Associations Between Nutrient Intake and Corresponding Nutritional Biomarker Levels in Blood in a Memory Clinic Cohort:The NUDAD Project

Diet is a promising intervention target to prevent or slow Alzheimer's disease (AD). Early (predementia) stages of AD offer a unique opportunity for dietary interventions. Nutritional assessment methods to estimate nutrient intake have, however, not been validated in clinical populations. Hence, we assessed the association between nutrient intake assessed by food frequency questionnaire (FFQ) and nutrient status measured by nutritional biomarkers in blood in a clinical sample of controls, mild cognitive impairment (MCI), and patients with AD

Social cognition deficits and biometric signatures in the behavioural variant of Alzheimer’s disease

The behavioural variant of Alzheimer’s disease (bvAD) is characterized by early predominant behavioural changes, mimicking the behavioural variant of frontotemporal dementia (bvFTD), which is characterized by social cognition deficits and altered biometric responses to socioemotional cues. These functions remain understudied in bvAD. We investigated multiple social cognition components (i.e. emotion recognition, empathy, social norms and moral reasoning), using the Ekman 60 faces test, Interpersonal Reactivity Index, empathy eliciting videos, Social Norms Questionnaire and moral dilemmas, while measuring eye movements and galvanic skin response. We compared 12 patients with bvAD with patients with bvFTD (n = 14), typical Alzheimer’s disease (tAD, n = 13) and individuals with subjective cognitive decline (SCD, n = 13), using ANCOVAs and age- and sex-adjusted post hoc testing. Patients with bvAD (40.1 ± 8.6) showed lower scores on the Ekman 60 faces test compared to individuals with SCD (49.7 ± 5.0, P &lt; 0.001), and patients with tAD (46.2 ± 5.3, P = 0.05) and higher scores compared to patients with bvFTD (32.4 ± 7.3, P = 0.002). Eye-tracking during the Ekman 60 faces test revealed no differences in dwell time on the eyes (all P &gt; 0.05), but patients with bvAD (18.7 ± 9.5%) and bvFTD (19.4 ± 14.3%) spent significantly less dwell time on the mouth than individuals with SCD (30.7 ± 11.6%, P &lt; 0.01) and patients with tAD (32.7 ± 12.1%, P &lt; 0.01). Patients with bvAD (11.3 ± 4.6) exhibited lower scores on the Interpersonal Reactivity Index compared with individuals with SCD (15.6 ± 3.1, P = 0.05) and similar scores to patients with bvFTD (8.7 ± 5.6, P = 0.19) and tAD (13.0 ± 3.2, P = 0.43). The galvanic skin response to empathy eliciting videos did not differ between groups (all P &gt; 0.05). Patients with bvAD (16.0 ± 1.6) and bvFTD (15.2 ± 2.2) showed lower scores on the Social Norms Questionnaire than patients with tAD (17.8 ± 2.1, P &lt; 0.05) and individuals with SCD (18.3 ± 1.4, P &lt; 0.05). No group differences were observed in scores on moral dilemmas (all P &gt; 0.05), while only patients with bvFTD (0.9 ± 1.1) showed a lower galvanic skin response during personal dilemmas compared with SCD (3.4 ± 3.3 peaks per min, P = 0.01). Concluding, patients with bvAD showed a similar although milder social cognition profile and a similar eye-tracking signature to patients with bvFTD and greater social cognition impairments and divergent eye movement patterns compared with patients with tAD. Our results suggest reduced attention to salient facial features in these phenotypes, potentially contributing to their emotion recognition deficits.</p

A caregiver's perspective on clinically relevant symptoms in behavioural variant frontotemporal dementia: tools for disease management and trial design

