4% to 0.7% for rectal cancer [p = 0.01]). Between 2005 and 2016, also 1-year RS increased more for older patients (from 84.8% to 94.6% for colon cancer and from 86.1% to 97.2% for rectal cancer) compared with younger patients (from 94.0% to 97.8% for colon cancer and from 96.3% to 98.8% for rectal cancer). Between 2005 and 2016, differences in postoperative mortality between older and younger CRC patients decreased. One-year postoperative RS was almost equal for older and younger patients in 2015–2016. This information is crucial for shared decision-making on surgical treatment. • Differences in mortality between older and younger CRC patients decreased. • One-year relative survival became nearly equal for older and younger patients. • Previous literature is no longer representative of the current clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Respiratory, and cardio-cerebrovascular health-related diseases significantly threaten human health and together with air pollution form a complex pathophysiological system. Other complex biological systems show that increased variance and autocorrelations in time series may act as valid early warning signals for critical transitions. On population level, we determined the likelihood that increased variance and autocorrelation of hospital visit on cardiopulmonary disease preceded critical transitions in population health by human-pollution interactions. We investigated long-term hospital visits from a hospital in Nanjing City, China during 2006–2016 for the most important cardiopulmonary diseases likely to be influenced by air pollution: cerebrovascular accident disease (CVAD), coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), lung cancer disease (LCD), and the grouped categories of respiratory system disease (RESD) and cardio-cerebrovascular system disease (CCD). The time series of standard deviations (SDs) and autocorrelation at-lag-1 (AR-1) were studied as potential Early-Warning Indicators (EWIs) of transitions in population health. Elevated SDs provided an early warning for critical transitions in visit for LCD and overall CCD and CVAD, for the period of 2012–2013, after which a real transition of increased visit occurred for these disease categories. Statistical testing showed that these SDs were significantly increased (p < 0.1). The long-term air pollution together with intermittent pollution episodes may have triggered critical transitions in population health for cardiopulmonary disease. It is recommended to consider significant increases in variability in time series of relevant system parameters, such as visit, as early warning signs for future transitions in populations' health states. Graphical abstract Unlabelled Image Highlights • The human-pollution interaction can be considered as a complex nonlinear system. • The likelihood of loss of resilience of cardiopulmonary health was investigated. • Elevated standard deviation provides an early warning for critical transitions. • Air pollution may play a pivotal role for transitions in population health. [ABSTRACT FROM AUTHOR]

Objective: To identify determinants of older patients' perceptions of involvement in decision-making on colorectal (CRC) or pancreatic cancer (PC) treatment, and to compare these with determinants of observers' perceptions.Methods: Patients' perceptions of involvement were constructed by the 9-item SDM questionnaire (SDM-Q-9) and a Visual Analogue Scale for Involvement (VAS-I). Observers' perceptions were constructed by the OPTION5, OPTION12, and MAPPIN'SDM. Convergent validities were calculated between the patient-sided and observer instruments using Spearman's correlation coefficient. Linear regression was used to identify determinants per criterion.Results: 58 CRC and 22 PC patients were included (mean age: 71.8 ± 5.2 years, 45.0% female). No significant correlations were found between the patient-sided and observer instruments. Patients' impression of involvement was influenced by patient characteristics such as quality of life and satisfaction, while observers' perceptions mainly referred to encounter characteristics such as the mean duration of consultations and general communication skills.Conclusion: Due to evident differences in determinants, older CRC/PC patients' and observers' perceptions of involvement should both be collected in evaluating the quality of medical decision-making.Practice Implications: General communication skills should be integrated in SDM training interventions. New SDM measurement tools for patients are needed to sufficiently discriminate between the constructs of involvement and satisfaction. [ABSTRACT FROM AUTHOR]

Purpose of study The first aim is to evaluate, in a sub-study, the recruitment process of the Senior Step Study, which was an intervention study on the self-management of mobility and fall risk; the second aim is to explore the reasons mentioned by older people, from three different settings, for (not) participating. Methods Subjects were community-dwelling older persons, residents of homes for the elderly, and older persons regularly visiting community centres. The effectiveness of different recruitment procedures was analysed for each setting separately. We also analysed reasons for accepting and declining participation between the settings. Results The total inclusion rate was 27.9%. A personal initial approach (i.e., first contact was face-to-face or in a group meeting) did not improve the inclusion rate. More subjects consented to participate after an introductory meeting (which was planned after the first face-to-face contact) compared to persons not having one (p < 0.01). At different settings, subjects gave different reasons for participation. No differences were found in the reasons for refusing participation. Especially in homes for the elderly, people refused to participate because the research was too burdensome. Conclusions The inclusion rates in this study are comparable to other self-management studies with older people. An introductory meeting during which the study design and benefits of participating are explained and formal interim evaluations of the recruitment process may benefit recruitment. Recruiting older persons for self-management tasks is possible with the appropriate recruitment process, enabling more research on this increasingly important research topic. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning four cases of older patients who experienced sudden function decline as a result of infection.

