Adherence to Mediterranean diet is inversely associated with depressive symptoms in older women: findings from the NutBrain Study.

Data on the association of the Mediterranean diet (MD) with depressive symptoms in older people at high risk of depression are scarce. This study aimed to investigate the cross-sectional association of the adherence to the MD and its components with depressive symptoms in an Italian cohort of older men and women. A total of 325 men and 473 women aged 65­97 years (2019­2023) answered a 102-item semi-quantitative FFQ, which was used to calculate the Mediterranean diet score (MDS). Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale; subjects with a score of 16 or more were considered to have depression. Multivariable logistic regression was used for statistical analysis. The occurrence of depressive symptoms was 19·8 % (8·0 % men, 27·9 % women). High adherence to MDS (highest tertile) significantly reduced the odds of having depressive symptoms by 54·6 % (OR 0·454, 95 % CI 0·266, 0·776). In sex-stratified analysis, the reduction was evident in women (OR 0·385, 95 % CI 0·206, 0·719) but not in men (OR 0·828, 95 % CI 0·254, 2·705). Looking at the association of MDS components with depressive symptoms, we found an inverse significant association with fish consumption and the MUFA:SFA ratio above the median only in women (OR 0·444, 95 % CI 0·283, 0·697 and OR 0·579, 95 % CI 0·345, 0·971, respectively). High adherence to the MDS, and a high fish intake and MUFA:SFA ratio were associated with lower depressive symptoms in women only. Future longitudinal studies are needed to confirm these findings and to explore the underlying biological mechanisms.

Risk factors for post-COVID cognitive dysfunctions: the impact of psychosocial vulnerability.

BACKGROUND: Cognitive dysfunction is a well-established manifestation of the post-COVID syndrome. Psychological vulnerability to stressors can modify disease trajectories, causing long-term risk for negative outcomes. Nonetheless, how premorbid risk factors and response to stressor affect neuropsychological changes is still incompletely understood. In this study, we explored the impact of psychosocial variables on cognitive functioning in a post-COVID sample. METHODS: All subjects were submitted to a comprehensive neuropsychological battery and an assessment of perceived loneliness, post-traumatic stress, and changes in anxiety and depression levels. A social vulnerability index was also calculated. The set of psycho-social variables was reduced to two Principal Component Analysis (PCA) components: distress and isolation. RESULTS: Forty-five percent of individuals showed cognitive impairments, with predominant memory and executive deficits. Post-traumatic stress disorder was clinically relevant in 44% of the sample. Social vulnerability scores of the sample were comparable to those of general population. The individual performance in learning and response initiation/suppression was directly related to distress component, encasing anxiety, stress, and depression measures. CONCLUSION: These findings suggest that psychosocial assessment of post-COVID patients can detect fragile individuals at risk of cognitive impairments. Dedicated psychological support services may play a useful role in the prevention of post-COVID cognitive dysfunction.

A double-blind randomized controlled trial combining cognitive training (CoRe) and neurostimulation (tDCS) in the early stages of cognitive impairment.

BACKGROUND: The prevalence of neurodegenerative diseases is expected to increase over the next years, therefore, new methods able to prevent and delay cognitive decline are needed. AIMS: To evaluate the effectiveness of a combined treatment protocol associating a computerized cognitive training (CoRe) with anodal transcranial direct current stimulation (tDCS). METHODS: In this randomized controlled trial, 33 patients in the early stage of cognitive impairment were assigned to the experimental group (CoRE + real tDCS) or control group (CoRE + sham tDCS). In each group, the intervention lasted 3 consecutive weeks (4 sessions/week). A neuropsychological assessment was administered at baseline (T0), post-intervention (T1) and 6-months later (T2). RESULTS: The CoRE + real tDCS group only improved in working memory and attention/processing speed at both T1 and T2. It reported a stable MMSE score at T2, while the CoRE + sham tDCS group worsened. Age, mood, and T0 MMSE score resulted to play a role in predicting treatment effects. CONCLUSION: Combined multi-domain interventions may contribute to preventing or delaying disease progression. TRIAL REGISTRATION: Trial registration number (ClinicalTrials.gov): NCT04118686.

Evaluation of the efficacy of physical therapy on cognitive decline at 6-month follow-up in Parkinson disease patients with mild cognitive impairment: a randomized controlled trial.

