Whole-blood metabolomics of dementia patients reveal classes of disease-linked metabolites

Dementia is caused by factors that damage neurons. We quantified small molecular markers in whole blood of dementia patients, using nontargeted liquid chromatography–mass spectroscopy (LC-MS). Thirty-three metabolites, classified into five groups (A to E), differed significantly in dementia patients, compared with healthy elderly subjects. Seven A metabolites present in plasma, including quinolinic acid, kynurenine, and indoxyl-sulfate, increased. Possibly they act as neurotoxins in the central nervous system (CNS). The remaining 26 compounds (B to E) decreased, possibly causing a loss of support or protection of the brain in dementia. Six B metabolites, normally enriched in red blood cells (RBCs), all contain trimethylated ammonium moieties. These metabolites include ergothioneine and structurally related compounds that have scarcely been investigated as dementia markers, validating the examination of RBC metabolites. Ergothioneine, a potent antioxidant, is significantly decreased in various cognition-related disorders, such as mild cognitive impairment and frailty. C compounds also include some oxidoreductants and are normally abundant in RBCs (NADP+, glutathione, adenosine triphosphate, pantothenate, S-adenosyl-methionine, and gluconate). Their decreased levels in dementia patients may also contribute to depressed brain function. Twelve D metabolites contains plasma compounds, such as amino acids, glycerophosphocholine, dodecanoyl-carnitine, and 2-hydroxybutyrate, which normally protect the brain, but their diminution in dementia may reduce that protection. Seven D compounds have been identified previously as dementia markers. B to E compounds may be critical to maintain the CNS by acting directly or indirectly. How RBC metabolites act in the CNS and why they diminish significantly in dementia remain to be determined.

A cross-sectional study in healthy elderly subjects aimed at development of an algorithm to increase identification of Alzheimer pathology for the purpose of clinical trial participation

Background In the current study, we aimed to develop an algorithm based on biomarkers obtained through non- or minimally invasive procedures to identify healthy elderly subjects who have an increased risk of abnormal cerebrospinal fluid (CSF) amyloid beta42 (Aβ) levels consistent with the presence of Alzheimer’s disease (AD) pathology. The use of the algorithm may help to identify subjects with preclinical AD who are eligible for potential participation in trials with disease modifying compounds being developed for AD. Due to this pre-selection, fewer lumbar punctures will be needed, decreasing overall burden for study subjects and costs. Methods Healthy elderly subjects (n = 200; age 65–70 (N = 100) and age > 70 (N = 100)) with an MMSE > 24 were recruited. An automated central nervous system test battery was used for cognitive profiling. CSF Aβ1-42 concentrations, plasma Aβ1-40, Aβ1-42, neurofilament light, and total Tau concentrations were measured. Aβ1-42/1-40 ratio was calculated for plasma. The neuroinflammation biomarker YKL-40 and APOE ε4 status were determined in plasma. Different mathematical models were evaluated on their sensitivity, specificity, and positive predictive value. A logistic regression algorithm described the data best. Data were analyzed using a 5-fold cross validation logistic regression classifier. Results Two hundred healthy elderly subjects were enrolled in this study. Data of 154 subjects were used for the per protocol analysis. The average age of the 154 subjects was 72.1 (65–86) years. Twenty-four (27.3%) were Aβ positive for AD (age 65–83). The results of the logistic regression classifier showed that predictive features for Aβ positivity/negativity in CSF consist of sex, 7 CNS tests, and 1 plasma-based assay. The model achieved a sensitivity of 70.82% (± 4.35) and a specificity of 89.25% (± 4.35) with respect to identifying abnormal CSF in healthy elderly subjects. The receiver operating characteristic curve showed an AUC of 65% (± 0.10). Conclusion This algorithm would allow for a 70% reduction of lumbar punctures needed to identify subjects with abnormal CSF Aβ levels consistent with AD. The use of this algorithm can be expected to lower overall subject burden and costs of identifying subjects with preclinical AD and therefore of total study costs. Trial registration ISRCTN.org identifier: ISRCTN79036545 (retrospectively registered).

