Effectiveness of dairy products to protect against cognitive decline in later life: a narrative review.

As the world's population ages the prevalence of age-related health concerns is increasing, including neurodegeneration disorders such as mild cognitive impairment, vascular dementia and Alzheimer's disease. Diet is a key modifiable risk factor for the development of neurodegeneration, likely due to gut-brain axis interactions related to neuroinflammation. Analyses of dietary patterns identified dairy as being part of a cognitively healthy diet; however, its contribution to cognitive outcomes is difficult to discern. This narrative review evaluates the literature to determine whether there is sufficient evidence that the consumption of dairy products helps to maintain cognitive function in later life. A search using the terms (dairy OR milk OR cheese OR yogurt OR yogurt) AND ("mild cognitive impairment" OR dementia OR "Alzheimer's disease") identified 796 articles. After screening and sorting, 23 observational studies and 6 intervention studies were identified. The results of the observational studies implied that the relationship between total dairy consumption and cognitive outcomes is inverse U-shaped, with moderate consumption (1-2 servings per day) being the most beneficial. The analysis of the intake of different types of dairy products indicated that fermented products, particularly cheese, were most likely responsible for the observed benefits. The experimental studies all used dairy-derived peptides produced during fermentation as the dietary intervention, and the results indicated that these could be an effective treatment for early-stage cognitive impairment. Further experimental studies with whole dairy products, particularly fermented dairy, are needed to determine whether the regular consumption of these foods should be recommended to maximize the likelihood of healthy cognitive aging.

Effects of folic acid supplementation on cognitive function and inflammation in elderly patients with mild cognitive impairment: A systematic review and meta-analysis of randomized controlled trials.

OBJECT: The aim was to assess the effect of folic acid supplementation on cognitive function and inflammatory cytokines in elderly patients with mild cognitive impairment. METHODS: From its inception until February 2024, four databases including Web of Science were searched. Two researchers independently screened the literature, assessed the quality, extracted data, and conducted a meta-analysis using RevMan. RESULTS: The systematic review included seven studies (with a total of 1102 participants, mean age 65-80 years), seven of which were appropriate for meta-analysis. Although a small number of studies found relatively large heterogeneity, the majority of studies showed significant benefit from folic acid supplementation, including the FSIQ (823 individuals, standardized mean difference [SMD] = 8.36, 95 % confidence interval [CI] = 0.79 - 1.08), Arithmetic (823 individuals, SMD = 0.17, 95 % CI = -0.03-0.31), Information, SMD = 1.73, 95 % CI 0.41-3.05), Digit Span (823 individuals, SMD = 0.17, 95 % CI = -0.03 - 0.31), Block Design (823 individuals, SMD = 0.26, 95 % CI 0.03-0.49), Picture Completion (823 individuals, SMD = 0.27, 95 % CI = -0.15 - 0.69) and Picture Arrangement (823 individuals, SMD = -0.12, 95 % CI = -0.26 - 0.01). Finally, folic acid supplementation had a significant effect on the reduction of most inflammatory cytokines, blood biomarkers of Alzheimer's disease, and Hcy. CONCLUSIONS: Folic acid supplementation seems to have a positive impact on cognitive function in older adults with mild cognitive impairment, but further evidence of its effectiveness in improving inflammatory cytokines is needed from high-quality studies.

Prevalence of sleep disturbances in people with mild cognitive impairment: A systematic review and meta-analysis.

This review was performed to determine sleep disturbance prevalence in individuals with mild cognitive impairment (MCI). The MEDLINE, Embase, Cochrane Library, CINAHL, PsycINFO, and Web of Science databases were systematically searched from inception to January 20, 2024. Fifty-two studies fulfilling the eligibility criteria were included. However, six of these studies were excluded from data synthesis due to poor methodological quality. The subjective sleep disturbance prevalence among all individuals with MCI was 35.8 % (95 % CI: 31.9-39.7) across 44 studies, and the objective sleep disturbance prevalence was 46.3 % (95 % CI: 36.3-56.3) across 6 studies. Five studies examined TST and WASO, while three assessed SE. Among all potential objective assessments of sleep disturbance prevalence, only TST, WASO, and SE could be meta-analyzed in MCI because of the limited number of studies available. The estimated sleep disturbance prevalence differed significantly according to measurement method, geographical region, and research design. However, the data source did not significantly influence prevalence estimates. In meta-regression analysis, publication year, participant age, percentage of females, and study quality did not predict prevalence. As subjective and objective sleep disturbances are common in people with MCI, effective intervention strategies should be developed to alleviate them.

