Potential Protein Blood-based Biomarkers in Different Types of Dementia: A Therapeutic Overview.

Biomarkers capable of identifying and distinguishing types of dementia, such as Alzheimer's disease (AD), Parkinson's disease dementia (PDD), Lewy body dementia (LBD), and frontotemporal dementia (FTD), have become increasingly relentless. Studies on possible biomarker proteins in the blood that can help formulate new diagnostic proposals and therapeutic visions of different types of dementia are needed. However, due to several limitations of these biomarkers, especially in discerning dementia, their clinical applications are still undetermined. Thus, updating biomarker blood proteins that can help in the diagnosis and discrimination of these main dementia conditions is essential to enable new pharmacological and clinical management strategies with specificities for each type of dementia. This paper aimed to review the literature concerning protein bloodbased AD and non-AD biomarkers as new pharmacological targets and/or therapeutic strategies. Recent findings related to protein-based AD, PDD, LBD, and FTD biomarkers are focused on in this review. Protein biomarkers are classified according to the pathophysiology of the dementia types. The diagnosis and distinction of dementia through protein biomarkers is still a challenge. The lack of exclusive biomarkers for each type of dementia highlights the need for further studies in this field. Only after this, blood biomarkers may have a valid use in clinical practice as they are promising to help in the diagnosis and in the differentiation of diseases.

Associations between inflammatory markers and muscle strength in older adults according to the presence or absence of obesity.

BACKGROUND: We investigated the association between inflammatory markers and muscle strength in older adults according to the presence or absence of obesity. Dynapenia is the age-related decline in muscle strength and results in negative outcomes to older adults. Accordingly, obesity is more prevalent throughout aging and is associated with comorbidities, such as type 2 diabetes, dyslipidemia and cardiovascular diseases. Both dynapenia and obesity are strongly linked to chronic inflammation, sharing common signaling pathways. METHODS: We recruited 247 older adults aged 60 or older and collected sociodemographic, anthropometric and metabolic data. Dynapenia was diagnosed according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Circulating inflammatory cytokines were measured in plasma using a multiplex panel kit. Anthropometric, sociodemographic, lipid profile, and fasting blood glucose were also assessed. RESULTS: Dynapenic participants were predominantly males (74.4%), had insufficiently active lifestyle and higher IL-10 plasma levels (0.95 pg/mL; 0.40-2.12). The prevalence of obesity was higher among non-dynapenic participants (45.3%; 95% CI, 37.7-53). In dynapenic older adults, obesity was predominant in males (53.6%) and subjects with normal muscle strength had higher serum levels of TNF-ß (0.63 pg/mL; 0.30-1.30) and lower hand-grip strength (24 kg; 20.00-28.00). Using a multivariate quantile regression analysis, we found a strong and negative association between IL-10 and muscle strength. CONCLUSIONS: This study can help to understand the association of inflammation, obesity and muscle strength to promote interventions in order to avoid or delay the negative outcomes associated with dynapenia and sarcopenia in older adults.

Blood-based Biomarkers of Alzheimer's Disease: The Long and Winding Road.

BACKGROUND: Blood-based biomarkers can be very useful in formulating new diagnostic and treatment proposals in the field of dementia, especially in Alzheimer's disease (AD). However, due to the influence of several factors on the reproducibility and reliability of these markers, their clinical use is still very uncertain. Thus, up-to-date knowledge about the main blood biomarkers that are currently being studied is extremely important in order to discover clinically useful and applicable tools, which could also be used as novel pharmacological strategies for the AD treatment. METHODS: A narrative review was performed based on the current candidates of blood-based biomarkers for AD to show the main results from different studies, focusing on their clinical applicability and association with AD pathogenesis. OBJECTIVE: The aim of this paper was to carry out a literature review on the major blood-based biomarkers for AD, connecting them with the pathophysiology of the disease. RESULTS: Recent advances in the search of blood-based AD biomarkers were summarized in this review. The biomarkers were classified according to the topics related to the main hallmarks of the disease such as inflammation, amyloid, and tau deposition, synaptic degeneration and oxidative stress. Moreover, molecules involved in the regulation of proteins related to these hallmarks were described, such as non-coding RNAs, neurotrophins, growth factors and metabolites. Cells or cellular components with the potential to be considered as blood-based AD biomarkers were described in a separate topic. CONCLUSION: A series of limitations undermine new discoveries on blood-based AD biomarkers. The lack of reproducibility of findings due to the small size and heterogeneity of the study population, different analytical methods and other assay conditions make longitudinal studies necessary in this field to validate these structures, especially when considering a clinical evaluation that includes a broad panel of these potential and promising blood-based biomarkers.

Higher levels of tumor necrosis factor ß are associated with frailty in socially vulnerable community-dwelling older adults.