BACKGROUND: In Parkinson's disease (PD), physical activity may represent a possible non-pharmacological intervention not only for improving motor symptoms but also for modulating cognitive impairment. AIMS: To evaluate the efficacy of an intensive physical program on cognitive functions in mid-stage PD patients with mild cognitive impairment (PD-MCI) over a 6-month follow-up. METHODS: This is a 6-month randomized controlled follow-up study. 40 PD-MCI patients were randomized to receive physical therapy (PT) or no specific intervention beside drug treatment (CT). Cognitive and motor assessments were performed at baseline (T0), 4 weeks after baseline (T1) and 6 months after T0. In a previous study, we reported a significant improvement in global cognitive functioning and attention/working-memory at T1. Here, we evaluated the residual effect of the training intervention at 6 months on both cognitive and motor performances. RESULTS: Intra-group analysis showed that at T2 most of cognitive and motor performances remained stable in the PT when compared to T0, while a significant worsening was observed in the CT. Between-group comparison at T2 showed significantly better results in PT than CT as regards MoCA and motor scales. The percentage change of cognitive and motor performances between T1 and T2 confirmed the benefit of physical therapy on global cognitive functioning scores (MMSE and MoCA). CONCLUSIONS: In this follow-up extension of a longitudinal randomized controlled study, we demonstrated that physical therapy has a positive effect on cognitive functions, which extends beyond the duration of the treatment itself to, at least temporarily, reducing cognitive decline. TRIAL REGISTRATION: Trial registration number (ClinicalTrials.gov): NCT04012086 (9th July 2019).

A double-blind randomized controlled trial of the efficacy of cognitive training delivered using two different methods in mild cognitive impairment in Parkinson's disease: preliminary report of benefits associated with the use of a computerized tool.

BACKGROUND: The effectiveness of computer-based cognitive training (CCT) remains controversial, especially in older adults with neurodegenerative diseases. AIMS: To evaluate the efficacy of CCT in patients with Parkinson's disease and mild cognitive impairment (PD-MCI). METHODS: In this randomized controlled trial, 53 patients were randomized to receive CCT delivered by means of CoRe software, traditional paper-and-pencil cognitive training (PCT), or an unstructured activity intervention (CG). In each group, the intervention lasted 3 consecutive weeks (4 individual face-to-face sessions/week). Neuropsychological assessment was administered at baseline (T0) and post-intervention (T1). Outcome measures at T0 and T1 were compared within and between groups. The Montreal Overall Cognitive Assessment (MoCA) was taken as the primary outcome measure. RESULTS: Unlike the PCT group and the CG, the patients receiving CCT showed significant medium/large effect size improvements in MoCA performance, global cognition, executive functions, and attention/processing speed. No baseline individual/demographic variables were associated with greater gains from the intervention, although a negative correlation with baseline MoCA performance was found. CONCLUSION: CCT proved effective in PD-MCI patients when compared with traditional PCT. Further follow-up assessments are being conducted to verify the retention of the gains and the potential ability of the tool to delay conversion to PD-dementia. Trial registration number (ClinicalTrials.gov): NCT04111640 (30th September 2019).

Exploring the relationship between Nutrition, gUT microbiota, and BRain AgINg in community-dwelling seniors: the Italian NutBrain population-based cohort study protocol.

BACKGROUND: Epidemiological evidence suggests that healthy diet is associated with a slowdown of cognitive decline leading to dementia, but the underlying mechanisms are still partially unexplored. Diet is the main determinant of gut microbiota composition, which in turn impacts on brain structures and functions, however to date no studies on this topic are available. The goal of the present paper is to describe the design and methodology of the NutBrain Study aimed at investigating the association of dietary habits with cognitive function and their role in modulating the gut microbiota composition, and brain measures as well. METHODS/DESIGN: This is a population-based cohort study of community-dwelling adults aged 65 years or more living in Northern Milan, Italy. At the point of presentation people are screened for cognitive functions. Socio-demographic characteristics along with lifestyles and dietary habits, medical history, drugs, functional status, and anthropometric measurements are also recorded. Individuals suspected to have cognitive impairment at the screening phase undergo a clinical evaluation including a neurological examination and a Magnetic Resonance Imaging (MRI) scanning (both structural and functional). Stool and blood samples for the gut microbiota analysis and for the evaluation of putative biological markers are also collected. For each subject with a confirmed diagnosis of Mild Cognitive Impairment (MCI), two cognitively intact controls of the same sex and age are visited. We intend to enrol at least 683 individuals for the screening phase and 240 persons for the clinical assessment. DISCUSSION: The NutBrain is an innovative study that incorporates modern and advanced technologies (i.e. microbiome and neuroimaging) into traditional epidemiologic design. The study represents a unique opportunity to address key questions about the role of modifiable risk factors on cognitive impairment, with a particular focus on dietary habits and their association with gut microbiota and markers of the brain-aging process. These findings will help to encourage and plan lifestyle interventions, for both prevention and treatment, aiming at promoting healthy cognitive ageing. TRIAL REGISTRATION: Trial registration number NCT04461951 , date of registration July 7, 2020 (retrospectively registered, ClinicalTrials.gov ).