Association of dual task gait performance with cognitive outcomes among older adults: Piloting an inexpensive, portable assessment platform.

Motor assessment has emerged as complementary evidence for the detection of late life cognitive disorders. Clinicians lack inexpensive, accurate, and portable tools for this purpose. To fill this void, the current study piloted measures from the Mizzou Point-of-care Assessment System a multimodal sensor platform. We examined the ability of these motor function measures to distinguish neurocognitive status and assessed their associations with cognitive performance. Data came from 42 older adults, including 16 with mild cognitive impairment (MCI). Participants performed dual task gait, pairing walking with serial subtraction by sevens, along with aa neuropsychological test battery. T-tests revealed that individuals with MCI demonstrated slower stride times (d = .55) and shorter stride lengths (d = .98) compared to healthy older adults. Results from hierarchical regression showed that stride time and stride length predicted cognitive performance across several domains, after controlling for cognitive status and demographics. Cognitive status moderated this relationship for global cognition and attention, wherein gait measures were significantly related to these outcomes for the cognitively normal group, but not the MCI group. Evidence from the current study provided preliminary support that MPASS measures demonstrate expected associations with cognitive performance and can distinguish amongst those with and without cognitive impairment.

Effectiveness of a mobile application for independent computerized cognitive training in patients with mild cognitive impairment: study protocol for the NeNaE Study, a randomized controlled trial.

BACKGROUND: Mild cognitive impairment (MCI) involves cognitive decline beyond typical age-related changes, but without significant daily activity disruption. It can encompass various cognitive domains as the causes of MCI are diverse. MCI as well as frequent comorbid neuropsychiatric conditions like depression and anxiety affect individuals' quality of life. Early interventions are essential, and computerized cognitive training (cCT) is an established treatment method. This paper presents the protocol for the NeuroNation MED Effectiveness Study, evaluating the self-administered mobile cCT intervention ("NeuroNation MED") in individuals with MCI to assess training effects on cognitive domains, health competence, neuropsychiatric symptoms, psychological well-being, and the general application usability. METHODS: This study protocol presents a single-blinded multicenter randomized controlled trial that will be carried out in six study centers in Germany and Luxembourg. We included adults with MCI (existing F06.7 ICD-10-GM diagnosis and TICS ≥ 21 and ≤ 32). The intervention group will use a mobile, multi-domain cCT ("NeuroNation MED") for 12 weeks. Meanwhile, the wait list control group will receive standard medical care or no care. The eligibility of volunteers will be determined through a telephone screening. After completion of the baseline examination, patients will be randomly assigned to one of the experimental conditions in a 2:1 ratio. In total, 286 participants will be included in this study. The primary outcome is the change of cognitive performance measured by the index score of the screening module of the Neuropsychological Assessment Battery. Secondary outcomes are changes in the Cognitive Failures Questionnaire, Hospital Anxiety and Depression Scale, Health-49, Health Literacy Questionnaire, among others. All of the primary and secondary outcomes will be assessed at baseline and after the 12-week post-allocation period. Furthermore, the intervention group will undergo an assessment of the System Usability Scale, and the training data of the NeuroNation MED application will be analyzed. DISCUSSION: This study aims to assess the effectiveness of a mobile self-administered cCT in enhancing cognitive abilities among individuals diagnosed with MCI. Should the findings confirm the effectiveness of the NeuroNation MED app, it may confer possible benefits for the care management of patients with MCI, owing to the accessibility, cost-effectiveness, and home-based setting it provides. Specifically, the cCT program could provide patients with personalized cognitive training, educational resources, and relaxation techniques, enabling participants to independently engage in cognitive training sessions at home without further supervision. TRIAL REGISTRATION: German Clinical Trials Register DRKS00025133. Registered on November 5, 2021.

