Long-term cognitive and neurovascular changes after carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) has been associated with both cognitive decline and improvement, but the underlying neurovascular mechanisms are unclear. The aim of this study was to investigate the relationship between neurovascular indices and cognitive changes after CEA. METHODS: We studied 55 patients with severe (≥70%) symptomatic or asymptomatic carotid stenosis before and six months after CEA. A wide array of neuropsychological tests was arranged in eight cognitive domains and cognitive functions specific to hemisphere ipsilateral to operation. Differences in cognitive performance between patients and 38 matching healthy controls were studied with linear mixed models. Neurovascular functioning and microembolic signals were assessed with transcranial Doppler ultrasound of the middle cerebral artery. Associations between neurovascular indices and cognitive change were assessed with linear regression analyses. RESULTS: On group level, the CEA patients improved more than controls in working memory, whereas no cognitive deterioration was detected. Also on individual level, improvement was most frequently observed in working memory. Worse preoperative cerebrovascular reactivity was related with improvement in cognitive functions of the ipsilateral hemisphere. Low preoperative pulsatility index was associated with improvement in executive functioning and ipsilateral cognitive functions. Poorer preoperative blood flow velocity associated with improvement in complex attention. Microembolic signals were rare. CONCLUSION: The present findings suggest that CEA may have beneficial long-term effects on cognition. These effects may specifically involve patients with impaired preoperative circulatory adaptive mechanisms.

A Novel Computerized Flexible Attention Test in Detecting Executive Dysfunction of Patients with Early-Onset Cognitive Impairment and Dementia.

OBJECTIVE: The number of computer-based cognitive tests has increased in recent years, but there is a need for tests focusing on the assessment of executive function (EF), as it can be crucial for the identification of early-onset neurodegenerative disorders. This study aims to examine the ability of the Flexible Attention Test (FAT), a new computer-based test battery for detecting executive dysfunction of early-onset cognitive impairment and dementia patients. METHOD: We analyzed the FAT subtask results in memory clinic patients with cognitive symptom onset at ≤65 years. The patients were divided into four groups: early onset dementia (EOD, n = 48), mild cognitive impairment due to neurological causes (MCI-n, n = 34), MCI due to other causes (MCI-o, n = 99), and subjective cognitive decline (SCD, n = 14). The test accuracy to distinguish EOD patients from other groups was examined, as well as correlations with pen-and-paper EF tests. We also reported the 12-months follow-up results. RESULTS: The EOD and MCI-n patients performed significantly poorer (p ≤ .002) than those in the MCI-o and SCD groups in most of the FAT subtasks. The accuracies of the FAT subtasks to detect EOD from other causes were mainly moderate (0.34 ≤ area under the curve < 0.74). The FAT subtasks correlated logically with corresponding pen-and-paper EF tests (.15 ≤ r ≤ .75). No systematic learning effects were detected in the FAT performance at follow-up. CONCLUSIONS: The FAT appears to be a promising method for the precise evaluation of EF and applicable distinguishing early-onset neurodegenerative disorders from patients with other causes of cognitive problems.

Different Methods to Detect Stress in Knowledge Workers: A Pilot Study for Long-term Monitoring.

Stress is a common part of working life, but knowledge is lacking on how to identify it early and with little effort on the part of the employee. We investigated whether simple stress reports and computer usage data could be useful tools for long-term assessment of stress in real life. 38 experts responded to a baseline questionnaire on need for recovery (NFR) and psychological distress (General Health Questionnaire, GHQ12). Their computer usage for work was recorded for 5 months, during which they filled in a 4-month simple diary and a 2-week detailed diary on, for example, stress and productivity. Salivary cortisol and heart rate variability were collected on 3 consecutive days. Generalized estimating equations models were used for the analyses. High NFR and GHQ12 predicted self-reported stress during work, and a decrease in (some) mouse usage features, but not keyboard usage features, over the following months. Some mouse usage features were associated with stress and productivity. The results provide some support for the usefulness of simple stress questions and mouse usage features in assessing long-term stress in real life.

cCOG Web-Based Cognitive Assessment Tool.