Disease progression in relation to age at onset in a population with Alzheimer's Dementia.

One thousand and 679 Alzheimer's Disease patients (early onset EO: 152 and late onset LO: 1527) were evaluated after 12, 36 and 60 months. At baseline EO patients have higher Mini Mental State examination (MMSE) and fewer comorbidities in respect to LO group. The MMSE score did not significantly differ after 12, 36 and 60 months; a more marked worsening in instrumental daily activities was observed after 36 months in the EO compared with the LO group. These data allow to conclude that EO patients may have a slight faster progression in the disease within the first 3 years after the diagnosis, but in a longer follow-up no differences exist in respect to LO group. The literature failed to identify specific factors capable to influence the disease progression in AD. Our data are in substantial agreement with the literature and seem to confirm the great heterogeneity of AD patients.

Modeling Alzheimer Disease Through Functional Independence and Participation.

INTRODUCTION: The relationship between cognitive and functional impairment in Alzheimer Disease (AD) at the earliest stages of the disease is not well characterized. This study aimed at investigating such relationships along AD evolution by means of the Disability Assessment for Dementia (DAD). METHODS: Consecutive pairs of AD outpatients and their primary informal caregivers were enrolled. Patients were evaluated by means of the Mini Mental State Examination and neuropsychological tests. A clinician completed the Clinical Dementia Rating Scale to stage dementia severity and interviewed the caregivers to complete the Neuropsychiatric Inventory to assess behavioral disturbances and the DAD to evaluate patients' functional competence. RESULTS: A total of 158 dyads were enrolled; the Mini Mental State Examination score was used to stratify patients into 4 groups (>24; 20 to 23.9; 10 to 19.9; <10) that were compared. The statistical analysis revealed that all the cognitive domains were positively related to functional independence, but only logical and executive functions seemed to predict autonomy. An intergroup comparison did not show significant differences in the DAD subscales measuring initiation, planning and organization, and performance. The role of education emerged, confirming the relevance of cognitive reserve. DISCUSSION: As the field moves toward earlier intervention in preclinical AD, the detection of early functional changes may drive the definition of trials on prevention or intervention for dementia.

Correlations among age, cognitive impairment, and comorbidities in Alzheimer's disease: report from a center for cognitive disorders.

We report an update of our previous observations in Alzheimer's disease (AD) patients in the routine clinical practice considering in particular the interactions between age, concomitant pathologies, and treatment adherence. 2379 AD patients (M/F: 1058/1321, mean age: 74.1 ± 8.8) referred for a first visit to our center from September 2000 to April 2017. An increase of percentage of patients aged over 80 years along the years was confirmed (27% between September 2000 and December 2010, and 39% between January 2011 to April 2017). The patients over 80 years presented a Cumulative Illness Rating Scale (CIRS) significantly higher than patients under 80 years (p < 0.00001). Higher CIRS scores were associated with a lower treatment adherence (p < 0.0002) and greater cognitive impairment (p < 0.01). As people in advanced age with cognitive disorders will increase, our approach to dementing conditions has to change and fit to social and epidemiological modifications.

Quality of life in Alzheimer disease: a comparison of patients' and caregivers' points of view.