Background: Adequate detection of symptoms and disease progression in behavioural variant frontotemporal dementia (bvFTD) is complex. Dementia cohorts usually utilize cognitive and functional measures, which fail to detect dominant behavioural and social cognitive deficits in bvFTD. Moreover, since patients typically have a loss of insight, caregivers are important informants. This is the first qualitative study to investigate caregiver relevant symptoms during the disease course of bvFTD, aiming to improve tools for diagnosis, progression, and future clinical trials. Methods: Informal caregivers of patients in different disease stages of bvFTD (N = 20) were recruited from the neurology outpatient clinic of the Amsterdam UMC and a patient organization for peer support in the Netherlands. Their perspectives on clinical relevance were thoroughly explored during individual semi-structured interviews. Inductive content analysis with open coding was performed by two researchers independently to establish overarching themes and patterns. Results: Caregivers reported a variety of symptoms, in which (i) loss of emotional connection, (ii) preoccupation and restlessness, and (iii) apathy and dependency compose major themes of relevance for diagnosis and treatment. Within heterogeneous disease trajectories, symptom presence differed between stages and among individuals, which is relevant in the context of progression and outcome measures. Significant socio-emotional changes dominated in early stages, while severe cognitive, behavioural, and physical deterioration shifted focus from predominant personality change to quality of life in later stages. Conclusions: Caregiver perspectives on target symptoms in bvFTD differ according to clinical stage and patient-caregiver characteristics, with significant socio-emotional changes characterizing early stages. These findings call for more appropriate tools and symptomatic treatments, as well as a personalized approach in treatment of bvFTD and a focus on early stage interventions in clinical trial design

A suboptimal diet is associated with poorer cognition: The NUDAD project

Nutrition is one of the modifiable risk factors for cognitive decline and Alzheimer’s disease (AD) dementia, and is therefore highly relevant in the context of prevention. However, knowledge of dietary quality in clinical populations on the spectrum of AD dementia is lacking, therefore we studied the association between dietary quality and cognitive impairment in Alzheimer’s disease (AD) dementia, mild cognitive impairment (MCI) and controls. We included 357 participants from the NUDAD project (134 AD dementia, 90 MCI, 133 controls). We assessed adherence to dietary guidelines (components: vegetables, fruit, fibers, fish, saturated fat, trans‐fat, salt, and alcohol), and cognitive performance (domains: memory, language, visuospatial functioning, attention, and executive functioning). In the total population, linear regression analyses showed a lower vegetable intake is associated with poorer global cognition, visuospatial functioning, attention and executive functioning. In AD dementia, lower total adherence to dietary guidelines and higher alcohol intake were associated with poorer memory, a lower vegetable intake with poorer global cognition and executive functioning, and a higher trans‐fat intake with poorer executive functioning. In conclusion, a suboptimal diet is associated with more severely impaired cognition—this association is mostly attributable to a lower vegetable intake and is most pronounced in AD dementia.</p

Associations of AD biomarkers and cognitive performance with nutritional status: The NUDAD project

As malnutrition is common in patients with Alzheimer’s disease (AD), we evaluated nutritional status and body composition of patients with AD, mild cognitive impairment (MCI) and controls, and studied associations of AD biomarkers and cognitive performance with nutritional status and body composition. We included 552 participants, of which 198 patients had AD, 135 patients had MCI and 219 controls. We assessed nutritional status (mini nutritional assessment (MNA)) and body composition (body mass index (BMI), fat-free mass (FFM) and waist circumference). Linear regression analyses (adjusted for age, gender and education where appropriate) were applied to test associations of AD biomarkers and cognitive performance on five domains with nutritional parameters (dependent). Patients with MCI and AD had a lower BMI and MNA score than controls. Worse performance in all cognitive domains was associated with lower MNA score, but not with body composition. AD biomarkers were associated with MNA score, BMI and waist circumference, and associations with MNA score remained after adjustment for cognitive performance. Both AD biomarkers and cognitive performance were associated with nutritional status, associations with AD biomarkers remained after adjustment for cognition. Our data suggest that malnutrition is not only related to impaired cognition but also to AD pathology.</p