Stratification of the Gut Microbiota Composition Landscape across the Alzheimer's Disease Continuum in a Turkish Cohort.

Alzheimer's disease (AD) is a heterogeneous disorder that spans a continuum with multiple phases, including preclinical, mild cognitive impairment, and dementia. Unlike for most other chronic diseases, human studies reporting on AD gut microbiota in the literature are very limited. With the scarcity of approved drugs for AD therapies, the rational and precise modulation of gut microbiota composition using diet and other tools is a promising approach to the management of AD. Such an approach could be personalized if an AD continuum can first be deconstructed into multiple strata based on specific microbiota features by using single or multiomics techniques. However, stratification of AD gut microbiota has not been systematically investigated before, leaving an important research gap for gut microbiota-based therapeutic approaches. Here, we analyze 16S rRNA amplicon sequencing of stool samples from 27 patients with mild cognitive impairment, 47 patients with AD, and 51 nondemented control subjects by using tools compatible with the compositional nature of microbiota. To stratify the AD gut microbiota community, we applied four machine learning techniques, including partitioning around the medoid clustering and fitting a probabilistic Dirichlet mixture model, the latent Dirichlet allocation model, and we performed topological data analysis for population-scale microbiome stratification based on the Mapper algorithm. These four distinct techniques all converge on Prevotella and Bacteroides stratification of the gut microbiota across the AD continuum, while some methods provided fine-scale resolution in stratifying the community landscape. Finally, we demonstrate that the signature taxa and neuropsychometric parameters together robustly classify the groups. Our results provide a framework for precision nutrition approaches aiming to modulate the AD gut microbiota. IMPORTANCE The prevalence of AD worldwide is estimated to reach 131 million by 2050. Most disease-modifying treatments and drug trials have failed, due partly to the heterogeneous and complex nature of the disease. Recent studies demonstrated that gut dybiosis can influence normal brain function through the so-called "gut-brain axis." Modulation of the gut microbiota, therefore, has drawn strong interest in the clinic in the management of the disease. However, there is unmet need for microbiota-informed stratification of AD clinical cohorts for intervention studies aiming to modulate the gut microbiota. Our study fills in this gap and draws attention to the need for microbiota stratification as the first step for microbiota-based therapy. We demonstrate that while Prevotella and Bacteroides clusters are the consensus partitions, the newly developed probabilistic methods can provide fine-scale resolution in partitioning the AD gut microbiome landscape.

Frailty in Patients with Parkinson's Disease: Associations with Disability and Timed Up and Go.

INTRODUCTION: Aim of this study was identify the prevalence of frailty in patients with idiopathic Parkinson's disease (PD), to describe the relationship between severity of the disease and frailty, and to evaluate if timed up and go (TUG) is an eligible test for determination of frailty in idiopathic PD patients. METHODS: We conducted a cross-sectional study which included 66 patients, aged 60 and over in a tertiary hospital. Frailty was assessed by the Fried Frailty Index (FFI). Severity of the idiopathic PD was detected by the Hoehn and Yahr (H&Y) scale. Mobility was measured by the TUG test. Demographic characteristics and comprehensive geriatric assessments were evaluated. Descriptive statistics and logistic regression were used in analyses. Receiver operating characteristic (ROC) curves were used to identify the discriminative effect of TUG test on frailty. RESULTS: The numbers of frail, prefrail, and robust subjects were 34 (51.5%), 24 (36.4%), and 8 (12.1%), respectively. Dependency in instrumental activities of daily living (IADL) was significantly associated with frailty (Odds ratio (OR): 36.00, Confidence interval (CI): 8.43-153.80). Multivariate logistic regression analysis results yielded, depression (OR: 10.37, CI: 2.82-38.12) and higher levodopa doses (OR: 6.28, CI: 1.77-22.24) were independently associated with frailty. TUG test performance was strongly associated with frailty with high sensitivity (0.806) and specificity (0.826) (Area under the curve (AUC): 0.831). CONCLUSIONS: Frailty is highly prevalent in idiopathic PD and is strongly associated with disabilities as well as specific risk factors of the disease. The TUG may be a reliable test for prediction of frailty in patients with idiopathic PD.

Adaptation and Norm Determination Study of the Boston Naming Test for Healthy Turkish Elderly.

INTRODUCTION: The main purpose of this research is develop the Turkish version of the BNT long form (consist of 60 items) [BNT-60 (TR)] and to determine the normative data for Turkish healthy geriatric population. BNT is a neuropsychological test which was widely used to measure naming disorders associated with a variety of neuropathological events. This research consists of two stages. In the stage of pilot study, adaptation of test was completed and BNT-60 (TR) version was developed; and in the stage of normative study, normative data was collected and norm determination was completed. METHODS: Ninety healthy and volunteer elderly were participated in pilot study and 317 were in normative study. Three screening tests called Montreal Cognitive Assessment (MOCA), Functional Activities Questionnaire (FAQ) and Geriatric Depression Scale (GDS) were administered for participant selection. BNT-60 (TR) was applied to participants who meet the inclusion criteria. RESULTS: According to 5 (age) x 2 (gender) x 3 (education) factorial ANOVA results, main effects of age and education level on BNT-60 (TR) total score were found statistically significant. Then according to MANOVA results, main effects of age and education level on BNT-60 (TR) sub-scores were found statistically significant. On the other hand, main effect of gender was not significant on BNT-60 (TR) scores. The age and BNT-60 (TR) total score were negatively correlated. This results consistent with other normative studies of BNT in the literature. CONCLUSION: Finally, BNT-60 (TR) is adopted for Turkish culture, determined normative data and a test which is evaluating naming ability of the older adults was put into use.