Unlike in other chronic diseases, the Quality of Life (QoL) of patients affected by Alzheimer Disease (AD) has not been well established, primarily because of the difficulties stemming from the study of patients with cognitive disorders. Because no cure is currently available for AD, the optimization of QoL represents the best possible outcome attainable in all stages of disease, making QoL assessment mandatory. This study identified variables related to patients' QoL and examined the agreement between patients' and caregivers' QoL ratings. A total of 135 dyads (patient and principal caregiver) were enrolled in the study. Patients' QoL evaluations showed a negative relationship with depressive mood and a positive relationship with Activities of Daily Living (ADL), whereas caregivers' QoL ratings showed a negative relationship with patients' depressive mood and behavioral disturbances. Caregivers tended to underestimate patients' QoL compared with the patients' own self-evaluations, with patients' dependency in performing ADL and behavioral disorders as well as caregivers' burdens and depression being the main factors associated with the discrepancy in these evaluations. These findings suggest that the use of proxies as a substitute for the self-report of QoL data should be treated with caution, always accounting for the presence of potential bias.

Investigating the individual and joint effects of socioeconomic status and lifestyle factors on mild cognitive impairment in older Italians living independently in the community: results from the NutBrain study.

OBJECTIVES: Despite extensive research, a clear understanding of the role of the interaction between lifestyle and socioeconomic status (SES) on cognitive health is still lacking. We investigated the joint association of socioeconomic factors in early to midlife and lifestyle in later life and Mild Cognitive Impairment (MCI). DESIGN: Observational cross-sectional study. SETTING: NutBrain study in northern Italy. PARTICIPANTS: 773 community-dwelling adults aged 65 years and older (73.2 ± 6.0 SD, 58.6% females) participating in the NutBrain study (2019-2023). MEASUREMENTS: Three SES indicators (home ownership, educational level, occupation) and five lifestyle factors (adherence to Mediterranean diet, physical activity, smoking habits, social network, leisure activities) were selected. Each factor was scored and summed to calculate SES and healthy lifestyle scores; their joint effect was also examined. The association with MCI was assessed by logistic regression controlling for potential confounders. Sex-stratified analysis was performed. RESULTS: In total, 24% of the subjects had MCI. The multivariable logistic model showed that a high SES and a high lifestyle score were associated with 81.8% (OR0.182; 95%CI 0.095-0.351), and 44.1% (OR0.559; 95%CI 0.323-0.968) lower odds of having MCI, respectively. When examining the joint effect of SES and lifestyle factors, the cognitive benefits of a healthy lifestyle were most pronounced in participants with low SES. A healthier lifestyle score was found to be significantly associated with lower odds of MCI, only in females. CONCLUSIONS: According to our findings, SES was positively associated with preserved cognitive function, highlighting the importance of active lifestyles in reducing socioeconomic health inequalities, particularly among those with a relatively low SES. TRIAL REGISTRATION: Trial registration number NCT04461951, date of registration July 7, 2020 (retrospectively registered, ClinicalTrials.gov).

Polypharmacy, drug-drug interactions, anticholinergic burden and cognitive outcomes: a snapshot from a community-dwelling sample of older men and women in northern Italy.

Polypharmacy (PP) use is very common in older people and may lead to drug-drug interactions (DDIs) and anticholinergic burden (ACB) that may affect cognitive function. We aimed to determine the occurrence of PP, potential DDIs and ACB and their role in cognitive outcomes in an older population. Cross-sectional data from 636 community-dwelling adults (73.2 ± 6.0 SD, 58.6% women) participating in the NutBrain study (2019-2023) were analyzed. Participants were asked about their medication use, and data on potential DDIs and ACB were extracted. The associations of PP (≥ 5 drugs/day), potential DDIs, and ACB with mild cognitive impairment (MCI) and specific cognitive domains were assessed using logistic regression adjusted for confounders. Sex-stratified analysis was performed. Overall, 27.2% of the participants were exposed to PP, 42.3% to potential DDIs and 19% to cumulative ACB. Women were less exposed to PP and more exposed to ACB than men. In multivariate analysis, the odds of having MCI (24%) were three times higher in those with severe ACB (≥ 3) (OR 3.34, 95%CI 1.35-8.25). ACB was positively associated with poor executive function (OR 4.45, 95%CI 1.72-11.49) and specifically with the Frontal Assessment Battery and neuropsychological tests of phonological and semantic fluency. In sex-stratified analysis, ACB was statistically significantly associated with MCI and executive function in women and with memory in men. PP, potential DDIs and anticholinergics use are very common in community-dwelling older people. ACB exposure is associated with MCI, particularly with poor executive function. Clinicians are encouraged to be vigilant when prescribing anticholinergics.Trial registration: Trial registration number NCT04461951, date of registration July 7, 2020 (retrospectively registered, ClinicalTrials.gov).