Cognitive testing is an essential part of clinical diagnostics and clinical trials in Alzheimer's disease. Digital cognitive tests hold a great opportunity to provide more versatile and cost-efficient patient pathways through flexible testing including at home. In this work, we describe a web-based cognitive test, cCOG, that can be used in screening, differential diagnosis, and monitoring the progression of neurodegenerative diseases.

Neuropsychological Profiles, Etiologies, and Medical Comorbidities in Early-Onset Dementia and Cognitive Impairment: A Memory Outpatient Clinic Cohort Study.

Background: Although early-onset dementia (EOD) is associated with diagnostic challenges that differ from those of related to late-onset dementia, only limited studies have addressed the neuropsychological and health characteristics or specified the diagnoses underlying early-onset cognitive impairment in a real-world clinical setting. Objective: To investigate the neuropsychological profiles, etiologies, and comorbidities of an unselected cohort of memory clinic patients (≤65 years at symptom onset). Methods: The patients' (n = 210) diagnoses were determined based on comprehensive diagnostic workup. Medical comorbidities and neuropsychological profiles were compared between clinically relevant patient groups, namely early-onset dementia (n = 55), mild cognitive impairment due to vascular or suspected neurodegenerative (MCI-n, n = 35) or non-neurodegenerative (MCI-o, n = 106) etiologies, and subjective cognitive decline (n = 14). Results: The most prevalent diagnoses were Alzheimer's disease (AD, 14%) and depression (11%). Multiple prior medical conditions were common (67%); however, EOD patients had fewer other diagnoses (p = 0.008) than MCI-o patients. Compared to other groups, EOD patients had more severe deficits (p < 0.001) on immediate and delayed memory, processing speed, symptom awareness, and global cognition. AD patients had weaker memory retention ability but less behavioral symptoms than frontotemporal dementia (FTD) patients (p≤0.05). Depression was associated with better immediate memory, symptom awareness, and global cognition than AD and FTD (p < 0.05). Conclusions: EOD is associated with more severe and widespread neuropsychological deficits but fewer prior medical diagnoses than nondegenerative etiologies of cognitive impairment. AD and depression are common etiologies and the neuropsychological profiles are partly overlapping; however, memory, symptom awareness and global cognitive impairment measures may help in the differential diagnosis.

Utility of the INECO Frontal Screening and the Frontal Assessment Battery in detecting executive dysfunction in early-onset cognitive impairment and dementia.

OBJECTIVE: The INECO Frontal Screening (IFS) and the Frontal Assessment Battery (FAB) are executive dysfunction (ED) screening tools that can distinguish patients with neurodegenerative disorders from healthy controls and, to some extent, between dementia subtypes. This paper aims to examine the suitability of these tests in assessing early-onset cognitive impairment and dementia patients. METHOD: In a memory clinic patient cohort (age mean = 57.4 years) with symptom onset at ≤65 years, we analyzed the IFS and the FAB results of four groups: early-onset dementia (EOD, n = 49), mild cognitive impairment due to neurological causes (MCI-n, n = 34), MCI due to other causes such as depression (MCI-o, n = 99) and subjective cognitive decline (SCD, n = 14). Data were gathered at baseline and at 6 and 12 months. We also studied the tests' accuracy in distinguishing EOD from SCD patients and ED patients from those with intact executive functioning. Correlations with neuropsychological measures were also studied. RESULTS: The EOD group had significantly (p < .05) lower IFS and FAB total scores than the MCI-o and SCD groups. Compared with the FAB, the IFS showed more statistically significant (p < .05) differences between diagnostic groups, greater accuracy (IFS AUC = .80, FAB AUC = .75, p = .036) in detecting ED and marginally stronger correlations with neuropsychological measures. We found no statistically significant differences in the EOD group scores from baseline up to 6- or 12-months follow-up. CONCLUSIONS: While both tests can detect EOD among memory clinic patients, the IFS may be more reliable in detecting ED than the FAB.

Subjective vs informant-reported cognitive complaints have differential clinical significance in covert cerebral small vessel disease.

