There is a lack of normative studies of the Mini-Mental State Examination (MMSE) for comparison with early Alzheimer's disease (AD) according to new diagnostic criteria.
We administered the MMSE to ...normal elderly Czechs and to patients with mild cognitive impairment (MCI) and mild dementia due to AD according to NIA-AA criteria.
We established percentile- and standard deviation-based norms for the MMSE from 650 normal seniors (age 69 ± 8 years, education 14 ± 3 years, MMSE score 28 ± 2 points) stratified by education and age. Dementia patients scored significantly lower than the MCI patients and both groups (110 early AD patients) had significantly lower MMSE scores than the normal seniors (22 ± 5 or 25 ± 3 vs. 28 ± 2 points) (p < 0.01). The optimal cutoff was ≤27 points with sensitivity of 86% and specificity of 79% for early detection of AD patients.
We provided MMSE norms, several cutoffs, and higher cutoff scores for early AD using recent guidelines.
Alzheimer's disease (AD) is the most common type of dementia. In connection with the global trend of prolonging human life and the increasing number of elderly in the population, the AD becomes one ...of the most serious health and socioeconomic problems of the present. Tau protein promotes assembly and stabilizes microtubules, which contributes to the proper function of neuron. Alterations in the amount or the structure of tau protein can affect its role as a stabilizer of microtubules as well as some of the processes in which it is implicated. The molecular mechanisms governing tau aggregation are mainly represented by several posttranslational modifications that alter its structure and conformational state. Hence, abnormal phosphorylation and truncation of tau protein have gained attention as key mechanisms that become tau protein in a pathological entity. Evidences about the clinicopathological significance of phosphorylated and truncated tau have been documented during the progression of AD as well as their capacity to exert cytotoxicity when expressed in cell and animal models. This paper describes the normal structure and function of tau protein and its major alterations during its pathological aggregation in AD.
This study presents results of our randomized clinical trial studying the effect of human probiotics on memory and psychological and physical measures following our study protocol registered at ...clinicaltrials.gov NCT05051501 and described in detail in our previous paper.
Community dwelling participants aged between 55 and 80 years were randomly assigned to receive a single dose of 10
colony-forming units of human
GH,
GH NEXARS, Lactobacilus plantarum GH, and
GH or placebo. A cross-over design allowed each group to receive probiotics and placebo for 3 months each in reverse order. A small subset of participants was examined online due to the COVID-19 pandemic. After 6 months a small number of volunteers were additionally assessed after 2 months without any intervention. Primary outcome measures included changes in cognitive functions assessed using brief tests and a neuropsychological battery and changes in mood assessed using validated questionnaires. Secondary outcome measures included changes in self-report and subjective measures using depression and anxiety questionnaires, seven visual analog scales of subjective feelings (memory, digestion, etc.), and physical performance.
At baseline, the probiotic-placebo group A (
= 40, age 69 ± 7 years, education 16 ± 3 years, 63% females, body mass index 28.5 ± 6, subjective memory complaint in 43%) did not differ from the placebo-probiotic group B (
= 32) in any of the sociodemographic characteristics and evaluated measures including cognitive status. At follow-up visits after 3, 6, and 8 months, no cross-sectional differences in any of the measures were found between the groups except worse sentence recall of the ALBA test after 3 months of probiotic use. Score changes were not observed for all cognitive tests but one in any group between visits 1 and 3 and between visits 3 and 6. The only change was observed for the TMT B test after the first three months but no change was observed after the second three months.
The treatment with human probiotics and prebiotics did not improve cognitive, affective, or physical measures in community-dwelling individuals with normal or mildly impaired cognitive functions.
clinicaltrials.gov, identifier NCT05051501.
Background
Gut microbiota may influence brain functions. Therefore, we prepared a study protocol for a double-blind, crossover, randomized clinical trial to determine the complex effects of human ...probiotics on memory, psychological, and biological measures in the elderly.