Role of fronto-limbic circuit in neuropsychiatric symptoms of dementia: clinical evidence from an exploratory study.

Background: Neuropsychiatric symptoms (NPSs) are a distressful aspect of dementia and the knowledge of structural correlates of NPSs is limited. We aimed to identify associations of fronto-limbic circuit with specific NPSs in patients with various types of cognitive impairment. Methods: Of 84 participants, 27 were diagnosed with mild cognitive impairment (MCI), 41 with Alzheimer's disease (AD) dementia and 16 with non-AD dementia. In all patients we assessed regional brain morphometry using a region of interest (ROI)-based analysis. The mean cortical thickness (CT) of 20 cortical regions and the volume (V) of 4 subcortical areas of the fronto-limbic system were extracted. NPSs were rated with the Neuropsychiatric Inventory (NPI). We used multiple linear regression models adjusted for age and disease duration to identify significant associations between scores of NPI sub-domains and MRI measures of brain morphometry. Results: All significant associations found were negative, except those between irritability and the fronto-opercular regions in MCI patients (corresponding to a 40-50% increase in CT) and between delusions and hippocampus and anterior cingulate gyrus (with a 40-60% increase). Apathy showed predominant involvement of the inferior frontal regions in AD group (a 30% decrease in CT) and of the cingulate cortex in non-AD group (a 50-60% decrease in CT). Anxiety correlated in MCI patients with the cingulate gyrus and caudate, with a CT and V decrease of about 40%, while hallucinations were associated with left enthorinal gyrus and right amygdala and temporal pole. Agitation showed associations in the AD group with the frontal regions and the temporal pole, corresponding to a 30-40% decrease in CT. Euphoria, disinhibition and eating abnormalities were associated in the MCI group with the entorhinal, para-hippocampal and fusiform gyri, the temporal pole and the amygdala (with a 40-70% decrease in CT and V). Finally, aberrant motor behavior reported a significant association with frontal and cingulate regions with a 50% decrease in CT. Conclusion: Our findings indicate that specific NPSs are associated with the structural involvement of the fronto-limbic circuit across different types of neurocognitive disorders. Factors, such as age and disease duration, can partly account for the variability of the associations observed.

[Neuropsychological evaluation and psychological intervention on patients with Parkinson's disease in physical rehabilitation]. / Valutazione neuropsicologica e intervento psicologico nei pazienti con malattia di Parkinson in riabilitazione motoria.

OBJECTIVE: Parkinson's Disease (PD) is characterized by a wide range of motor and non-motor symptoms. In the last years the evaluation of cognitive functioning, emotional aspects and health status of PD patients has became ever-growing important. METHODS: In this article a neuropsychological and psychological assessment model, by means of tests and interviews, and a clinical approach to the narrative themes are described. Areas of clinical investigation: cognitive processing, emotional acceptance and behavioural adaptation to the disease, motivation to rehabilitation treatment, expectations regarding functional recovery, adherence, social and family perceived support, mood, awareness of possible cognitive deficits. Tests assessment (based on specific cognitive deficits related to PD): MMSE, FAB, TMTA-B, Phonological verbal fluency test, Stroop test, Geriatric Depression Scale (GDS) or Beck Depression Inventory- BDI-II and Parkinson's Disease Questionnaire-8 (PDQ-8). The psychological approach, which is part of an interdisciplinary rehabilitative intervention, is based on Cognitive Behavioural Therapy and it is focused on disease management even in the absence, sometimes, of a significant general emotional status modification and it is aimed at improving patient's adaptability, self-management and empowerment. In order to describe the model, the clinical and test data of two PD patients are illustrated. CONCLUSIONS: The added value of this psychological approach lies in the clinical data integration of the test evaluation, the narrative aspects and the information mediated by the inter-professional team. This model allows a deeper and more personalized identification of the patient's subjective adjustment process according to his/her personal needs and resources.

HomeCoRe system for telerehabilitation in individuals at risk of dementia: A usability and user experience study.