Obstructive Sleep Apnea Among Patients with Mild Cognitive Impairment.

Background: Obstructive sleep apnea (OSA) is associated with cognitive disorders, but little is known about prevalence of co-occurring OSA and mild cognitive impairment (MCI) as well as about co-occurring OSA and Alzheimer's disease (AD). Pathophysiological models integrating OSA, cognitive deficits and neurodegeneration remain speculative. Findings in this area could contribute to the knowledge about pathophysiological processes in cognitive disorders and neurodegenerative processes, be helpful for the diagnosis of cognitive disorders and provide approaches for the treatment of cognitive disorders. Objective: Examining the prevalence of OSA and patterns of cognitive deficits as well as AD biomarker profiles associated with OSA in a cohort of 104 MCI patients. Methods: Assessments used include: respiratory polygraphy, The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD NB), Tau, phosphoTau181, amyloid-ß-1-42/1-40, 18F-fluorodeoxyglucose positron emission tomography (F18-FDG-PET). Results: Prevalence of OSA of any severity: 58,7% (Apnea Hypopnea Index (AHI)≥5/h), OSA in a moderate-to-severe extent (AHI≥15/h): 25%. Only 13.1% of MCI patients with OSA reported daytime sleepiness. MCI-OSA patients showed no specific neuropsychological pattern. Presence of OSA was not associated with specific AD biomarker profiles in the whole study group besides a positive association between AD positivity in an AD biomarker sub cohort. Conclusions: OSA is highly prevalent in patients with MCI. It might often remain undiagnosed as only a small number of MCI-OSA patients report daytime sleepiness. OSA could contribute to MCI symptoms and even to AD pathology. Further research is needed to validate these findings and to investigate possible pathophysiological relationships between OSA and MCI as well as between OSA and AD.

Embodied Spatial Navigation Training in Mild Cognitive Impairment: A Proof-of-Concept Trial.

Background: Egocentric and allocentric spatial memory impairments affect the navigation abilities of older adults with mild cognitive impairment (MCI). Embodied cognition research hints that specific aids can be implemented into virtual reality (VR) training to enhance spatial memory. Objective: In this study, we preliminarily tested 'ANTaging', an embodied-based immersive VR training for egocentric and allocentric memory, compared to treatment as usual (TAU) spatial training in MCI. Methods: MCI patients were recruited for this controlled trial. A cognitive battery was administered at pre-test, after ten sessions of ANTaging or TAU intervention, and at 3-month follow-up (FU). The primary outcomes were spatial cognition tests (Corsi supra-span, CSS; Manikin test, MT). VR egocentric and allocentric performance was also collected. Results: We found that ANTaging significantly improved MT scores at FU compared to TAU. CSS slightly improved in both groups. Concerning secondary outcomes, auditory-verbal forgetting significantly improved at post-test in the ANTaging but not TAU group and significantly declined at FU in the TAU but not in the ANTaging group. Global cognition significantly improved at FU for TAU and remained stable for ANTaging. Other tests showed no improvement or deterioration. Clinical significance showed that ANTaging is effective for CSS. Virtual egocentric and allocentric memory performance improved across ANTaging sessions. Conclusions: ANTaging holds the potential to be superior for improving spatial cognition in MCI compared to TAU. Embodied cognition research provides insights for designing effective spatial navigation rehabilitation in aging.

Mild cognitive impairment and microbiota: what is known and future perspectives.

Mild cognitive impairment (MCI) is a heterogeneous condition definable as the intermediate clinical state between normal aging and dementia. As a pre-dementia condition, there is a recent growing interest in the identification of non-invasive markers able to predict the progression from MCI to a more advanced stage of the disease. Previous evidence showed the close link between gut microbiota and neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). Conversely, the actual relationship between gut microbiota and MCI is yet to be clarified. In this work, we provide an overview about the current knowledge regarding the role of gut microbiota in the context of MCI, also assessing the potential for microbiota-targeted therapies. Through the review of the most recent studies focusing on this topic, we found evidence of an increase of Bacteroidetes at phylum level and Bacteroides at genus level in MCI subjects with respect to healthy controls and patients with AD. Despite such initial evidence, the definitive identification of a typical microbiota profile associated with MCI is still far from being achieved. These preliminary results, however, are growingly encouraging research on the role of gut microbiota modulation in improving the cognitive status of pre-dementia subjects. To date, few studies evaluated the role of probiotics in MCI subjects, and they showed favorable results, although still biased by small sample size, heterogeneity of study design and short follow-up.

