Comorbidity is less common in YO-AD than in LO-AD. However, general practitioners should be aware that approximately one-third of the patients with YO-AD suffer from or have endocrine, nutritional, and metabolic diseases and/or diseases of the circulatory system. Treatment should therefore not only focus on dementia but also on comorbidity. This attention may slow the functional decline in AD. These exploratory analyses suggested a higher prevalence of nervous system diseases in YO-AD compared with LO-AD. However, the finding did not reach statistical significance and in combination with the exploratory nature of the analyses justifies further investigation. If verified, this finding may help to decrease the time to diagnosis of AD and, subsequently, support in young patients with a neurological disease. Further investigation is needed to gain more insight into the association between comorbidity and AD in younger people.

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.

Our findings suggest that AD neuropathology in itself may be responsible for executive dysfunction. Potential explanations for these findings are discussed, focusing on the role of the hippocampus in executive function tests and reduced frontal-posterior connectivity in this patient sample.

BackgroundHeterogeneous disease trajectories of mild cognitive impairment (MCI) and dementia are frequently encountered in clinical practice, but there is still insufficient knowledge to understand the reasons and mechanisms causing this heterogeneity. In addition to correlates of the disorder, patient characteristics such as their health status, social environment, comorbidities and frailty may contribute to variability in trajectories over time. The current paper outlines the study design and the study population of and provides an overview of the data collected in the Clinical Course of Cognition and Comorbidity in Mild Cognitive Impairment (4C-MCI cohort, n = 315) and Dementia (4C-Dementia cohort, n = 331) Study. MethodsThe two complementary longitudinal cohorts part of the 4C study began enrolment in March 2010. Participants were prospectively recruited from three collaborating Dutch Alzheimer Centers, with three annual follow-up assessments after baseline. Extensive neuropsychological assessments, and detailed profiling of comorbidities, health and frailty at each follow up were the key features of the 4C study. As such, the 4C study was designed to study if and how patients’ comorbidities and frailty are associated with the course of MCI and dementia measured with a comprehensive and multidimensional set of outcomes including cognition, daily functioning, quality of life, behavioral disturbances, caregiver burden, institutionalization and death and whether the effects of medical health and frailty differ between MCI and dementia stages of cognitive disorders.ConclusionSampled in a clinical setting, the 4C study complements population-based studies on neurodegenerative disorders in terms of the type of assessment (e.g. comorbidity, frailty, and functional status were repeatedly assessed). The 4C study complements available clinical cohorts of MCI and dementia patients, because the exclusion criteria were kept to a minimum, to obtain a sample that is representative for the average patient visiting a memory clinic.

Objective: To identify determinants within 3 different domains (ie, somatic comorbidities, cognitive functioning, and neuropsychiatric symptoms [NPS]) of health-related quality of life (HRQoL) over time in memory clinic patients without dementia. Methods: This longitudinal multicenter cohort study with a 3-year observation period recruited 315 individuals (age: 69.8 ± 8.6, 64.4% males, Mini-Mental State Examination score 26.9 ± 2.6). A multivariable explanatory model was built using linear mixed effects models (forward selection per domain) to select determinants for self-perceived HRQoL over time, as measured by the EuroQoL-5D visual analogue scale (EQ VAS). Results: Mean HRQoL at study entry was 69.4 ± 15.6. The presence of agitation, appetite and eating abnormalities, and eyes/ears/nose (ie, sensory impairment) comorbidities were associated with a change in HRQoL over time. Agitation was most strongly associated with HRQoL over time. Conclusions: The association of somatic comorbidities and NPS in memory clinic patients with course of HRQoL shows that these should receive more awareness, detection, and monitoring by clinicians.