Background: Telerehabilitation has enabled a broader application of cognitive rehabilitation programs. We have recently developed HomeCoRe, a system for supporting cognitive intervention remotely with the assistance of a family member. The main goal of the present study was to determine usability and user experience of HomeCoRe in individuals at risk of dementia and in their family members. The association between subjects' technological skills and main outcome measures was evaluated as well. Methods: Fourteen individuals with subjective cognitive decline (SCD) or mild neurocognitive disorder (mNCD) were recruited to participate in this pilot study. All participants received a touch-screen laptop implemented with the HomeCoRe software. The intervention consisted of 18 sessions and included a patient-tailored adaptive protocol of cognitive exercises. Usability was assessed in terms of treatment adherence and participants' performance across sessions; user experience via self-reported questionnaires and a descriptive diary. Results: Usability and user experience were overall satisfactory and suggested usability, pleasantness, and high motivation while using HomeCoRe. Technological skills correlated only with the perceived ability to start and/or perform exercises autonomously. Discussion: These results, although preliminary, suggest that the usability and user experience of HomeCoRe are satisfactory and independent of technological skills. These findings encourage wider and more systematic use of HomeCoRe to overcome the current limitations of in-person cognitive rehabilitation programs and to reach more individuals at risk of dementia.

Outcomes of a computer-based cognitive training (CoRe) in early phases of cognitive decline: a data-driven cluster analysis.

The present study aimed to identify clusters of cognitive profiles as well as to explore the effects of these clusters on demographic/individual characteristics and on improvements after a computer-based cognitive training (CCT) in early cognitive impairment. Fifty-seven subjects underwent to an adaptive CCT for 3 weeks (4 individual face-to-face sessions/week of 45 min) and were evaluated at baseline (T0), post-intervention (T1), and after 6 (T2) and 12 (T3) months. Clusters of cognitive profiles were explored with k-means analysis. The analysis revealed two clusters, which were composed by 27 and 30 patients characterized by lower (Cluster 1) and higher (Cluster 2) cognitive functioning. At T1, cognitive performance improved in both groups, but Cluster 1 gained more benefits in global cognitive functioning than Cluster 2. However, at T3, Cluster 2 remained stable in its clinical condition, whereas Cluster 1 showed a pronounced worsening. In conclusion, Cluster 1 profile was associated with a more marked but also short-lasting responsiveness to CCT, whereas patients fitting with Cluster 2 characteristics seemed to obtain more CCT benefits in terms of stability or even delay of cognitive/functional decline. These findings may have relevant implications in informing the timing and modality of delivery of CCT.

In person versus remote cognitive rehabilitation in patients with subjective cognitive decline or neurocognitive disorders: what factors drive patient's preference?

Background: To date, there is still a lack of consensus for identifying the ideal candidate for cognitive telerehabilitation (TR). The main goal of the present study is to identify the factors associated to the preference for either TR or in-person cognitive training (CT) programs in older adults at risk of dementia or with early cognitive impairment. Methods: A sample of 56 participants with subjective cognitive decline or neurocognitive disorders eligible for CT were enrolled at the Dementia Research Center and Neurorehabilitation Unit of IRCCS Mondino Foundation. All individuals underwent a baseline assessment to capture their complete profile, including cognitive reserve and lifestyle habits, sociodemographic characteristics, cognitive functioning, and mental health. Patients were then asked their preference for TR or in-person CT, before being randomized to either treatment as per protocol procedures. Statistical analyses included explorative descriptive approach, logistic regression, and non-parametric models to explore the overall contribution of each variable. Results: The two (TR and in-person) preference groups were similar for cognitive functioning and mental health status. Socio-demographic and lifestyle profiles seem to be the most important factors to influence the preference in terms of the area under the curve (AUC) of the models. The two preference groups differed in terms of socio-demographic characteristics (e.g., level of technological skills, age, and distance from the clinic). Furthermore, participants who selected the TR modality of CT had significantly higher levels of cognitive reserve and adopted more protective lifestyle habits (e.g., regular physical activity, Mediterranean diet) when compared to those who preferred in-person CT. Discussion: These findings highlight that the preference to receive CT delivered by TR or in person is a complex issue and is influenced by a variety of factors, mostly related to lifestyle habits and sociodemographic characteristics. Availability of profiles of patients that may be more attracted to one or the other modality of TR may help promote shared decision-making to enhance patient experience and outcomes.

Pre-existing mental health disorders and fear of COVID-19 pandemic: Data from a phone survey in community-dwelling older adults recruited in the NutBrain study.