BACKGROUND: The complex physiology underpinning the frailty syndrome is responsible for the absence of robust biomarkers that can be used for screening, diagnostic and/or prognostic purposes and has made clinical implementation difficult. Considering socially vulnerable populations, who have poor health status and increased morbidity and mortality, this scenario is even more complex. However, to the best of our knowledge, there are no studies available to investigate frailty biomarkers in socially vulnerable populations. Thus, the aim of this cross-sectional study was to identify potential blood-based biomarkers of frailty in a socially vulnerable population. METHODS: A sample consisting of 347 community-dwelling older people living in a context of high social vulnerability was divided into non-frail (robust), pre-frail and frail groups, according to modified Fried frailty phenotype criteria. Blood samples were collected and analyzed for basic metabolic parameters and for inflammatory cytokines. RESULTS: Levels of Interleukin-1α (IL-1α) and Tumor Necrosis Factor α (TNF-α) were significantly higher in pre-frail subjects, compared to non-frail ones. Tumor Necrosis Factor ß (TNF-ß) levels presented higher values in the frail compared to non-frail individuals. Interleukin-6 (IL-6) levels in pre-frail and frail subjects were significantly higher compared to the levels of non-frail subjects. Using an ordinal regression analysis, we observed that socially vulnerable older people at higher risk of developing frailty were subjects above 80 years old (OR: 2.5; 95% CI: 1.1-5.6) and who presented higher levels of TNF-ß (≥0.81 pg/mL, OR: 2.53; 95% CI: 1.3-4.9). CONCLUSION: As vulnerable populations continue to age, it is imperative to have a greater understanding of the frailty condition, identifying novel potential blood-based biomarkers. The results presented here could help to implement preventive healthcare strategies by evaluating frailty and at the same time measuring a set of inflammatory biomarkers, paying special attention to TNF-ß plasmatic levels.

A controlled clinical trial on the effects of exercise on neuropsychiatric disorders and instrumental activities in women with Alzheimer's disease / Efeitos do exercício físico sobre distúrbios neuropsiquiátricos e atividades instrumentais da vida diária em mulheres com doença de Alzheimer : um ensaio clínico controlado

OBJECTIVE: To analyze the influence of a six-month exercise program on neuropsychiatric disorders and on the performance of instrumental activities in elderly patients with Alzheimer's disease (AD). METHODS: The study included 20 patients with AD in the mild to moderate stages of the Clinical Dementia Rating (CDR) divided into two groups: the experimental group, composed of 10 women who participated in the six-month exercise program, and the control group, composed of the 10 remaining AD patients who did not take part in an exercise program during the same period. All participants were evaluated using the Mini-Mental State Exam for global cognitive function, the Neuropsychiatric Inventory Questionnaire for neuropsychiatric disorders, and the Pfeffer Functional Activities Questionnaire for the degree of functional impairment. RESULTS: The control group showed functional and neuropsychiatric deterioration in the comparisons between pre- and post-intervention times and between groups. CONCLUSION: The experimental group showed a propensity for less deterioration in neuropsychiatric disorders and performance of instrumental activities compared to the sedentary group.

OBJETIVO: Analisar os efeitos de seis meses de intervenção de um programa de atividade física sobre os distúrbios neuropsiquiátricos e o desempenho nas atividades instrumentais da vida diária de idosos com Doença de Alzheimer (DA). MÉTODOS: Foram recrutados 20 pacientes nos estágios entre leve e moderado da DA. Segundo o escore clínico de demência (CDR), foram distribuídos em dois grupos: o grupo treinamento (GT), composto por dez mulheres que participaram de um program de exercícios físicos por um período de seis meses, e o grupo controle (GC), composto por dez outras participantes que não realizaram nenhum tipo de intervenção motora estruturada durante o mesmo período. Todas as participantes foram avaliadas por meio do Miniexame do Estado Mental, para obtenção da caracterização cognitiva; Inventário Neuropsiquiátrico, para identificação dos distúrbios neuropsiquiátricos mais prevalentes e Questionário de Atividades Instrumentais de Pfeffer, para verificação do grau de comprometimento funcional. RESULTADOS: Os participantes do GC mostraram uma deterioração tanto no desempenho das atividades instrumentais quanto na intensificação dos distúrbios neuropsiquiátricos, quando comparados os momentos pré e pós-intervenção. CONCLUSÃO: O GT demonstrou uma atenuação da intensificação dos distúrbios neuropsiquiátricos e do desempenho funcional em relação ao grupo sedentário.

A controlled clinical trial on the effects of exercise on neuropsychiatric disorders and instrumental activities in women with Alzheimer's disease.

OBJECTIVE: To analyze the influence of a six-month exercise program on neuropsychiatric disorders and on the performance of instrumental activities in elderly patients with Alzheimer's disease (AD). METHODS: The study included 20 patients with AD in the mild to moderate stages of the Clinical Dementia Rating (CDR) divided into two groups: the experimental group, composed of 10 women who participated in the six-month exercise program, and the control group, composed of the 10 remaining AD patients who did not take part in an exercise program during the same period. All participants were evaluated using the Mini-Mental State Exam for global cognitive function, the Neuropsychiatric Inventory Questionnaire for neuropsychiatric disorders, and the Pfeffer Functional Activities Questionnaire for the degree of functional impairment. RESULTS: The control group showed functional and neuropsychiatric deterioration in the comparisons between pre- and post-intervention times and between groups. CONCLUSION: The experimental group showed a propensity for less deterioration in neuropsychiatric disorders and performance of instrumental activities compared to the sedentary group.