Objective: Subjective cognitive complaints are common in patients with cerebral small vessel disease (cSVD), yet their relationship with informant evaluations, objective cognitive functions and severity of brain changes are poorly understood. We studied the associations of subjective and informant reports with findings from comprehensive neuropsychological assessment and brain MRI. Method: In the Helsinki SVD Study, 152 older adults with varying degrees of white matter hyperintensities (WMH) but without stroke or dementia were classified as having normal cognition or mild cognitive impairment (MCI) based on neuropsychological criteria. The measures also included continuous domain scores for memory and executive functions. Cognitive complaints were evaluated with the subjective and informant versions of the Prospective and Retrospective Memory Questionnaire (PRMQ) and Dysexecutive Questionnaire (DEX); functional abilities with the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL); and depressive symptoms with the Geriatric Depression Scale (GDS-15). Results: Subjective cognitive complaints correlated significantly with informant reports (r=0.40-0.50, p<0.001). After controlling for demographics, subjective and informant DEX and PRMQ were not related to MCI, memory or executive functions. Instead, subjective DEX and PRMQ significantly associated with GDS-15 and informant DEX and PRMQ with WMH volume and A-IADL. Conclusions: Neither subjective nor informant-reported cognitive complaints associated with objective cognitive performance. Informant-evaluations were related to functional impairment and more severe WMH, whereas subjective complaints only associated with mild depressive symptoms. These findings suggest that awareness of cognitive impairment may be limited in early-stage cSVD and highlight the value of informant assessments in the identification of patients with functional impairment.

A FinnGen pilot clinical recall study for Alzheimer's disease.

Successful development of novel therapies requires that clinical trials are conducted in patient cohorts with the highest benefit-to-risk ratio. Population-based biobanks with comprehensive health and genetic data from large numbers of individuals hold promise to facilitate identification of trial participants, particularly when interventions need to start while symptoms are still mild, such as for Alzheimer's disease (AD). This study describes a process for clinical recall studies from FinnGen. We demonstrate the feasibility to systematically ascertain customized clinical data from FinnGen participants with ICD10 diagnosis of AD or mild cognitive disorder (MCD) in a single-center cross-sectional study testing blood-based biomarkers and cognitive functioning in-person, computer-based and remote. As a result, 19% (27/140) of a pre-specified FinnGen subcohort were successfully recalled and completed the study. Hospital records largely validated registry entries. For 8/12 MCD patients, other reasons than AD were identified as underlying diagnosis. Cognitive measures correlated across platforms, with highest consistencies for dementia screening (r = 0.818) and semantic fluency (r = 0.764), respectively, for in-person versus telephone-administered tests. Glial fibrillary acidic protein (GFAP) (p < 0.002) and phosphorylated-tau 181 (pTau-181) (p < 0.020) most reliably differentiated AD from MCD participants. We conclude that informative, customized clinical recall studies from FinnGen are feasible.

The Cognitive Function at Work Questionnaire in memory clinic setting: a validation study.

INTRODUCTION: As there is a trend toward more people seeking medical help due to cognitive symptoms, validated and targeted questionnaires are increasingly important in the clinical evaluation process. The Cognitive Function at Work Questionnaire (CFWQ) was developed to identify and rate subjective cognitive symptoms of individuals active in working life. However, its psychometric characteristics have not been previously studied in a memory clinic setting. METHOD: The factorial structure, internal consistency, test-retest reliability, and convergent validity of the CFWQ were studied in a memory clinic setting (N = 113). We also investigated the instrument's ability to identify cognitive symptoms in a cohort of early-onset dementia (EOD, N = 22), mild cognitive impairment-neurological (MCI-n, N = 18), MCI due to mood, sleep, or other physical health problems (MCI-o, N = 59), and subjective cognitive decline (SCD, N = 14) patients. RESULTS: Based on factor analysis, eight cognitive subscales were identified covering main cognitive domains: Memory, Language, Executive Function, Speed of Processing, Cognitive Control, Name Memory, Visuospatial/Praxis and Attention. The internal consistency (α = .93) and the test-retest reliability (ICC = .91) were high. Several correlations (r = .19 - .33, p < .05) were documented between neuropsychological impairment level and CFWQ scores. EOD, MCI-n, MCI-o, and SCD groups did not differ statistically significantly in the levels of cognitive symptoms as measured by the CFWQ Total score. EOD group scored higher (p = .009) than other patient groups on the Visuospatial/Praxis subscale, but the difference between EOD and MCI-o groups turned insignificant after correcting for multiple testing. CONCLUSIONS: The results of the study support the validity and reliability characteristics of the CFWQ in a memory clinic setting. The instrument is easy-to-use and has clinical utility in capturing the subjective cognitive symptoms of patients active in working life and who need a referral to a more detailed evaluation.