Methods
We selected eligible participants using an effective electronic questionnaire containing the inclusion and exclusion criteria and a brief electronic cognitive test. One-third of the respondents with the worst cognitive scores on the electronic test are randomized to group A, starting with a 3-month probiotic intervention, and to group B, starting with a placebo. In a crossover design, both groups change their intervention/placebo status after 3 months for the next 3 months. Participants refusing longer personal assessments due to the COVID-19 pandemic were randomly allocated to one of two subgroups assessed online. Participants in both groups are matched in age, education, gender, and cognitive scores on electronic testing at baseline. At three time points, participants are assessed using a neuropsychological battery, self-report measures of mood, a physical fitness test, blood, urine, and stool samples, and actigraphy. A subset of participants also provided their biological samples and underwent the neuropsychological battery in an extended testing phase 3 months after study termination to find out the long-term effect of the intervention.
Discussion
This is the first trial to address the comprehensive effects of human probiotics on memory and many other measures in the elderly. We assume that the probiotic group will have better outcomes than the placebo group after the first and second trimesters. We expect that the probiotic effect will persist for the next 3 months. These study’s findings will contribute to an interesting area of how to improve memory, psychological and biological and other factors naturally and will examine the importance of probiotics for overall health in the elderly.
Clinical trial registration
clinicaltrials.gov
, identifier NCT05051501.
Alzheimer's disease (AD) is a neurodegenerative disease often accompanied with disruption of sleep-wake cycle. The sleep-wake cycle is controlled by mechanisms involving internal timekeeping ...(circadian) regulation. The aim of our present pilot study was to assess the circadian system in patients with mild form of AD in their home environment. In the study, 13 elderly AD patients and 13 age-matched healthy control subjects (the patient's spouses) were enrolled. Sleep was recorded for 21 days by sleep diaries in all participants and checked by actigraphy in 4 of the AD patient/control couples. The samples of saliva and buccal mucosa were collected every 4 hours during the same 24 h-interval to detect melatonin and clock gene (PER1 and BMAL1) mRNA levels, respectively. The AD patients exhibited significantly longer inactivity interval during the 24 h and significantly higher number of daytime naps than controls. Daily profiles of melatonin levels exhibited circadian rhythms in both groups. Compared with controls, decline in amplitude of the melatonin rhythm in AD patients was not significant, however, in AD patients more melatonin profiles were dampened or had atypical waveforms. The clock genes PER1 and BMAL1 were expressed rhythmically with high amplitudes in both groups and no significant differences in phases between both groups were detected. Our results suggest moderate differences in functional state of the circadian system in patients with mild form of AD compared with healthy controls which are present in conditions of their home dwelling.
The aim of this study was to evaluate the diagnostic potential of cerebrospinal fluid (CSF) and serum levels of neurocytoskeletal proteins and their ratios for the diagnosis of dementias and to ...assess the differences in neurocytoskeletal proteins between neurodegeneration and neuroinflammation.
CSF and serum levels of neurofilament light subunits (NFL) and neurofilament heavy subunits (NFH) as well as CSF levels of total tau (t-tau) and phosphorylated tau (p-tau) proteins were determined using ELISA in 20 Alzheimer's disease patients (AD group), 13 patients with other dementias (OD group), 17 patients with inflammatory aseptic neuro-infections (IP), and 20 aged-matched cognitively normal elderly persons (NC group).
The ratio CSF p-tau/t-tau was significantly higher in the NC group than that in the AD or OD groups (P<0.0005 for each group). The CSF NFH/p-tau and CSF NFL/p-tau ratios were significantly lower in AD patients than OD patients (P≤0.003). Serum and CSF NFL and CSF NFH levels were significantly higher in OD patients than AD patients (P≤0.03). The lowest values of the CSF NFL/NFH ratio were found in the IP group and they significantly differed from those in normal controls (P<0.0001) and any dementia group (IP vs. AD P<0.0001; IP vs. OD P=0.03).
