Ana Verdelho

Neurodegenerative Diseases (NDs) present a significant health challenge. Therefore, finding reliable blood biomarkers for these diseases has been of pivotal importance in translational/clinical research. However, conventional omics struggle with the complexity of blood samples, which makes it difficult to achieve the desired goal. To address this, the potential of High Molecular Weight (HMW) serum fractionation under non-denaturing conditions as a complementary approach to the direct analysis of whole serum proteomics was explored in this work. To achieve this, a total of 58 serum samples of Alzheimer's disease (AD), Parkinson's disease (PD) patients and control individuals underwent two strategies: i) direct analysis of whole serum and ii) non-denaturing fractionation using 300 kDa cut-off filters (HMW serum). As expected, each approach was able to capture different sets of differentially regulated proteins since most of the altered proteins were not shared between them. More importantly, it was possible to create a discriminant model using the altered proteins from both datasets capable of distinguishing the three groups (AUC = 0.999 and, median sensitivity and specificity of 97.4% and 91.7%, respectively). Altogether, this work demonstrated that HMW fractionation can be a valuable complementary method to direct serum analysis and could enhance biomarker discovery. The 10 proteins included in the model (5 from each strategy), comprise clear evidence for the contribution of apolipoproteins for the diagnosis of NDs, revealing potential changes within lipid metabolism and the organization of macromolecules and their complexes, thereby uncovering effects that remain hidden from a conventional serum proteome analysis.

Purpose: To investigate the relationship between age‐related white matter hyperintensities (WMHs) and lower urinary tract symptoms (LUTS) in functionally independent older adults by integrating neurological and urological evaluations. Materials and Methods: This observational prospective cohort study (One Step Towards Overactive Bladder Phenotyping [OSTOAP Study]) included 59 community‐dwelling individuals aged ≥ 55 years with MRI evidence of cerebral small vessel disease. Participants underwent standardized neurological evaluation, Montreal Cognitive Assessment (MoCA), and WMH classification using the Fazekas scale. WMHs were categorized into mild (Fazekas 1) and moderate‐to‐severe (Fazekas 2–3). Urological assessment included validated questionnaires, a 3‐day bladder diary, uroflowmetry, and post‐void residual (PVR) measurement. Multivariable regression models identified predictors of LUT dysfunction. Results: Participants with moderate‐to‐severe WMHs had more urgency episodes (median [IQR]: 3 [1–4] vs. 1 [0–2], p = 0.001) and higher PVR volumes (median [IQR]: 50 [0–90] vs. 0 [0–20], p = 0.012). WMH burden independently predicted urgency (OR = 3.51; p = 0.014) and PVR ≥ 50 mL (OR = 3.25; p = 0.014), after adjusting for age, MoCA, and comorbidities. Questionnaire scores and prostate volume did not differ significantly. Increasing age was associated with reduced maximum voided volume ( β = −0.516, p < 0.001). Conclusions: Moderate‐to‐severe WMHs are independently associated with urgency and impaired bladder emptying. These findings suggest that cerebral small vessel disease may contribute to LUT dysfunction in older adults and support the inclusion of neurological screening in their evaluation, reinforcing the value of integrative phenotyping in future studies.

Introduction: The intermediate stages of dementia are relatively under-researched, including in Portugal. The Actifcare (ACcess to TImely Formal Care) EU-JPND project studied people with mild-moderate dementia, namely their needs, access to and use of community services (e.g., day centers, home support). In our baseline assessment of the Portuguese Actifcare cohort, the unmet needs of some participants would call for formal support, which was not always accessible or used. We now report the main results of the 12-month follow-up, analyzing changes in needs, service (non)use, quality of life and related variables.Methods: This was a longitudinal, observational study using a convenience sample of 54 dyads of people with dementia and their family carers. Our main outcomes were the Camberwell Assessment of Need for the Elderly (CANE) and the Resources Utilization in Dementia. Clinical-functional, quality of life, psychological distress and caregiving-related assessments were also used.Results: At follow-up, the cognitive and functional status of people with dementia declined (p < 0.001), and their neuropsychiatric symptoms increased (p = 0.033). Considering CANE interviewers’ ratings, the total needs of people with dementia increased at follow-up (p < 0.001) but not the unmet needs. Quality of life was overall stable. The use of formal care did not increase significantly, but informal care did in some domains. Carers’ depressive symptoms increased (p = 0.030) and perseverance time decreased (p = 0.045). However, carers’ psychological distress unmet needs were lower (p = 0.007), and their stress and quality of life remained stable.Conclusion: People with dementia displayed complex biopsychosocial unmet needs. Their cognitive-functional decline over one year was not accompanied by a corresponding increase in any pattern of unmet need, nor of service use. Reliance on informal care (namely supervision) may have contributed to this. Caregiving-related outcomes evolved according to different trends, although stability was almost the rule. Primary carers were even more present at follow-up, without an apparently heavier toll on their own needs, burden, and quality of life. Overall, this longitudinal study comprehensively assessed Portuguese community-dwelling people with dementia. Despite the lack of generalizability, participants’ needs remained overall stable and partly unmet over one year. Longer follow-up periods are needed to understand such complex processes. Introdução: As fases intermédias da demência têm sido menos investigadas. O projecto EU-JPND Actifcare (ACcess to TImely Formal Care) estudou as necessidades de pessoas com demência ligeira-moderada e o acesso/utilização de serviços na comunidade (v.g., centros de dia, apoio domiciliário). Na avaliação inicial da subamostra portuguesa, as necessidades não cobertas de alguns participantes exigiriam apoio formal, nem sempre disponível ou procurado. Apresentamos agora resultados do estudo longitudinal (12 meses), analisando necessidades, utilização dos serviços, qualidade de vida e variáveis relacionadas.Métodos: Estudo longitudinal de uma amostra de conveniência (54 díades doente/familiar-cuidador). Além dos principais instrumentos (Camberwell Assessment of Need for the Elderly - CANE, Resources Utilization in Dementia), foram realizadas avaliações complementares: clínico-funcionais, qualidade de vida, sofrimento psicológico, experiência de cuidar.Resultados: No follow-up, o estado cognitivo e funcional das pessoas com demência piorou (p < 0,001) e os sintomas neuropsiquiátricos aumentaram (p = 0,033). O total de necessidades aumentou (p < 0,001), mas o total de necessidades não cobertas e a qualidade de vida permaneceram estáveis. A utilização de cuidados formais não aumentou significativamente, mas os cuidados informais sim (nalguns domínios). Os sintomas depressivos dos familiares-cuidadores aumentaram (p = 0,030), diminuindo o tempo de perseverança (p = 0,045). Porém, as suas necessidades não cobertas de sofrimento psicológico foram menores (p = 0,007), enquanto o stress e a qualidade de vida permaneceram estáveis.Conclusão: Estas pessoas com demência apresentavam necessidades biopsicossociais complexas e não cobertas. O declínio cognitivo-funcional ao longo de um ano não foi, aparentemente, acompanhado por um aumento de necessidades não cobertas, nem da utilização de serviços. A maior utilização dos cuidados informais (supervisão) pode ter contribuído para tal. A análise das dimensões da experiência de cuidar sugere tendências não inteiramente uniformes, embora a estabilidade fosse quase a regra. Os familiares-cuidadores ‘primários’ estavam ainda mais presentes no follow-up, sem que isso pareça ter alterado as suas próprias necessidades, sobrecarga e qualidade de vida. Em suma, apresentamos uma análise longitudinal abrangente de uma amostra comunitária de famílias de pessoas com demência ligeira-moderada. Não sendo os resultados generalizáveis, ao fim de um ano as necessidades dos participantes mantiveram-se globalmente estáveis e parcialmente não cobertas. Para compreender processos tão complexos, necessitamos de estudos com tempos de seguimento maiores.