Effect of haemoglobin deficiency on cognitive functions in elderly of Bangalore city

Adequate nutrition is fundamental to healthy ageing. Among older adults with anaemia, approximately one-third have evidence of iron, folate, and/or vitamin B deficiency. Lower haemoglobin levels are common in older adults and frequently are measured in clinical practice.1. To assess haemoglobin levels in elderly. 2. To assess cognitive functions in different levels of haemoglobin. This study involved 80 healthy elderly subjects with consideration of inclusion and exclusion criteria. Written informed consent was taken. For each subject, blood sample of 4ml was collected for Haemoglobin assessment. Anthropometric measurements were taken. 24-hour dietary recall, General history questionnaire and Spreen & Stauss Neuropsychology battery of tests were administered.Results were compiled and statistically analyzed. The results show that Elderly with haemoglobin deficiency had statistically significant low scores in all parameters (P < 0.05), especially with executive function & processing speed.It can be concluded that haemoglobin levels were associated with worse global cognitive function and greater decline in psychomotor speed and executive function.

Factors Associated With the Dilation of Perivascular Space in Healthy Elderly Subjects

Background: The dilation of perivascular space (PVS) has been widely used to reflect brain degeneration in clinical brain imaging studies. However, PVS characteristics exhibit large differences in healthy subjects. Such variations need to be better addressed before PVS can be used to reflect pathological changes. In the present study, we aim to investigate the potential influence of several related factors on PVS dilation in healthy elderly subjects.Methods: One-hundred and three subjects (mean age = 59.5) were retrospectively included from a prospectively collected community cohort. Multi-modal high-resolution magnetic resonance imaging and cognitive assessments were performed on each subject. Machine-learning based segmentation methods were employed to quantify PVS volume and white matter hyperintensity (WMH) volume. Multiple regression analysis was performed to reveal the influence of demographic factors, vascular risk factors, intracranial volume (ICV), major brain artery diameters, and brain atrophy on PVS dilation.Results: Multiple regression analysis showed that age was positively associated with the basal ganglia (BG) (standardized beta = 0.227, p = 0.027) and deep white matter (standardized beta = 0.220, p = 0.029) PVS volume. Hypertension was positively associated with deep white matter PVS volume (standardized beta = 0.234, p = 0.017). Furthermore, we found that ICV was strongly associated with the deep white matter PVS volume (standardized beta = 0.354, p < 0.001) while the intracranial artery diameter was negatively associated with the deep white matter PVS volume (standardized beta = −0.213, p = 0.032).Conclusions: Intracranial volume has significant influence on deep white matter PVS volume. Future studies on PVS dilation should include ICV as an important covariate.

A RANDOMISED DOUBLE-BLIND CLINICAL STUDY TO EVALUATE AND COMPARE THE EFFECTS OF VRIDDADARU RASAYANA WITH BHARGAVAPROKTA RASAYANA ON AGEING IN APPARENTLY HEALTHY ELDERLY SUBJECTS

According to estimation, India currently has 6.7% over 65 years of age, which is expected to increase to 20% by the year 2050. As growing old is a part of the life cycle, the effect of time is bound to happen and is unavoidable. The Kalajajara is a Swabhavika vyadhi, wherein, it is clearly mentioned that Swabhava balapravritta vyadhis being Yapya, can be managed through Bhojana, Paana, and Rasayana. Vriddadaru Rasayana is one such Rasayana mentioned in Gadanigraha especially for the elderly to promote healthy ageing and helping to prevent old age problems. Aims and objectives: To assess the effect of Vriddadaru Rasayana in improving the general body health and quality of life in the apparently healthy elderly subjects. Methodology– A Randomized double blind clinical study where 20 healthy elderly subjects were administered with Vriddadaru Rasayana for a period of 12 weeks. Observations and Results- Vriddadaru rasayana showed improvement in Ayurvedic parameters like Twakparushata, Slataasti, Slata sandhi, Utasahahani and Parakramahani but when compared with regard to objective parameters Vriddadaru rasayana showed significant values in DHEAS levels and 6MWT. Conclusion: Vriddadaru does Vatashamana, balancing the Doshas, increasing the Utsaha and Parakrama and helps in improving the Agni thus helping in Dhatuposhana in the elderly.