Objectives To assess the feasibility and validity of the International Dementia Alliance ( IDEAL) instrument for Informal Caregivers ( IDEAL- IC), which is based on the IDEAL instrument for professionals ( IDEAL-P), for staging individuals with dementia. Design Cross-sectional. Setting Memory clinic of a university hospital. Participants Informal caregivers of 73 community-dwelling elderly adults referred to a memory clinic and six geriatric registrars. Measurements Caregivers completed the IDEAL- IC; physicians completed the original IDEAL-P and the Clinical Dementia Rating sum of boxes ( CDR- SB). Missing items and floor and ceiling effects were reviewed to assess feasibility. To test construct validity, a priori hypotheses were defined for expected correlations between IDEAL- IC, IDEAL-P, and CDR- SB scores. Results Seventy-three IDEAL- IC instruments were completed, 86% of which had no missing items. Three percent of all 730 individual items were missing. No floor or ceiling effects were detected. CDR scores were 0 7%, 0.5 in 33%, 1 in 27%, 2 in 10%, and unknown in 23%. IDEAL- IC scores correlated highly with IDEAL-P scores (correlation coefficient ( r) = 0.70) and with CDR- SB scores ( r = 0.65) as expected; the difference between these two correlations was smaller than expected. Agreement between IDEAL- IC and IDEAL-P scores was 34% within a range of 1 point difference on 36-point scales, 57% within a range of two points, and 81% within a range of five points. Correlation between IDEAL-P and CDR- SB was very high ( r = 0.85). Conclusion Results of this study indicate good feasibility and high validity of staging dementia by informal caregivers using the IDEAL- IC. [ABSTRACT FROM AUTHOR]

Background: Recent global meta-analyses show that 40% of dementia cases can be attributed to twelve modifiable risk factors.Objective: To investigate how health promotion strategies may differ in specific populations, this study estimated population attributable fractions (PAFs) of these risk factors for dementia in cognitively normal (CN) individuals and individuals with mild cognitive impairment (MCI) in United States and Greek cohorts.Methods: We re-analyzed data from the National Alzheimer's Coordinating Centre (NACC, n = 16,147, mean age 75.2±6.9 years, 59.0% female) and the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD, n = 1,141, mean age 72.9±5.0 years, 58.0% female). PAFs for the total samples and CN and MCI subgroups were calculated based on hazard ratios for the risk of dementia and risk factor prevalence in NACC (9 risk factors) and HELIAD (10 risk factors).Results: In NACC, 2,630 participants developed MCI (25.1%) and 3,333 developed dementia (20.7%) during a mean follow-up of 4.9±3.5 years. Weighted overall PAFs were 19.4% in the total sample, 15.9% in the CN subgroup, and 3.3% in the MCI subgroup. In HELIAD, 131 participants developed MCI (11.2%) and 68 developed dementia (5.9%) during an average follow-up of 3.1±0.86 years. Weighted overall PAFs were 65.5% in the total sample, 65.8% in the CN subgroup and 64.6% in the MCI subgroup.Conclusion: Translation of global meta-analysis data on modifiable risk factors should be carefully carried out per population. The PAFs of risk factors differ substantially across populations, directing health policy making to tailored risk factor modification plans. [ABSTRACT FROM AUTHOR]

Background: Research on new treatments for dementia is gaining pace worldwide in an effort to alleviate this growing health care problem. The optimal evaluation of such interventions, however, calls for a practical and credible patient-reported outcome measure.Objectives: To describe the refinement of the Dementia Quality-of-life Instrument (DQI) and present its revised version.Methods: A prototype of the DQI was adapted to cover a broader range of health-related quality of life (HRQOL) and to improve consistency in the descriptions of its domains. A valuation study was then conducted to assign meaningful numbers to all DQI health states. Pairs of DQI states were presented to a sample of professionals working with people with dementia and a representative sample of the Dutch population. They had to repeatedly select the best DQI state, and their responses were statistically modeled to obtain values for each health state.Results: In total, 207 professionals working with people with dementia and 631 members of the general population completed the paired comparison tasks. Statistically significant differences between the two samples were found for the domains of social functioning, mood, and memory. Severe problems with physical health and severe memory problems were deemed most important by the general population. In contrast, severe mood problems were considered most important by professionals working with people with dementia.Discussion: The DQI is a simple and feasible measurement instrument that expresses the overall HRQOL of people suffering from dementia in a single meaningful number. Current results suggest that revisiting the discussion of using values from the general population might be warranted in the dementia context. [ABSTRACT FROM AUTHOR]

Various studies have shown the efficacy of errorless learning (EL) in teaching patients with dementia a wide variety of skills and everyday tasks, with some studies showing beneficial effects and others reporting limited or no advantage. However, EL procedures vary greatly and, to date, no clinical guidelines or manuals are available. Here, we present a nationwide survey exploring the interest in, and feasibility of, EL in dementia care in The Netherlands. Based on the survey results and available evidence in the literature, we subsequently drafted an EL manual and had this concept manual evaluated in a Delphi round using the AGREE instrument. Forty-five health professionals associated with 22 dementia care facilities in The Netherlands, including those survey respondents who had piloted an EL intervention in accordance with the concept manual and an eight-strong expert panel representing various disciplines, deemed EL to be meaningful and feasible for use in dementia care and their residential facilities. Although our manual was favourably received, future studies are required to examine how EL can best be implemented in clinical practice and to determine the optimal outcome measures and quality indicators to reliably evaluate intervention outcomes and to consider the cost-effectiveness of the approach. [ABSTRACT FROM AUTHOR]

The author looks into the concept of multimorbidity of patients in relation to the improvement of healthcare worldwide. Topics include the importance of understanding the plurality of diseases and its reality, how the operationalization of multimorbidity should be about its causes and consequences, and multimorbidity operationalization as a complex adaptive system's phenomenon.