Purpose: Practical suggestions on clinical decisions about vascular disease management in patients with cognitive impairment are proposed. Methods: The document was produced by the Dementia Committee of the European Stroke Organisation (ESO) based on the evidence from the literature where available and on the clinical experience of the Committee members. This paper was endorsed by the ESO. Findings: Vascular risk factors and cerebrovascular disease are frequent in patients with cognitive impairment. While acute stroke treatment has evolved substantially in last decades, evidence of management of cerebrovascular pathology beyond stroke in patients with cognitive impairment and dementia is quite limited. Additionally, trials to test some daily-life clinical decisions are likely to be complex, difficult to undertake and take many years to provide sufficient evidence to produce recommendations. This document was conceived to provide some suggestions until data from field trials are available. It was conceived for the use of clinicians from memory clinics or involved specifically in cognitive disorders, addressing practical aspects on diagnostic tools, vascular risk management and suggestions on some therapeutic options. Discussion and conclusions: The authors did not aim to do an exhaustive or systematic review or to cover all current evidence. The document approach in a very practical way frequent issues concerning cerebrovascular disease in patients with known cognitive impairment.

Many daily-life clinical decisions in patients with cerebrovascular disease and cognitive impairment are complex. Evidence-based information sustaining these decisions is frequently lacking. The aim of this paper is to propose a practical clinical approach to cognitive impairments in patients with known cerebrovascular disease. The document was produced by the Dementia Committee of the European Stroke Organisation (ESO), based on evidence from the literature where available and on the clinical experience of the Committee members. This paper was endorsed by the ESO. Many patients with stroke or other cerebrovascular disease have cognitive impairment, but this is often not recognized. With improvement in acute stroke care, and with the ageing of populations, it is expected that more stroke survivors and more patients with cerebrovascular disease will need adequate management of cognitive impairment of vascular etiology. This document was conceived for the use of strokologists and for those clinicians involved in cerebrovascular disease, with specific and practical hints concerning diagnostic tools, cognitive impairment management and decision on some therapeutic options. Discussion and conclusions: It is essential to consider a possible cognitive deterioration in every patient who experiences a stroke. Neuropsychological evaluation should be adapted to the clinical status. Brain imaging is the most informative biomarker concerning prognosis. Treatment should always include adequate secondary prevention.

Mild cognitive impairment (MCI) is characterized by cognitive, psychological, and functional impairments. Digital interventions typically focus on cognitive deficits, neglecting the difficulties that patients experience in instrumental activities of daily living (IADL). The global conjecture created by COVID-19 has highlighted the seminal importance of digital interventions for the provision of healthcare services. Here, we investigated the feasibility and rehabilitation potential of a new design approach for creating highly realistic interactive virtual environments for MCI patients’ neurorehabilitation. Through a participatory design protocol, a neurorehabilitation digital platform was developed using images captured from a Portuguese supermarket (NeuroVRehab.PT). NeuroVRehab.PT’s main features (e.g., medium-sized supermarket, the use of shopping lists) were established according to a shopping behavior questionnaire filled in by 110 older adults. Seven health professionals used the platform and assessed its rehabilitation potential, clinical applicability, and user experience. Interviews were conducted using the think-aloud method and semi-structured scripts, and four main themes were derived from an inductive semantic thematic analysis. Our findings support NeuroVRehab.PT as an ecologically valid instrument with clinical applicability in MCI neurorehabilitation. Our design approach, together with a comprehensive analysis of the patients’ past experiences with IADL, is a promising technique to develop effective digital interventions to promote real-world functioning.