The Added Value of Remote Technology in Cardiac Rehabilitation on Physical Function, Anthropometrics, and Quality of Life: Cluster Randomized Controlled Trial.

BACKGROUND: Cardiovascular diseases (CVDs) cause most deaths globally and can reduce quality of life (QoL) of rehabilitees with cardiac disease. The risk factors of CVDs are physical inactivity and increased BMI. With physical activity, it is possible to prevent CVDs, improve QoL, and help maintain a healthy body mass. Current literature shows the possibilities of digitalization and advanced technology in supporting independent self-rehabilitation. However, the interpretation of the results is complicated owing to the studies' high heterogeneity. In addition, the added value of this technology has not been studied well, especially in cardiac rehabilitation. OBJECTIVE: We aimed to examine the effectiveness of added remote technology in cardiac rehabilitation on physical function, anthropometrics, and QoL in rehabilitees with CVD compared with conventional rehabilitation. METHODS: Rehabilitees were cluster randomized into 3 remote technology intervention groups (n=29) and 3 reference groups (n=30). The reference group received conventional cardiac rehabilitation, and the remote technology intervention group received conventional cardiac rehabilitation with added remote technology, namely, the Movendos mCoach app and Fitbit charge accelerometer. The 12 months of rehabilitation consisted of three 5-day in-rehabilitation periods in the rehabilitation center. Between these periods were two 6-month self-rehabilitation periods. Outcome measurements included the 6-minute walk test, body mass, BMI, waist circumference, and World Health Organization QoL-BREF questionnaire at baseline and at 6 and 12 months. Between-group differences were assessed using 2-tailed t tests and Mann-Whitney U test. Within-group differences were analyzed using a paired samples t test or Wilcoxon signed-rank test. RESULTS: Overall, 59 rehabilitees aged 41 to 66 years (mean age 60, SD 6 years; n=48, 81% men) were included in the study. Decrement in waist circumference (6 months: 1.6 cm; P=.04; 12 months: 3 cm; P<.001) and increment in self-assessed QoL were greater (environmental factors: 0.5; P=.02) in the remote technology intervention group than the reference group. Both groups achieved statistically significant improvements in the 6-minute walk test in both time frames (P=.01-.03). Additionally, the remote technology intervention group achieved statistically significant changes in the environmental domain at 0-6 months (P=.03) and waist circumference at both time frames (P=.01), and reference group achieve statistically significant changes in waist circumference at 0-6 months (P=.02). CONCLUSIONS: Remote cardiac rehabilitation added value to conventional cardiac rehabilitation in terms of waist circumference and QoL. The results were clinically small, but the findings suggest that adding remote technology to cardiac rehabilitation may increase beneficial health outcomes. There was some level of systematic error during rehabilitation intervention, and the sample size was relatively small. Therefore, care must be taken when generalizing the study results beyond the target population. To confirm assumptions of the added value of remote technology in rehabilitation interventions, more studies involving different rehabilitees with cardiac disease are required. TRIAL REGISTRATION: ISRCTN Registry ISRCTN61225589; https://www.isrctn.com/ISRCTN61225589.

FinnGen provides genetic insights from a well-phenotyped isolated population.

Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10-11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.

The Cognitive Function at Work Questionnaire (CFWQ): A new scale for measuring cognitive complaints in occupational population.