• Late-onset Alzheimer's disease involves interacting mechanisms across multiple scales. • Systems thinking addresses this complexity via conceptual and computational models. • Quantifying extensive models with data enables multi-factor intervention simulations. • Personalized multi-factor interventions: greater efficacy and synergistic benefits. • Systems thinking promotes knowledge synthesis, iterative model-driven data collection. Despite extensive research efforts to mechanistically understand late-onset Alzheimer's disease (LOAD) and other complex mental health disorders, curative treatments remain elusive. We emphasize the multiscale multicausality inherent to LOAD, highlighting the interplay between interconnected pathophysiological processes and risk factors. Systems thinking methods, such as causal loop diagrams and systems dynamic models, offer powerful means to capture and study this complexity. Recent studies developed and validated a causal loop diagram and system dynamics model using multiple longitudinal data sets, enabling the simulation of personalized interventions on various modifiable risk factors in LOAD. The results indicate that targeting factors like sleep disturbance and depressive symptoms could be promising and yield synergistic benefits. Furthermore, personalized interventions showed significant potential, with top-ranked intervention strategies differing significantly across individuals. We argue that systems thinking approaches can open new prospects for multifactorial precision medicine. In future research, systems thinking may also guide structured, model-driven data collection on the multiple interactions in LOAD's complex multicausality, facilitating theory development and possibly resulting in effective prevention and treatment options [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Cost consciousness in patient care--what is medical education's responsibility?," by M. Cooke in the April 8, 2010 issue.

Objectives: To make an inventory of needs assessment instruments in dementia, to explore the interaction between unmet needs and health-related quality of life (HRQoL) and to relate these to the conceptual model of Maslow's Hierarchy of needs in order to design a dementia-specific model. Methods: Narrative review of literature on (measures of) needs of patients and caregivers and HRQoL determinants important in dementia. Relating these needs to individual goal setting instruments and Maslow's Hierarchy of needs model. Results: The Camberwell Assessment of Needs for the Elderly (CANE) turns out to be a valid tool to assess needs of dementia patients, suitable for research and clinical use. The Carers' Needs Assessment for Dementia (CNA-D) is a valid instrument to assess needs of caregivers. Patients identified significantly fewer needs than (in)formal caregivers. The most important needs, that also determine large part of HRQoL, are need for information; support with regard to symptoms of dementia; social contact and company; and for health monitoring and safety. Goal attainment scaling in dementia is an important but not yet valid outcome measure, with only few data on feasibility in dementia patients. Conclusion: There are several instruments to assess needs of dementia patients and caregivers. Domains of unmet needs and HRQoL overlap. The Hierarchy Model of Needs in Dementia (HMND) offers a new theoretical framework to address the interplay between meeting of needs and improvement of HRQoL in dementia. By identifying unmet needs in dementia-research and focussing on unmet needs in dementia-care, much can be done to improve HRQoL. [ABSTRACT FROM AUTHOR]

Abstract: Comprehensive geriatric assessment (CGA) is a process that consists of a multidimensional data-search and a process of analyzing and linking patient characteristics creating an individualized intervention-plan, carried out by a multidisciplinary team. In general, the positive health care effects of CGA are established, but in oncology both CGA and the presence of geriatric syndromes still have to be implemented to tailor oncological therapies to the needs of elderly cancer patients. In this paper the conceptualization of geriatric syndromes, their relationship to CGA and results of clinical studies using CGA in oncology are summarized. Geriatric syndromes are associated with increased vulnerability and refer to highly prevalent, mostly single symptom states (falls, incontinence, cognitive impairment, dizziness, immobility or syncope). Multifactorial analysis is common in geriatric syndromes and forms part of the theoretical foundation for using CGA. In oncology patients, we reviewed the value of CGA on the following endpoints: recognition of health problems, tolerance to chemotherapy and survival. Most studies performed CGA to identify prognostic factors and did not include an intervention. The ability of CGA to detect relevant health problems in an elderly population is reported consistently but no randomized studies are available. CGA should explore the pre-treatment presence of (in)dependence in Instrumental Activities of Daily Living (IADL), poor or moderately poor quality of life, depressive symptoms and cognitive decline, and thereby may help to predict survival. However, if scored by the Charlson comorbidity-index, comorbidities are not convincingly related to survival. The few studies that included a CGA-linked intervention show inconsistent results with regard to survival but compared to usual care quality of life is improved in the surviving period. Functional performance scores and dependency at home appeared to be independent predictive factors for toxicity, similar to depressive symptoms and polypharmacy. Overall, CGA implements/collects information additional to chronological age and Performance Score. So far in oncology there are no prognostic validation studies reported using geriatric syndromes or information based on CGA in its decision making strategies. [Copyright &y& Elsevier]

The article presents the discussion on danger to public health and the essential life support systems of the planet. Topics include good faith on effective measures relating to cessation of the nuclear arms race at an early date and to nuclear disarmament; and public on both sides of the Iron Curtain about the medical consequences of nuclear war.