Prolonged ventricular repolarization associated with mild cognitive impairment and white matter hyperintensities: a cross-sectional study.

Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen's criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p < 0.05). In the MRI subsample, QT, QTc, JT, and JTc intervals were significantly associated with larger total WMH and PWMH volumes (p < 0.05), but not with DWMH volume. Statistical interactions were detected, such that prolonged QT and JT intervals were significantly associated with reduced GM volume only among participants with coronary heart disease or without APOE ε4 allele (p < 0.05). Prolonged ventricular repolarization is associated with MCI and cerebral microvascular lesions in a general population of older adults. This underlies the importance of cognitive assessments and brain MRI examination among older adults with prolonged QT interval.

Choroid plexus volumes and auditory verbal learning scores are associated with conversion from mild cognitive impairment to Alzheimer's disease.

PURPOSE: Mild cognitive impairment (MCI) can be the prodromal phase of Alzheimer's disease (AD) where appropriate intervention might prevent or delay conversion to AD. Given this, there has been increasing interest in using magnetic resonance imaging (MRI) and neuropsychological testing to predict conversion from MCI to AD. Recent evidence suggests that the choroid plexus (ChP), neural substrates implicated in brain clearance, undergo volumetric changes in MCI and AD. Whether the ChP is involved in memory changes observed in MCI and can be used to predict conversion from MCI to AD has not been explored. METHOD: The current study used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to investigate whether later progression from MCI to AD (progressive MCI [pMCI], n = 115) or stable MCI (sMCI, n = 338) was associated with memory scores using the Rey Auditory Verbal Learning Test (RAVLT) and ChP volumes as calculated from MRI. Classification analyses identifying pMCI or sMCI group membership were performed to compare the predictive ability of the RAVLT and ChP volumes. FINDING: The results indicated a significant difference between pMCI and sMCI groups for right ChP volume, with the pMCI group showing significantly larger right ChP volume (p = .01, 95% confidence interval [-.116, -.015]). A significant linear relationship between the RAVLT scores and right ChP volume was found across all participants, but not for the two groups separately. Classification analyses showed that a combination of left ChP volume and auditory verbal learning scores resulted in the most accurate classification performance, with group membership accurately predicted for 72% of the testing data. CONCLUSION: These results suggest that volumetric ChP changes appear to occur before the onset of AD and might provide value in predicting conversion from MCI to AD.

Effect of combined physical-cognitive training on the functional and cognitive capacity of older people with mild cognitive impairment: a randomized controlled trial.

BACKGROUND: The increase in population aging highlights the growing prevalence of mild cognitive impairment, prompting the adoption of interventions that combine physical exercise and cognitive training to improve health and cognitive performance in older adults. The aim of this study was to analyze the efficacy of a combined program on physical and cognitive health in older people with cognitive impairment. METHODS: A 12-week randomized controlled clinical trial involving 95 participants (aged 72.12 ± 4.25 years), 47 individuals participated in a control group (CG) that only underwent cognitive stimulation, while 48 individuals were in an experimental group (EG) that participated in a combined program. Balance was measured using the Tinetti scale, upper body strength was assessed with the arm curl test, lower body strength was evaluated with the 30-s chair stand test, flexibility was tested using the back scratch test and chair sit-and-reach test, physical function was measured with the Timed Up and Go test, cognitive function was assessed using the Mini Mental State Examination, cognitive impairment was evaluated with the Montreal Cognitive Assessment, verbal fluency was tested with the Isaac test, and executive functions were assessed using the Trail Making Test. RESULTS: The results of the study show significant improvements in both physical and cognitive aspects, such as balance, gait, upper and lower body strength, flexibility, physical function, cognitive function, cognitive impairment, verbal fluency, and executive functions in the group that carried out the intervention compared to the control group. CONCLUSION: A combined program for older individuals with mild cognitive impairment leads to enhancements in physical and cognitive health. These improvements underscore the importance of integrating physical exercise with cognitive training as an effective strategy for enhancing overall health and quality of life in older adults. TRIAL REGISTRATION: NCT05503641.

