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.

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.

Neurofilament light level correlates with brain atrophy, and cognitive and motor performance.

Background: The usefulness of neurofilament light (NfL) as a biomarker for small vessel disease has not been established. We examined the relationship between NfL, neuroimaging changes, and clinical findings in subjects with varying degrees of white matter hyperintensity (WMH). Methods: A subgroup of participants (n = 35) in the Helsinki Small Vessel Disease Study underwent an analysis of NfL in cerebrospinal fluid (CSF) as well as brain magnetic resonance imaging (MRI) and neuropsychological and motor performance assessments. WMH and structural brain volumes were obtained with automatic segmentation. Results: CSF NfL did not correlate significantly with total WMH volume (r = 0.278, p = 0.105). However, strong correlations were observed between CSF NfL and volumes of cerebral grey matter (r = -0.569, p < 0.001), cerebral cortex (r = -0.563, p < 0.001), and hippocampi (r = -0.492, p = 0.003). CSF NfL also correlated with composite measures of global cognition (r = -0.403, p = 0.016), executive functions (r = -0.402, p = 0.017), memory (r = -0.463, p = 0.005), and processing speed (r = -0.386, p = 0.022). Regarding motor performance, CSF NfL was correlated with Timed Up and Go (TUG) test (r = 0.531, p = 0.001), and gait speed (r = -0.450, p = 0.007), but not with single-leg stance. After adjusting for age, associations with volumes in MRI, functional mobility (TUG), and gait speed remained significant, whereas associations with cognitive performance attenuated below the significance level despite medium to large effect sizes. Conclusion: NfL was strongly related to global gray matter and hippocampal atrophy, but not to WMH severity. NfL was also associated with motor performance. Our results suggest that NfL is independently associated with brain atrophy and functional mobility, but is not a reliable marker for cerebral small vessel disease.

Dietary Intake of Flavonoids and Ventilatory Function in European Adults: A GA²LEN Study.

BACKGROUND: Flavonoids exert anti-inflammatory properties and modulate oxidative stress in vitro, suggesting a protective effect on lung function, but epidemiological studies examining this association are scarce. METHODS: A stratified random sample was drawn from the GA²LEN screening survey, in which 55,000 adults aged 15 to 75 answered a questionnaire on respiratory symptoms. Post-bronchodilator spirometry was obtained from 2850 subjects. Forced vital capacity (FVC), the ratio between the forced exhaled volume in 1 second (FEV1) and FVC (FEV1/FVC), FVC below lower limit of normal (FVC < LLN), and FEV1/FVC < LLN were calculated. Intake of the six main subclasses of flavonoids was estimated using the GA²LEN Food Frequency Questionnaire. Adjusted associations between outcomes and each subclass of flavonoids were examined with multivariate regressions. Simes' procedure was used to test for multiple comparisons. RESULTS: A total of 2599 subjects had valid lung function and dietary data. A lower prevalence of FVC < LLN (airway restriction) was observed in those with higher total flavonoid (adjusted odds ratio (aOR), higher vs. lowest quintile intake 0.58; 95% Confidence Interval (CI) 0.36, 0.94), and pro-anthocyanidin intakes (aOR 0.47; 95% CI 0.27, 0.81). A higher FEV1/FVC was associated with higher intakes of total flavonoids and pro-anthocyanidins (adjusted correlation coefficient (a ß-coeff 0.33; 0.10, 0.57 and a ß-coeff 0.44; 95% CI 0.19, 0.69, respectively). After Simes' procedure, the statistical significance of each of these associations was attenuated but remained below 0.05, with the exception of total flavonoids and airway restriction. CONCLUSIONS: This population-based study in European adults provides cross-sectional evidence of a positive association of total flavonoid intake and pro-anthocyanidins and ventilatory function, and a negative association with spirometric restriction in European adults.

Is fruit and vegetable intake associated with asthma or chronic rhino-sinusitis in European adults? Results from the Global Allergy and Asthma Network of Excellence (GA2LEN) Survey.

BACKGROUND: Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases. OBJECTIVE: We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults. METHODS: A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GA2LEN) screening survey, in which 55,000 adults aged 15-75 answered a questionnaire on respiratory symptoms. Asthma score (derived from self-reported asthma symptoms) and CRS were the outcomes of interest. Dietary intake of 22 subgroups of fruits and vegetables was ascertained using the internationally validated GA2LEN Food Frequency Questionnaire. Adjusted associations were examined with negative binomial and multiple regressions. Simes procedure was used to control for multiple testing. RESULTS: A total of 3206 individuals had valid data on asthma and dietary exposures of interest. 22.8% reported having at least 1 asthma symptom (asthma score ≥1), whilst 19.5% had CRS. After adjustment for potential confounders, asthma score was negatively associated with intake of dried fruits (ß-coefficient -2.34; 95% confidence interval [CI] -4.09, -0.59), whilst CRS was statistically negatively associated with total intake of fruits (OR 0.73; 95% CI 0.55, 0.97). Conversely, a positive association was observed between asthma score and alliums vegetables (adjusted ß-coefficient 0.23; 95% CI 0.06, 0.40). None of these associations remained statistically significant after controlling for multiple testing. CONCLUSION AND CLINICAL RELEVANCE: There was no consistent evidence for an association of asthma or CRS with fruit and vegetable intake in this representative sample of European adults.

Regulation of brain activity in the fusiform face and parahippocampal place areas in 7-11-year-old children.

Developmental studies have demonstrated that cognitive processes such as attention, suppression of interference and memory develop throughout childhood and adolescence. However, little is currently known about the development of top-down control mechanisms and their influence on cognitive performance. In the present study, we used functional magnetic resonance imaging to investigate modulation of activity in the ventral visual cortex in healthy 7-11-year-old children and young adults. The participants performed tasks that required attention to either face (Fs task) or scene (Sf task) images while trying to ignore distracting scene or face images, respectively. A face-selective area in the fusiform gyrus (fusiform face area, FFA) and an area responding preferentially to scene images in the parahippocampal gyrus (parahippocampal place area, PPA) were defined using functional localizers. Children responded slower and less accurately in the tasks than adults. In children, the right FFA was less selective to face images and regulation of activity between the Fs and Sf tasks was weaker compared to adults. In the PPA, selectivity to scenes and regulation of activity, there according to the task demands were comparable between children and adults. During the tasks, children activated prefrontal cortical areas including the middle (MFG) and superior (SFG) frontal gyrus more than adults. Functional connectivity between the right FFA and left MFG was stronger in adults than children in the Fs task. Children, on the other hand, had stronger functional connectivity than adults in the Sf task between the right FFA and right PPA and between right MFG and medial SFG. There were no group differences in the functional connectivity between the PPA and the prefrontal cortex (PFC). Together the results suggest that, in 7-11-year-old children, the FFA is still immature, whereas the selectivity to scenes and regulation of activity in the PPA is comparable to adults. The results also indicated functional immaturity of the PFC in children compared to adults and weaker connectivity between the PFC and the rFFA, explaining the weaker regulation of activity in the rFFA between the Fs and Sf tasks.