An editorial is presented the urgent role of health professionals in addressing the increasing risk of nuclear war, highlighting the inadequacy of current arms control efforts, the catastrophic consequences of nuclear war, and the historical and ongoing efforts of the health community to advocate for nuclear disarmament, while calling for immediate steps and collaborative actions to prevent nuclear conflict and eliminate nuclear weapons.

Abstract: Reports on the value of cerebrospinal fluid (CSF) α-synuclein as a biomarker for dementia with Lewy bodies and Parkinson disease are contradicting. This may be explained by fluctuating CSF α-synuclein concentrations over time. Such fluctuations have been suggested for CSF amyloid β concentrations. Furthermore, a physiological relationship between α-synuclein and amyloid β has been suggested based on in vitro research. We performed repeated CSF sampling in healthy elderly and AD patients and showed that sinusoidal fluctuations in CSF α-synuclein concentrations were not present. Furthermore, we did not find evidence for an interaction between amyloid β and α-synuclein concentrations in CSF. [Copyright &y& Elsevier]

The aim of this study was to investigate whether the effect of physical activity on cognitive function in persons with dementia is moderated by patient characteristics as Apolipoprotein E and dementia type. We included 101 individuals with dementia and calculated the reliable change index to determine the change in global cognition, executive function, episodic memory, working memory, and processing speed before and after a 12-week exercise training. We found a higher treatment-related benefit in episodic memory in persons with non-Alzheimer's disease compared to persons with Alzheimer's disease, and in executive function in individuals with better baseline cognitive function. [ABSTRACT FROM AUTHOR]

Objectives: Previous studies have identified several subgroups (ie, latent trajectories) with distinct disease progression among people with dementia. However, the methods and results were not always consistent. This study aims to perform a coordinated analysis of latent trajectories of cognitive and functional progression in dementia across two datasets.Methods: Included and analyzed using the same statistical approach were 1628 participants with dementia from the US National Alzheimer's Coordinating Center (NACC) and 331 participants with dementia from the Dutch Clinical Course of Cognition and Comorbidity study (4C-Study). Trajectories of cognition and instrumental activities of daily living (IADL) were modeled jointly in a parallel-process growth mixture model.Results: Cognition and IADL tended to decline in unison across the two samples. Slow decline in both domains was observed in 26% of the US sample and 74% of the Dutch sample. Rapid decline in cognition and IADL was observed in 7% of the US sample and 26% of the Dutch sample. The majority (67%) of the US sample showed moderate cognitive decline and rapid IADL decline.Conclusions: Trajectories of slow and rapid dementia progression were identified in both samples. Despite using the same statistical methods, the number of latent trajectories was not replicated and the relative class sizes differed considerably across datasets. These results call for careful consideration when comparing progression estimates in the literature. In addition, the observed discrepancy between cognitive and functional decline stresses the need to monitor dementia progression across multiple domains. [ABSTRACT FROM AUTHOR]

Previous studies have shown large heterogeneity in the progression of dementia, both within and between patients. This heterogeneity offers an opportunity to limit the global and individual burden of dementia through the identification of factors associated with slow disease progression in dementia. We explored the heterogeneity in dementia progression to detect disease, patient, and social context factors related to slow progression. Two longitudinal population-based cohort studies with follow-up across 12 years. 512 people with incident dementia from Stockholm (Sweden) contributed to the Kungsholmen Project and the Swedish National Study of Aging and Care in Kungsholmen. We measured cognition using the Mini-Mental State Examination and daily functioning using the Katz Activities of Daily Living Scale. Latent classes of trajectories were identified using a bivariate growth mixture model. We then used bias-corrected logistic regression to identify predictors of slower progression. Two distinct groups of progression were identified; 76% (n = 394) of the people with dementia exhibited relatively slow progression on both cognition and daily functioning, whereas 24% (n = 118) demonstrated more rapid worsening on both outcomes. Predictors of slower disease progression were Alzheimer's disease (AD) dementia type [odds ratio (OR) 2.07, 95% confidence interval (CI) 1.15-3.71], lower age (OR 0.88, 95% CI 0.83-0.94), fewer comorbidities (OR 0.77, 95% CI 0.66-0.90), and a stronger social network (OR 1.72, 95% CI 1.01-2.93). Lower age, AD dementia type, fewer comorbidities, and a good social network appear to be associated with slow cognitive and functional decline. These factors may help to improve the counseling of patients and caregivers and to optimize the planning of care in dementia. [ABSTRACT FROM AUTHOR]