The effects of different types of exercises on cognition in older persons with mild cognitive impairment: A systematic review and meta-analysis.

PURPOSE: This systematic review with meta-analysis aims to analyze the effects of different types of exercise on cognition, neuroprotective and neuroinflammatory blood markers in older adults with mild cognitive impairment (MCI). METHODS: Relevant studies were identified using PubMED, SPORTDiscuss, Web of Science, Scopus, and PsycInfo databases. Methodological quality assessment of the studies was done with modified Downs and Black checklist. Data obtained from the included studies was analyzed using Comprehensive Meta-Analysis 4.0 software and results were reported using the random effects method. RESULTS: A total of twenty-three studies were identified. The findings were summarized as change in cognitive function after the exercise interventions in general and after each type of exercise. On average, the exercise intervention revealed an effect size (ES): 1.165; 0.741 to 1.589 (95% Confidence Interval (CI); p < 0.001); aerobic exercise ES: 1.442; 0.624 to 2.260 (95 %CI); p = 0.001; Multimodal ES: 0,856; 0.366 to 1.346 (95 % CI); p = 0.001 and resistance exercise ES: 1.229; 0.339 to 2.120 (95 % CI); p = 0.007. In addition, we observed significant small ES: -0.475; -0.817 to -0.134 (95 %CI); p = 0.006, I2= 0 %; τ2 = 0 of exercise effects on Tumor Necrosis Factor-α (TNF-α) and non-significant large ES:0.952; -0.238 to 2.142 (95 %CI); p = 0.117 on Brain Derived Neurotrophic Factor (BDNF) in persons with MCI. CONCLUSION: The present study revealed the existence of a large positive effect of overall exercise intervention on cognitive function and a small effect on TNF-α in old people with MCI. Additionally, this study demonstrates that aerobic and resistance exercises had similar larger positive effects and were better than multimodal exercise on increasing cognition in older persons with MCI.

Compared to exercise, the effects of exercise combined with cognitive training in people with mild cognitive impairment: a network meta-analysis.

OBJECTIVES: The study aimed to evaluate the relative effectiveness of exercise combined with cognitive training (E&CT) in improving cognitive function compared to exercise alone. METHOD: PubMed, Embase, Cochrane Central Register of Controlled Trials, SPORTDiscus, and OpenGrey were systematically searched. Additional screenings were performed by reviewing citations of relevant articles. Studies were included if they met inclusion criteria. Both pairwise and network meta-analyses were performed using a random effects model in Stata 15.0. RESULTS: Totally, 46 trials from 54 literature (n = 2846) were eligible for inclusion in the meta-analysis. The network meta-analysis indicated that exercise alone was more efficacious than E&CT in improving global cognition and multicomponent exercise exhibited the highest likelihood (SUCRA value= 89.0%) of being the most effective type. Regarding memory function, E&CT presented greater potential than exercise alone, with the interactive modality ranking first (SUCRA value = 88.4%). Multicomponent exercise was identified as the top intervention for enhancing executive function. The overall quality of the included studies was rated as moderate, and the certainty of evidence ranged from low to high. CONCLUSION: Multicomponent exercise emerged as the optimal intervention for improving global cognition and executive function. Nevertheless, for memory function, the interactive modality of E&CT demonstrated the highest probability of being the most effective choice.

Detection of cerebrospinal fluid biomarkers changes of Alzheimer's disease using a cognitive stress test in persons with subjective cognitive decline and mild cognitive impairment.