Background: COVID-19 has caused a parallel epidemic of fear, anxiety, depression, stress, and frustration, particularly among the most fragile and vulnerable individuals, such as older people and those with previous mental health disorders. The present study aims to investigate the association between pre-existing mental health disorders, particularly depressive symptoms and Mild Cognitive Impairment (MCI), and the fear of COVID-19 and to explore which cognitive domains were involved in coping with fear in older people. Materials and methods: In April 2020, we conducted a phone-interview questionnaire on community-dwelling older adults living in Lombardy Region (Italy) who participated in the NutBrain study. At baseline, socio-demographic characteristics along with lifestyles, and medical history were recorded. Participants underwent a neuropsychological battery exploring the global cognitive function and specific cognitive domains, to detect cases of MCI. The Center for Epidemiologic Studies Depression scale (CES-D) was used for screening depressive symptoms. During the phone survey, respondents were assessed using a structured questionnaire querying about fear of the COVID-19 pandemic. We performed multivariate logistic regression models to study the association between MCI and depressive symptomatology and fear. We also explored which cognitive domains were associated with fear. Odds Ratios (OR) with Confidence Intervals (95%CI) were estimated adjusting for potential confounders. Results: Out of the 351 respondents (mean age 73.5 ± 6.1 years, 59.8% women, 49.1% high education), at baseline, 22.9% had MCI and 18.8% had depressive symptoms. In the multivariate analyses gender, age, and body mass index were significantly associated with the fear score. Considering different domains of fear, MCI was associated with fear of being infected themselves (OR 2.55, 95%CI 1.39-4.70) while depressive symptoms were associated with fear of contagion for family members (OR 2.38, 95%CI 1.25-4.52). Impaired executive cognitive function was positively associated with the highest tertile of the fear score (OR 3.28, 95%CI 1.37-7.74) and with fear of contagion for themselves (OR 3.39, 95%CI 1.61-7.17). Conclusion: Older adults experienced different fear reactions, particularly when suffering from neurocognitive disorders and depressive symptoms; executive dysfunction was associated with increased fear. These results highlighted the need to pay attention to the psychological effects of the outbreak of COVID-19 to target intervention, especially among vulnerable subgroups of individuals. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT04461951].

Vascular Lesions and Brain Atrophy in Alzheimer's, Vascular and Mixed Dementia: An Optimized 3T MRI Protocol Reveals Distinctive Radiological Profiles.

BACKGROUND: Vascular lesions may be a common finding also in Alzheimer's dementia, but their role on cognitive status is uncertain. OBJECTIVE: The study aims to investigate their distribution in patients with Alzheimer's, vascular or mixed dementia and detect any distinctive neuroradiological profiles. METHODS: Seventy-six subjects received a diagnosis of Alzheimer's (AD=32), vascular (VD=26) and mixed (MD=18) dementia. Three independent raters assessed the brain images acquired with an optimized 3T MRI protocol (including (3D FLAIR, T1, SWI, and 2D coronal T2 sequences) using semiquantitative scales for vascular lesions (periventricular lesions (PVL), deep white matter lesions (DWML), deep grey matter lesions (DGML), enlarged perivascular spaces (PVS), and microbleeds (MB)) and brain atrophy (medial temporal atrophy (MTA), posterior atrophy (PA), global cortical atrophy- frontal (GCA-F) and Evans' index). RESULTS: Raters reached a good-to-excellent agreement for all scales (ICC ranging from 0.78-0.96). A greater number of PVL (p<0.001), DWML (p<0.001), DGML (p=0.010), and PVS (p=0.001) was observed in VD compared to AD, while MD showed a significant greater number of PVL (p=0.001), DWML (p=0.002), DGML (p=0.018), and deep and juxtacortical MB (p=0.006 and p<0.001, respectively). Comparing VD and MD, VD showed a higher number of PVS in basal ganglia and centrum semiovale (p=0.040), while MD showed more deep and juxtacortical MB (p=0.042 and p=0.022, respectively). No significant difference was observed in scores of cortical atrophy scales and Evans' index among the three groups. CONCLUSION: The proposed MRI protocol represents a useful advancement in the diagnostic assessment of patients with cognitive impairment by more accurately detecting vascular lesions, mainly microbleeds, without a significant increase in time and resource expenditure. Our findings confirm that white and grey matter lesions predominate in vascular and mixed dementia, whereas deep and juxtacortical microbleeds predominate in mixed dementia, suggesting that cerebral amyloid angiopathy could be the main underlying pathology.