Objectives: Memory clinics (MCs) have been established to improve diagnosis and treatment of cognitive disorders, including dementia. The aim of this study was to determine the characteristics and working methods of MCs in the Netherlands in 2016. More insight into different working methods can be used to improve the quality of care in Dutch MCs. Additionally, the findings will be compared with earlier results to investigate the development of MCs since 1998.Methods: A survey was sent in 1998, 2004, 2009, and 2017 to all operational Dutch MCs with questions about organization, collaboration, patients, and diagnostic procedures.Results: From 1998 to 2016, the number of MCs increased substantially from 12 to 91. The capacity increased from 1560 patients to 24,388. In 1998, most patients received a dementia diagnosis (85%), while in 2016, half of the patients were diagnosed with milder cognitive problems. MCs are more often part of regional care chains and are better embedded within regional care organizations. Diagnostic tools, such as blood tests (97%), neuropsychological assessment (NPA) (95%), and neuroimaging (92%), were used in nearly all MCs. The number of patients in whom these tools were used differed greatly between MCs (NPA: 5%-100%, neuroimaging: 10%-100%, and CSF: 0.5%-80%). There was an increase in the use of NPA, while the use of neuroimaging, CSF, and EEG/ECG decreased by 8% to 15% since 2009.Conclusions: Since 1998, MCs have developed substantially and outgrown the primarily research-based university settings. They are now accepted as regular care facilities for people with cognitive problems. [ABSTRACT FROM AUTHOR]

The Science and Security Board of the Bulletin of the Atomic Scientists has moved the Doomsday Clock forward to 90 seconds before midnight, indicating an increased risk of nuclear war. The UN Secretary-General has also warned of the current nuclear danger, likening it to the height of the Cold War. The editors of health and medical journals worldwide are calling on health professionals to raise awareness about this threat to public health and the planet's life support systems. They emphasize the inadequacy of current nuclear arms control efforts and urge action to prevent nuclear war. The use of nuclear weapons would have catastrophic consequences, and steps must be taken to address the root cause of the problem by abolishing nuclear weapons. The health community has played a crucial role in previous efforts to reduce the risk of nuclear war and must continue to do so. Health professional associations are called upon to inform their members about the threat and support efforts to reduce the risks of nuclear war. Immediate steps include adopting a no first use policy, taking nuclear weapons off hair-trigger alert, and urging states involved in conflicts to publicly pledge not to use nuclear weapons. The ultimate goal is the elimination of nuclear weapons through negotiations among nuclear-armed states. The health community must work with renewed energy to reduce the risks of nuclear war and eliminate nuclear weapons. [Extracted from the article]

Background: Quality of Life (QoL) is an important outcome measure in dementia, particularly in the context of interventions. Research investigating longitudinal QoL in dementia with Lewy bodies (DLB) is currently lacking.Objective: To investigate determinants and trajectories of QoL in DLB compared to Alzheimer's disease (AD) and controls.Methods: QoL was assessed annually in 138 individuals, using the EQ5D-utility-score (0-100) and the health-related Visual Analogue Scale (VAS, 0-100). Twenty-nine DLB patients (age 69±6), 68 AD patients (age 70±6), and 41 controls (age 70±5) were selected from the Dutch Parelsnoer Institute-Neurodegenerative diseases and Amsterdam Dementia Cohort. We examined clinical work-up over time as determinants of QoL, including cognitive tests, neuropsychiatric inventory, Geriatric Depression Scale (GDS), and disability assessment of dementia (DAD).Results: Mixed models showed lower baseline VAS-scores in DLB compared to AD and controls (AD: β±SE = -7.6±2.8, controls: β±SE = -7.9±3.0, p < 0.05). An interaction between diagnosis and time since diagnosis indicated steeper decline on VAS-scores for AD patients compared to DLB patients (β±SE = 2.9±1.5, p < 0.1). EQ5D-utility-scores over time did not differ between groups. Higher GDS and lower DAD-scores were independently associated with lower QoL in dementia patients (GDS: VAS β±SE = -1.8±0.3, EQ5D-utility β±SE = -3.7±0.4; DAD: VAS = 0.1±0.0, EQ5D-utility β±SE = 0.1±0.1, p < 0.05). No associations between cognitive tests and QoL remained in the multivariate model.Conclusion: QoL is lower in DLB, while in AD QoL shows steeper decline as the disease advances. Our results indicate that non-cognitive symptoms, more than cognitive symptoms, are highly relevant as they impact QoL. [ABSTRACT FROM AUTHOR]