Introduction: Timely and accurate diagnosis of the earliest manifestations of Alzheimer's disease (AD) is critically important. Cognitive challenge tests such as the Loewenstein Acevedo Scales for Semantic Interference and Learning (LASSI-L) have shown favorable diagnostic properties in a number of previous investigations using amyloid or FDG PET. However, no studies have examined LASSI-L performance against cerebrospinal fluid biomarkers of AD, which can be affected before the distribution of fibrillar amyloid and other changes that can be observed in brain neuroimaging. Therefore, we aimed to evaluate the relationship between LASSI-L scores and CSF biomarkers and the capacity of the cognitive challenge test to detect the presence of amyloid and tau deposition in patients with subjective cognitive decline and amnestic mild cognitive impairment (MCI). Methods: One hundred and seventy-nine patients consulting for memory loss without functional impairment were enrolled. Patients were examined using comprehensive neuropsychological assessment, the LASSI-L, and cerebrospinal fluid (CSF) biomarkers (Aß1-42/Aß1-40 and ptau181). Means comparisons, correlations, effect sizes, and ROC curves were calculated. Results: LASSI-L scores were significantly associated with CSF biomarkers Aß1-42/Aß1-40 in patients diagnosed with MCI and subjective cognitive decline, especially those scores evaluating the capacity to recover from proactive semantic interference effects and delayed recall. A logistic regression model for the entire sample including LASSI-L and age showed an accuracy of 0.749 and an area under the curve of 0.785 to detect abnormal amyloid deposition. Conclusion: Our study supports the biological validity of the LASSI-L and its semantic interference paradigm in the context of the early stages of AD. These findings emphasize the utility and the convenience of including sensitive cognitive challenge tests in the assessment of patients with suspicion of early stages of AD.

Altered activation of the dorsal anterior cingulate cortex during oddball performance in individuals at risk for Alzheimer's disease.

INTRODUCTION: The neural mechanisms underlying neurodegenerative disorders in the elderly remain elusive, despite extensive neuroimaging research in recent decades. Amnestic type mild cognitive impairment (aMCI) and late-life major depressive disorder (MDD) are two such conditions characterized by intersecting cognitive and affective symptomatology, and they are at a higher risk for Alzheimer's disease. MATERIALS AND METHODS: This study analyzed the neural underpinnings of cognitive and depressive symptoms in a cohort comprising 12 aMCI subjects, 24 late-life MDD patients, and 26 healthy controls (HCs). Participants underwent a detailed neuropsychological assessment and completed a visual attentional oddball task during functional magnetic resonance imaging (fMRI), with evaluations at baseline and at 2-year follow-up. RESULTS: Initial findings showed that aMCI subjects had reduced dACC activation during oddball (target) stimulus detection, a pattern that persisted in longitudinal analyses and correlated with cognitive functioning measures. For HCs, subsequent dACC activation was linked to depression scores. Furthermore, in the affective-cognitive altered groups, later dACC activation correlated with oddball and memory performance. CONCLUSIONS: These findings enhance our comprehension of the neurobiological basis of cognitive and depressive disturbances in aging, indicating that dACC activation in response to a visual attentional oddball task could serve as a neural marker for assessing cognitive impairment and depression in conditions predisposing to Alzheimer's disease.

The long-term effect on oral health and quality of life using a powered toothbrush in individuals with mild cognitive impairment. An intervention trial.

BACKGROUND: The number of older individuals with mild cognitive impairment and neurocognitive diseases is increasing, which may rapidly deteriorate oral health and Quality of life. Therefore, removing dental biofilm is essential for maintaining good oral health. The present study aimed to investigate whether introducing a powered toothbrush reduces the presence of dental plaque, bleeding on probing, and periodontal pockets ≥4 mm, leading to maintained or improved oral health and improved Quality of life in a group of older individuals with mild cognitive impairment. METHODS: Two hundred and thirteen individuals aged 55 or older living without official home care with a Mini-Mental State Examination (MMSE) score between 20 and 28 and a history of memory problems in the previous 6 months were recruited and screened for the study. The individuals received a powered toothbrush and thorough instructions on how to use it. Clinical oral examinations, Quality of life examinations, and MMSE tests were conducted at baseline, 6, 12, and 24 months. The intervention group was compared to control groups at baseline and 24-month examination. It was divided into an MMSE high group with a score of more than 26 and an MMSE low group with a score of 26 and lower or decreasing two steps or more for 12 months. RESULTS: PI, BOP, and PPD≥4 mm improved continuously in both MMSE groups during the 24 months of the study. The values for QoL-AD deteriorated over time, while the oral health-related Quality of life did not show any statistically significant changes. CONCLUSIONS: Introducing a powered toothbrush improved PI, BOP, and PPD≥4 mm over 24 months, even among individuals with low or declining MMSE scores. Improved oral health is associated with a preserved OHR-QoL.