Cognitive functioning is a relevant work and health related topic, however, validated methods to assess subjective cognitive complaints (SCC) at work are lacking. We introduce the Cognitive Function at Work Questionnaire (CFWQ) for measuring SCC in occupational settings. 1-year follow-up data of 418 employees from a Finnish public media service company was analyzed. Participants completed web-based CFWQ, cognitive tests and a broad set of questionnaires for evaluating depression, anxiety, insomnia, daytime sleepiness, burnout, stress, mental job burden, work ability, cognitive errors, and perceived health. The factor analysis yielded a model with the CFWQ subdomains: Memory, Language, Executive Function, Speed of Processing, Cognitive Control and Name Memory. The internal consistency (Cronbach's alpha = .87) and the test-retest constancy (ICC = .84) reflected good reliability. Correlation between the CFWQ and cognitive errors at work ranged from .25 to .64 indicating adequate concurrent validity. Employees with depression, insomnia and burnout symptoms had higher (p < .001) CFWQ scores than participants without these symptoms. Depression and burnout symptom severity as well as accumulation of mood, sleep, and psychosocial stressors were associated with higher CFWQ scores (p < .001 in all). The CFWQ appears psychometrically sound measure for the assessment of SCC in occupational population.

Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

Economic evaluation of using polygenic risk score to guide risk screening and interventions for the prevention of type 2 diabetes in individuals with high overall baseline risk.

Type 2 diabetes (T2D) with increasing prevalence is a significant global public health challenge. Obesity, unhealthy diet, and low physical activity are one of the major determinants of the rise in T2D prevalence. In addition, family history and genetic risk of diabetes also play a role in the process of developing T2D. Therefore, solutions for the early identification of individuals at high risk for T2D for early targeted detection of T2D, prevention, and intervention are highly preferred. Recently, novel genomic-based polygenic risk scores (PRSs) have been suggested to improve the accuracy of risk prediction supporting the targeting of preventive interventions to those at highest risk for T2D. Therefore, the aim of the present study was to assess the cost-utility of an additional PRS testing information (as a part of overall risk assessment) followed by a lifestyle intervention and an additional medical therapy when estimated 10-year overall risk for T2D exceeded 20% among Finnish individuals screened as at the high-risk category (i.e., 10%-20% 10-year overall risk of T2D) based on traditional risk factors only. For a cost-utility analysis, an individual-level state-transition model with probabilistic sensitivity analysis was constructed. A 1-year cycle length and a lifetime time horizon were applied in the base-case. A 3% discount rate was used for costs and QALYs. Cost-effectiveness acceptability curve (CEAC) and estimates for the expected value of perfect information (EVPI) were calculated to assist decision makers. The use of the targeted PRS strategy reclassified 12.4 percentage points of individuals to be very high-risk individuals who would have been originally classified as high risk using the usual strategy only. Over a lifetime horizon, the targeted PRS was a dominant strategy (i.e., less costly, more effective). One-way and scenario sensitivity analyses showed that results remained dominant in almost all simulations. However, there is uncertainty, since the probability (EVPI) of cost-effectiveness at a WTP of 0€/QALY was 63.0% (243€) indicating the probability that the PRS strategy is a dominant option. In conclusion, the results demonstrated that the PRS provides moderate additional value in Finnish population in risk screening leading to potential cost savings and better quality of life when compared with the current screening methods for T2D risk.

Associations of Depressive Symptoms and Cognition in the FINGER Trial: A Secondary Analysis of a Randomised Clinical Trial.