Background: The Older Persons and Informal Caregivers Minimum Data Set (TOPICS-MDS) is a standardized data set that was developed to evaluate the quality of multidimensional geriatric care. There is an inherent need to reduce the number of TOPICS-MDS survey items to core outcomes to allow it to be more easily applied as a patient-reported outcome measure in clinical settings.Objectives: To create a TOPICS-short form (TOPICS-SF) and examine its validity.Methods: Data in the TOPICS-MDS from persons aged 65 years and older in the Netherlands were used for the following analyses. Multiple linear regression analyses were performed to select the items and to derive domain weights of TOPICS-SF. A priori hypotheses were made on the basis of psychometric properties of the full-length TOPICS-MDS preference-weighted score (TOPICS-CEP). The validity of TOPICS-SF was evaluated by 1) examining the meta-correlation of the TOPICS-SF score with TOPICS-CEP and two quality-of-life measures, that is, the Cantril Ladder score and the EuroQol five-dimensional questionnaire utility index, and 2) performing mixed multiple regression of TOPICS-SF scores across key sociodemographic characteristics.Results: TOPICS-SF scores were strongly correlated with the TOPICS-CEP (r = 0.96) and had stronger correlation with the EuroQol five-dimensional questionnaire utility index compared with the Cantril Ladder (r = 0.61 and 0.38, respectively). TOPICS-SF scores were higher among older persons who were married, living independently, and having higher levels of education.Conclusions: We have developed the 22-item TOPICS-SF and demonstrated its validity, supporting its use as a patient-reported outcome measure in geriatric care. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to examine physical activity and sedentary behaviour characteristics of ambulatory and community-dwelling patients with dementia compared to cognitively healthy age-, sex- and weight-matched controls. Methods: In this cross-sectional study, we included community-dwelling dementia patients (n = 45, age 79.6 ± 5.9 years, Mini-Mental State Examination [MMSE] 22.8 ± 3.2) and matched controls (n = 49, age 80.0 ± 7.7 years, MMSE 29.0 ± 1.2). Participants wore a wrist accelerometer for 7 days to assess sedentary time, sedentary bout duration and time spent in very light, light-to-moderate and moderate-to-vigorous physical activities. Results: Relative sedentary time and sedentary bout duration was significantly higher in dementia patients than in controls (median [interquartile range] 57% [49–68] vs. 55% [47–59] and 18.3 [16.4–21.1] min vs. 16.6 [15.3–18.4] min, p = 0.042 and p = 0.008, respectively). In addition, dementia patients spent a lower percentage of their waking time in light-to-moderate and moderate-to-vigorous intensity physical activities (20% [15–23] vs. 22% [18–25] and 5% [2–10] vs. 10% [5–13], p = 0.017 and p = 0.001, respectively). Conclusion: We revealed that dementia patients are more sedentary and perform less physical activity than cognitively healthy controls. This may have clinically important consequences, given the observation that sedentary behaviour and little physical activity independently predict all-cause mortality and morbidity. [ABSTRACT FROM AUTHOR]

Objective: To identify key elements of optimal treatment decision-making for surgeons and older patients with colorectal (CRC) or pancreatic cancer (PC).Methods: Six focus groups with different participants were performed: three with older CRC/PC patients and relatives, and three with physicians. Supplementary in-depth interviews were conducted in another seven patients. Framework analysis was used to identify key elements in decision-making.Results: 23 physicians, 22 patients and 14 relatives participated. Three interacting components were revealed: preconditions, content and facilitators of decision-making. To provide optimal information about treatments' impact on an older patient's daily life, physicians should obtain an overall picture and take into account patients' frailty. Depending on patients' preferences and capacities, dividing decision-making into more sessions will be helpful and simultaneously emphasize patients' own responsibility. GPs may have a valuable contribution because of their background knowledge and supportive role.Conclusion: Stakeholders identified several crucial elements in the complex surgical decision-making of older CRC/PC patients. Structured qualitative research may also be of great help in optimizing other treatment directed decision-making processes.Practice Implications: Surgeons should be trained in examining preconditions and useful facilitators in decision-making in older CRC/PC patients to optimize its content and to improve the quality of shared care. [ABSTRACT FROM AUTHOR]

Objective: Meta-analyses of antidepressant drug treatment trials have found that increasing age is associated with a less favourable outcome. Because the prevalence of geriatric characteristics, like disability, medical co-morbidity, malnutrition, cognitive (dys)function and frailty increase with age and are associated with depression, these characteristics are likely to modify the treatment outcome of antidepressant drugs in late-life depression. This review examines how these five characteristics are taken into account in randomised controlled trials (RCTs) with antidepressant drugs for major depressive disorder in patients aged 60 years or above.Design: A systematic search in PubMED, PsychInfo and EMBASE, from the year 2000 onwards, yielded 27 RCTs, with a total of 6356 subjects with a median age of 71 years. Two reviewers independently assessed whether each characteristic was considered as inclusion or exclusion criterion, descriptive variable, stratification variable, co-variable, outcome measure, or in adverse effect monitoring.Results: Malnutrition and frailty were not taken into account in any study. Disability was used as an outcome measure in five studies. Two studies explicitly included a population with possibly serious medical co-morbidity. Cognitive status was the only condition taken into account as co-variable (n = 3) or stratifying variable (n = 1) and was used as outcome measure in seven studies.Conclusions: We conclude that geriatric characteristics are rarely taken into account in RCTs on antidepressant drugs in late-life depression, and studies including the oldest adults are underrepresented. This warrants recruitment of the oldest adults and adjustment of treatment strategies in future studies. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Sedentary behaviour may increase the risk of dementia. Studying physiological effects of sedentary behaviour on cerebral health may provide new insights into the nature of this association. Accordingly, we reviewed if and how acute and habitual sedentary behaviour relate to brain health factors in middle-aged and older adults (≥45 years). Four databases were searched. Twenty-nine studies were included, with mainly cross-sectional designs. Nine studies examined neurotrophic factors and six studied functional brain measures, with the majority of these studies finding no associations with sedentary behaviour. The results from studies on sedentary behaviour and cerebrovascular measures were inconclusive. There was a tentative association between habitual sedentary behaviour and structural white matter health. An explanatory pathway for this effect might relate to the immediate vascular effects of sitting, such as elevation of blood pressure. Nevertheless, due to the foremost cross-sectional nature of the available evidence, reverse causality could also be a possible explanation. More prospective studies are needed to understand the potential of sedentary behaviour as a target for brain health. • Sedentary behaviour is not associated with neurotrophic factors. • During prolonged sitting acute changes are seen on cerebrovascular measures. • Sedentary behaviour seems particularly associated with reduced white matter health. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the use of cerebrospinal fluid as a biomarker in Alzheimer's disease.

