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Aims Cardiovascular disease (CVD) has been suggested to accelerate cognitive decline and to be a risk factor for dementia, but still little is known about the cognitive course after a first cardiovascular event. Therefore, the present study aims to investigate the cognitive trajectories in both prevalent and incident CVD over a 12-year time period in the general population. Methods and results Cognitively healthy participants (age 24–82 years, n  = 1823) of a prospective cohort study were serially assessed at baseline, 6 and 12 years. Verbal memory, executive function, and information processing speed were analysed in adults with prevalent, incident, and no CVD. Random effects models were used to test the association between CVD and change in cognitive function over time. At baseline, participants with prevalent CVD showed more decline in memory and information processing speed than healthy controls. Participants with incident CVD also showed more decline in these cognitive domains, but this was only significant in the follow-up period from 6 to 12 years. Associations were more pronounced in participants aged younger than 65 years at baseline, and in sub-analyses with angina pectoris or myocardial infarction as the most prevalent CVD conditions. Conclusion Prevalent and incident CVD predict cognitive decline in middle-aged individuals. Findings for incident CVD suggest that the onset of decline is linked in time with the vascular event itself. Timely CVD management may delay the onset of decline. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is biologically heterogeneous, and detailed understanding of the processes involved in patients is critical for development of treatments. CSF contains hundreds of proteins, with concentrations reflecting ongoing (patho)physiological processes. This provides the opportunity to study many biological processes at the same time in patients. We studied whether Alzheimer's disease biological subtypes can be detected in CSF proteomics using the dual clustering technique non-negative matrix factorization. In two independent cohorts (EMIF-AD MBD and ADNI) we found that 705 (77% of 911 tested) proteins differed between Alzheimer's disease (defined as having abnormal amyloid, n = 425) and controls (defined as having normal CSF amyloid and tau and normal cognition, n = 127). Using these proteins for data-driven clustering, we identified three robust pathophysiological Alzheimer's disease subtypes within each cohort showing (i) hyperplasticity and increased BACE1 levels; (ii) innate immune activation; and (iii) blood-brain barrier dysfunction with low BACE1 levels. In both cohorts, the majority of individuals were labelled as having subtype 1 (80, 36% in EMIF-AD MBD; 117, 59% in ADNI), 71 (32%) in EMIF-AD MBD and 41 (21%) in ADNI were labelled as subtype 2, and 72 (32%) in EMIF-AD MBD and 39 (20%) individuals in ADNI were labelled as subtype 3. Genetic analyses showed that all subtypes had an excess of genetic risk for Alzheimer's disease (all P > 0.01). Additional pathological comparisons that were available for a subset in ADNI suggested that subtypes showed similar severity of Alzheimer's disease pathology, and did not differ in the frequencies of co-pathologies, providing further support that found subtypes truly reflect Alzheimer's disease heterogeneity. Compared to controls, all non-demented Alzheimer's disease individuals had increased risk of showing clinical progression (all P < 0.01). Compared to subtype 1, subtype 2 showed faster clinical progression after correcting for age, sex, level of education and tau levels (hazard ratio = 2.5; 95% confidence interval = 1.2, 5.1; P = 0.01), and subtype 3 at trend level (hazard ratio = 2.1; 95% confidence interval = 1.0, 4.4; P = 0.06). Together, these results demonstrate the value of CSF proteomics in studying the biological heterogeneity in Alzheimer's disease patients, and suggest that subtypes may require tailored therapy. [ABSTRACT FROM AUTHOR]

Background: Prospective studies in the general population show that slow gait speed is associated with cognitive decline and clinical progression to dementia. However, longitudinal studies in memory clinic populations are mostly lacking. We aimed to study the association between gait speed and grip strength and cognitive functioning at baseline and cognitive decline over time in memory clinic patients with subjective cognitive decline and mild cognitive impairment.Methods: We included 309 patients (age 70 ± 9 years, 108 [35%] women, Mini-Mental State Examination 27 ± 3 points). Baseline gait speed was assessed over 15 feet, grip strength with a hydraulic hand dynamometer. Cognitive functioning was assessed annually with a comprehensive test battery during 3 years.Results: Age- and gender-adjusted linear mixed models showed that slower gait speed was related to worse baseline attention, memory, information processing speed, and verbal fluency. Longitudinally, gait speed was related to decline in information processing speed and executive functioning. Weaker grip strength was related to worse baseline information processing speed and executive functioning but there were no longitudinal associations. Cox proportional hazards models revealed no significant associations with clinical progression.Conclusions: Our findings suggest that markers of physical performance are related to current cognitive status and modestly related to cognitive decline but are seemingly not useful as an early marker of incident clinical progression. [ABSTRACT FROM AUTHOR]

Subjects with Alzheimer's disease (AD) show impaired learning strategies. Whether impaired learning strategies are already present in subjects with prodromal AD remains unknown. The aim of the present study was to investigate the predictive accuracy of learning strategies for AD in subjects with Mild Cognitive Impairment (MCI). Subjects with MCI (n = 202) were selected from the Maastricht Memory Clinic. Subjects were reassessed over a period of 10 years. Fifty-five of the 202 subjects converted to AD. Learning strategies investigated were subjective organization and serial clustering. Lower scores of subjective organization were associated with a higher risk for AD (OR = 2.1, p = .002). Serial clustering did not predict AD. Prodromal AD is characterized by a decreased use of effortful learning strategies. This finding may have implications for the early detection of AD in MCI subjects and for the development of cognitive training programs. [ABSTRACT FROM PUBLISHER]

Background: spousal caregivers are usually of the same age as the dementia patient and therefore at risk of age-related cognitive decline. Suboptimal cognitive functioning in caregivers may have profound implications. Methods: fifty-four spousal caregivers of dementia patients from the Memory Clinic of the Academic Hospital Maastricht and the Regional Institute for Community Mental Health Care in the Netherlands were compared with 108 non-caregiving controls. Data were collected on patient and caregiver characteristics and caregiver cognitive functioning. Repeated measures statistical analyses were carried out to investigate the relationship between care giver cognitive functioning at baseline and patient behavioural problems and caregiver competence during 1 year of follow-up. Results: caregivers performed significantly worse on several cognitive domains compared with control subjects. Low performance on a verbal memory task was related to a decrease in caregiver subjective competence and an increase in patient hyperactivity. Conclusion: the results indicate that screening for cognitive impairment of spousal caregivers may be helpful, because suboptimal cognitive functioning may affect the ability to provide adequate care. [ABSTRACT FROM AUTHOR]

Background: transnational and psychometrically appropriate versions of instruments used in the diagnosis of dementia are essential for comparing information between different countries. The Cambridge Examination for Mental Disorders of the Elderly incorporates a brief neuropsychological test battery, Cambridge Cognitive Examination (recently revised version), which provides objective data on performance across a number of cognitive domains. Objective: to harmonise the Cambridge Cognitive Examination between seven European countries. Method: 40 patients with probable or possible Alzheimer' s disease of each of the seven countries were administered the Cambridge Cognitive Examination. The Nurse Observation Scale for Geriatrics was used to assess concordance between cognitive and behavioural measures. Results: only small differences between the various Cambridge Cognitive Examination versions were found, and patterns of correlation between Cambridge Cognitive Examination and the Nurse Observation Scale for Geriatrics were consistent. Conclusion: these findings indicate that the harmonisation of the Cambridge Cognitive Examination was successful. [ABSTRACT FROM AUTHOR]