Depression and cognition are associated, but the role of depressive symptoms in lifestyle interventions to prevent dementia needs further study. We investigated the intervention effect on depressive symptoms and their associations with cognition in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER; NCT01041989), a two-year multidomain lifestyle trial. One thousand two-hundred and sixty individuals (60-77 years) at risk for dementia were randomised into a multidomain intervention (diet, exercise, cognitive training, and vascular/metabolic risk monitoring) or control group (regular health advice). Depressive symptoms (Zung scale) and cognition (modified Neuropsychological Test Battery) were evaluated at baseline, 12, and 24 months. One thousand one-hundred and twenty-five participants had baseline Zung data. Mean Zung score decreased 0.73 (SD 5.6) points in the intervention and 0.36 (5.6) points in the control group, with nonsignificant between-group difference (group × time coefficient -0.006, 95% CI -0.019 to 0.007). Overall, higher baseline Zung score was associated with less improvement in global cognition (-0.140, p = 0.005) and memory (-0.231, p = 0.005). Participants with clinically significant baseline depressive symptoms (Zung ≥ 40 points) had less intervention benefit to executive functioning (group × time × Zung -0.096, 95% CI -0.163 to -0.028). Change in Zung score was not associated with change in cognition. Clinically significant depressive symptoms warrant more attention when designing dementia-prevention interventions.

Occupational complexity and cognition in the FINGER multidomain intervention trial.

INTRODUCTION: Lifetime exposure to occupational complexity is linked to late-life cognition, and may affect benefits of preventive interventions. METHODS: In the 2-year multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), we investigated, through post hoc analyses (N = 1026), the association of occupational complexity with cognition. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. RESULTS: Higher levels of occupational complexity were associated with better baseline cognition. Measures of occupational complexity had no association with intervention effects on cognition, except for occupational complexity with data, which was associated with the degree of intervention-related gains for executive function. DISCUSSION: In older adults at increased risk for dementia, higher occupational complexity is associated with better cognition. The cognitive benefit of the FINGER intervention did not vary significantly among participants with different levels of occupational complexity. These exploratory findings require further testing in larger studies.

The effect of adherence on cognition in a multidomain lifestyle intervention (FINGER).

INTRODUCTION: Lifestyle interventions may prevent cognitive decline, but the sufficient dose of intervention activities and lifestyle changes is unknown. We investigated how intervention adherence affects cognition in the FINGER trial (pre-specified subgroup analyses). METHODS: FINGER is a multicenter randomized controlled trial examining the efficacy of multidomain lifestyle intervention (ClinicalTrials.gov NCT01041989). A total of 1260 participants aged 60 to 77 with increased dementia risk were randomized to a lifestyle intervention and control groups. Percentage of completed intervention sessions, and change in multidomain lifestyle score (self-reported diet; physical, cognitive, and social activity; vascular risk) were examined in relation to change in Neuropsychological Test Battery (NTB) scores. RESULTS: Active participation was associated with better trajectories in NTB total and all cognitive subdomains. Improvement in lifestyle was associated with improvement in NTB total and executive function. DISCUSSION: Multidomain lifestyle changes are beneficial for cognitive functioning, but future interventions should be intensive enough, and supporting adherence is essential.

Synergistic associations of cognitive and motor impairments with functional outcome in covert cerebral small vessel disease.

BACKGROUND: Cognitive and motor impairments are the key clinical manifestations of cerebral small vessel disease (SVD), but their combined effects on functional outcome have not been elucidated. This study investigated the interactions and mediating effects of cognitive and motor functions on instrumental activities of daily living (IADL) and quality of life in older individuals with various degrees of white matter hyperintensities (WMH). METHODS: Participants of the Helsinki Small Vessel Disease Study (n = 152) were assessed according to an extensive clinical, physical, neuropsychological and MRI protocol. Volumes of WMH and gray matter (GM) were obtained with automated segmentation. RESULTS: Cognitive (global cognition, executive functions, processing speed, memory) and motor functions (gait speed, single-leg stance, timed up-and-go) had strong interrelations with each other, and they were significantly associated with IADL, quality of life as well as WMH and GM volumes. A consistent pattern on significant interactions between cognitive and motor functions was found on informant-evaluated IADL, but not on self-evaluated quality of life. The association of WMH volume with IADL was mediated by global cognition, whereas the association of GM volume with IADL was mediated by global cognition and timed up-and-go performance. CONCLUSION: The results highlight the complex interplay and synergism between motor and cognitive abilities on functional outcome in SVD. The combined effect of motor and cognitive disturbances on IADL is likely to be greater than their individual effects. Patients with both impairments are at disproportionate risk for poor outcome. WMH and brain atrophy contribute to disability through cognitive and motor impairment.