Objectives Understanding which persons most likely use particular combinations of service types is important as this could lead to a better understanding of care pathways. The aim of this study is to identify combinations of service use within a sample of community-dwelling people with mild cognitive impairment (MCI) and dementia and identify factors related to these service use combinations. Methods A latent class analysis performed at baseline on a merged dataset (n = 530) was used to classify care recipients based on following service use types: general practitioner visits, physiotherapist visits, hospital outpatient specialist visits, emergency room visits, hospital inpatient visits with stay over, day care visits, use of domestic homecare, use of personal homecare, and informal care on (instrumental) activities of daily living. Multinomial logistic regression was performed to identify factors associated with service use combinations using clinical characteristics of the care recipient and demographic characteristics of the care recipient and caregiver. Results Three service use classes were identified; a formal homecare class (10% of participants), an informal care class (46% of participants), and a low user class (44% of participants). Factors increasing the likelihood of being in the formal homecare class compared with the low service use class included a diagnosis of MCI or dementia, activities of daily living impairment, older age of the care recipient, and care recipient not living together with the caregiver. Conclusions Besides a diagnosis of MCI or dementia, other factors (activities of daily living impairment, age, and living situation) were associated with service use. We recommend using these factors alongside the diagnostic label for care indication. [ABSTRACT FROM AUTHOR]

Objective: Shared decision-making (SDM) is widely recommended as a way to support patients in making healthcare choices. Due to an ageing population, the number of older patients will increase. Existing models for SDM are not sufficient for this patient group, due to their multi-morbidity, the lack of guidelines and evidence applicable to the numerous combinations of diseases. The aim of this study was to gain consensus on a model for SDM in frail older patients with multiple morbidities.Methods: We used a three-round Delphi study to reach consensus on a model for SDM in older patients with multiple morbidities. The expert panel consisted of 16 patients (round 1), and 59 professionals (rounds 1-3). In round 1, the SDM model was introduced, rounds 2 and 3 were used to validate the importance and feasibility of the SDM model.Results: Consensus for the proposed SDM model as a whole was achieved for both importance (91% panel agreement) and feasibility (76% panel agreement).Conclusions: SDM in older patients with multiple morbidities is a dynamic process. It requires a continuous counselling dialogue between professional and patient or proxy decision maker.Practice Implications: The developed model for SDM in clinical practice may help professionals to apply SDM in the complex situation of the care for older patients. [ABSTRACT FROM AUTHOR]

We investigated the impact of the colour of football outfits on localising football players and on the results of football matches. Two studies were conducted: an experimental study examining the effects of outfit colour on the assessment of the positions of computer-animated football players in a video set-up (study 1) and a retrospective study on professional football clubs’ performances dependent on their outfit colours (study 2). The studies were conducted with 18 human volunteers aged 15–18 years (study 1) and league results from 10 professional European football teams over 17 years (1995–2013) (study 2). We analysed the number of correct assessments of the positions of virtual football players with different outfit colours (study 1) and analysed the relationship between match results and outfits’ colours (study 2). Study 1 showed that the position of players wearing white outfits was better assessed in 5.2% of the trials compared to players wearing green outfits (P = 0.007). Study 2 showed that Manchester City conceded less goals against in away games in highly visible kits (r = 0.62;P = 0.024), while Newcastle United conceded less goals and won more points while playing in kits associated with low visibility (r = 0.63;P = 0.007;r = 0.50;P = 0.040, respectively). We conclude that the colour of football outfits affects evaluations of football players’ positions on the field, with white tricots resulting in the best location assessment. The outfit colour may indirectly influence football match results, warranting more attention to the home and away shirts by team managers and football scientists. [ABSTRACT FROM AUTHOR]