CSF tau proteins and their index differentiated between AD or OD patients and cognitively normal subjects, while CSF levels of neurofilaments expressed as their index seem to contribute to the discrimination between patients with neuroinflammation and normal controls or AD patients.
To evaluate changes in the expression of clock genes and melatonin levels in patients with idiopathic REM sleep behavior disorder (RBD) as a potential early stage of synucleinopathies.
We assessed ...the rhythmicity of circadian clock genes using real time-quantitative polymerase chain reaction and 24-h blood melatonin profiles using radio-immunoassay in 10 RBD patients and nine age-matched controls.
The RBD patients did not show circadian rhythmicity for clock genes Per2, Bmal1, and Nr1d1 but the rhythmicity of Per 1 remained, and the amplitude of Per3 was diminished. The 24-h melatonin rhythm did not differ between RBD patients and healthy control subjects. Melatonin profile in RBD patients was delayed by 2 h compared to controls, the habitual sleep phases were phase delayed by about 1 h, however no phase shift occurred in any of the clock genes studied. The control group had stable acrophases of melatonin rhythms of approximately 5 h whereas the RBD patients had a more dispersed range over 11 h.
Our results suggest that RBD could be associated with altered expression of clock genes and delayed melatonin secretion. Thus, we argue that circadian system dysregulation could play a role in RBD.
•Data suggest that RBD could be associated with altered expression of clock genes and delayed melatonin secretion.•Circadian system dysregulation could play a role in RBD.
Tau protein in cerebrospinal fluid (CSF) is an important biomarker of Alzheimer's disease and some other brain diseases. Enzyme-linked immunosorbent assays (ELISAs) have been mostly used for ...quantification of tau and other biomarkers in CSF. However, these assays do not have sufficient sensitivity and dynamic range. In this study we tested the suitability of gold nanoparticles functionalized with tau-specific monoclonal antibody and oligonucleotide template for immuno-polymerase chain reaction (Nano-iPCR) quantification of tau protein in human CSF samples and compared it with ELISA, either commercial or newly developed with tyramide signal amplification. Our data indicate that Nano-iPCR is superior in sensitivity and detection range to ELISA in tau protein detection.
Background
Two unique very brief tests are easily administered and cognitively demanding. The Amnesia Light and Brief Assessment (abbreviated from the initial letters as ALBA) lasting 3 minutes and ...the door PICture Naming and Immediate Recall (PICNIR) lasting 4 minutes were validated and compared with the seven times longer Addenbrooke’s Cognitive Examination III (ACE‐III) (20‐30 minutes).
Methods
The ALBA, PICNIR and ACE‐III were administered to 155 elderly individuals in 2 groups comprising 40 patients with neurocognitive disorders according to DSM‐5 criteria and 116 normal elderly adults. The ALBA was evaluated using the memory ALBA score (MAS). The PICNIR was assessed using numbers of naming errors (NE) and correctly recalled picture names (PICR).
Results
All the tests were significantly different between the two age‐ and education matched groups (ACE‐III: 73±11 vs. 96±4 points) and showed excellent accuracy as assessed by the area under the ROC Curve (AUC): 0.89 for MAS, 0.81 for NE, 0.96 for PICR and 0.98 for the ACE‐III. The AUCs of PICR and ACE‐III were comparable and larger than those of MAS and NE. The ACE‐III strongly correlated with MAS and PICR (0.8, R2 = 60% each) and NE (‐0.7, R2 = 48%) in the whole sample.
Conclusions
The innovative and efficient ALBA and PICNIR tests have high discriminant validity for cognitive impairment and high convergent validity with the ACE‐III. Moreover, they can reliably predict total ACE‐III scores. Brevity and simple administration and evaluation are major advantages of the ALBA and the PICNIR over much longer ACE‐III for busy clinical practice.
Supported by grant COOPERATIO Neuroscience, Charles University, GAUK 268321 a SVV 260599 and grant NU20‐07‐00100.
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