Objectives To develop a questionnaire, the Geriatric In-hospital Nursing Care Questionnaire (Ger INCQ), to measure, in an integrated way, the care that older adults receive in the hospital and nurses' attitudes toward and perceptions about caring for older adults. Design Questionnaire development. Setting Twelve university and teaching hospitals. Participants Thirteen experienced geriatric nurses and three geriatricians from 12 hospitals evaluated an initial version of the questionnaire. Two hundred seventy-one nurses, primarily registered nurses from 11 geriatric, medical, and surgical departments in six hospitals, validated the final questionnaire. Measurements Items from two published instruments were extracted for use in the questionnaire. Content validity was confirmed using the Delphi technique with an expert panel. Internal consistency was measured by calculating Cronbach alpha; intrarater reliability was measured using test-retest correlations and intraclass correlation coefficients ( ICCs); differences between hospital departments were analyzed using analysis of variance. Sensitivity to detect before-and-after changes with implementation of a geriatric care program was determined using the Student t-test. Results Consensus was reached after three Delphi rounds. The Ger INCQ is a self-administered questionnaire to be filled out by hospital nurses that comprises five subscales with 67 items. It has good content validity (each item content validity index >0.9) and good internal consistency (Cronbach alpha = 0.86). Intrarater reliability revealed high test-retest results ( ICC = 0.87). The questionnaire detected significant differences between nurses in three types of hospital departments (medical, surgical, and geriatric ( P < .01). The Ger INCQ was sensitive to changes after an educational program ( P < .02) and had a large effect size (0.5). Conclusion The Ger INCQ is a reliable and valid tool and is sensitive to change over time. It is clinically relevant because it provides a quantitative measure of hospital nurses' geriatric practices, attitudes, and perceptions. Moreover, the Ger INCQ is suitable for monitoring progress after implementation of geriatric improvement programs. [ABSTRACT FROM AUTHOR]

Co-morbidity and frailty are common in Alzheimer's disease (AD) and may contribute to the heterogeneity in clinical manifestations of the disease. We cross-sectionally investigated whether co-morbidity and frailty were independently associated with the clinical manifestation of AD in the 4C-Dementia study; a multicenter, longitudinal study in newly diagnosed AD patients. Clinical manifestation was operationalized using a composite of cognitive performance (neuropsychological assessment), activities of daily living (Disability Assessment for Dementia; DAD) and neuropsychiatric symptoms (Neuropsychiatric Inventory). As predictors of prime interest, co-morbidity was determined using the Cumulative Illness Rating Scale (CIRS-G) and frailty by the Fried criteria. In total, 213 AD patients participated (mean age 75 ± 10 years; 58% females). In linear regression models adjusted for age, gender, education, and disease duration, CIRS-G (β = -0.21, p < 0.01) and frailty (β = -0.34, p < 0.001) were separately associated with clinical AD manifestation. However, CIRS-G (β = -0.12, p = 0.12) lost statistical significance when both were combined (frailty: β = -0.31, p < 0.001). Models with the individual components of clinical AD manifestation as dependent variables show significant associations between cognitive performance and CIRS-G (β = -0.22, p = 0.01), and between DAD and frailty (β = -0.37, p < 0.001). Our findings indicate that physical health and clinical AD manifestation are associated. This association may be responsible for part of the heterogeneity in the presentation of AD. This emphasizes the importance of adequate assessment of co-morbid medical conditions and frailty in patients with AD. [ABSTRACT FROM AUTHOR]

Background: Until now, multiple reviews on the pharmacological treatment of dementia have been published. Methods: We performed a scoping review to summarize research findings and to identify gaps in the existing literature. We searched the literature and assessed the risk of bias of the included reviews. A team of clinical experts assessed the fields in which more research is necessary. Fifty-five reviews with a low risk of bias were included, most of them concerning the treatment of cognitive decline (n = 16) and behavioral symptoms (n = 10) in Alzheimer's disease (AD). For cognitive impairment, cholinesterase inhibitors (n = 13) and memantine (n = 7) were described most frequently. Little information was found about the treatment of depression in dementia. Conclusions: For many current treatments, there is sufficient evidence. New research should focus on the symptomatic treatment of the earliest and most salient complaints in AD as well as on disease-modifying interventions acting at the level of the amyloid cascade. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: To identify prodromal Alzheimer's disease (AD) subjects using a data-driven approach to determine cognitive profiles in mild cognitive impairment (MCI). Methods: A total of 881 MCI subjects were recruited from 20 memory clinics and followed for up to 5 years. Outcome measures included cognitive variables, conversion to AD, and biomarkers (e.g. CSF, and MRI markers). Two hierarchical cluster analyses (HCA) were performed to identify clusters of subjects with distinct cognitive profiles. The first HCA included all subjects with complete cognitive data, whereas the second one selected subjects with very mild MCI (MMSE ≥28). ANOVAs and ANCOVAs were computed to examine whether the clusters differed with regard to conversion to AD, and to AD-specific biomarkers. Results: The HCAs identified 4-cluster solutions that best reflected the sample structure. One cluster (aMCIsingle) had a significantly higher conversion rate (19%), compared to subjective cognitive impairment (SCI, p < 0.0001), and non-amnestic MCI (naMCI, p = 0.012). This cluster was the only one showing a significantly different biomarker profile (Aβ42, t-tau, APOE ε4, and medial temporal atrophy), compared to SCI or naMCI. Conclusion: In subjects with mild MCI, the single-domain amnestic MCI profile was associated with the highest risk of conversion, even if memory impairment did not necessarily cross specific cut-off points. A cognitive profile characterized by isolated memory deficits may be sufficient to warrant applying prevention strategies in MCI, whether or not memory performance lies below specific z-scores. This is supported by our preliminary biomarker analyses. However, further analyses with bigger samples are needed to corroborate these findings. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]