The Case of the Cookie Jar: Differences in Typical Language Use in Dementia.

Background: Findings from language sample analyses can provide efficient and effective indicators of cognitive impairment in older adults. Objective: This study used newly automated core lexicon analyses of Cookie Theft picture descriptions to assess differences in typical use across three groups. Methods: Participants included adults without diagnosed cognitive impairments (Control), adults diagnosed with Alzheimer's disease (ProbableAD), and adults diagnosed with mild cognitive impairment (MCI). Cookie Theft picture descriptions were transcribed and analyzed using CLAN. Results: Results showed that the ProbableAD group used significantly fewer core lexicon words overall than the MCI and Control groups. For core lexicon content words (nouns, verbs), however, both the MCI and ProbableAD groups produced significantly fewer words than the Control group. The groups did not differ in their use of core lexicon function words. The ProbableAD group was also slower to produce most of the core lexicon words than the MCI and Control groups. The MCI group was slower than the Control group for only two of the core lexicon content words. All groups mentioned a core lexicon word in the top left quadrant of the picture early in the description. The ProbableAD group was then significantly slower than the other groups to mention a core lexicon word in the other quadrants. Conclusions: This standard and simple-to-administer task reveals group differences in overall core lexicon scores and the amount of time until the speaker produces the key items. Clinicians and researchers can use these tools for both early assessment and measurement of change over time.

Sex-Specific Differences in Serum Kallikrein-8 (KLK8): An Exploratory Study.

Background: There are indications for sex-specific differences regarding the association between kallikrein-8 (KLK8) and cognitive impairment in early stages of Alzheimer's disease for which KLK8 may be an early blood-based biomarker. These may be due to different levels of sex hormones. To correctly interpret KLK8 blood concentrations, sex-specific analyses are needed. Objective: The aim of our exploratory study was to investigate sex-specific differences in blood-based KLK8 in participants of the population-based Heinz Nixdorf Recall study with different cognitive status and the association between KLK8 and sex hormones. Methods: In 290 participants (45% women, 69.7±7.4 years (mean±SD)) we investigated sex-specific serum KLK8 differences between cognitively unimpaired (CU, 43%) and cognitively impaired (CI) participants and the association between KLK8 and dehydroepiandrosteronsulfate (DHEAS), estradiol and testosterone, using adjusted multiple linear regression. Results: The mean±SD KLK8 was similar for CU men (808.1±729.6 pg/ml) and women (795.9±577.7 pg/ml); adjusted mean-difference [95%-CI]: -95.3 [-324.1;133.5] pg/ml. KLK8 was lower in CI women (783.5±498.7 pg/ml) than men (1048.4±829 pg/ml); -261 [-493.1; -29] pg/ml. In men but not women, there was a weak indication for a positive slope between estradiol (11.9 [-0.4;24.3] pg/ml) and DHEAS (1.4 [-0.5;3.3] pg/ml) with KLK8, while testosterone had no impact. Conclusions: The results suggested a different role for KLK8 in the development of cognitive impairment in men and women, potentially influenced by sex hormones. To use blood KLK8 as an early biomarker, further research on hormonal regulation of KLK8 expression is needed as a part of the investigation of the KLK8 involvement in cognitive impairment and Alzheimer's disease pathology.

Associations Between Music and Dance Relationships, Rhythmic Proficiency, and Spatiotemporal Movement Modulation Ability in Adults with and without Mild Cognitive Impairment.

Background: Personalized dance-based movement therapies may improve cognitive and motor function in individuals with mild cognitive impairment (MCI), a precursor to Alzheimer's disease. While age- and MCI-related deficits reduce individuals' abilities to perform dance-like rhythmic movement sequences (RMS)-spatial and temporal modifications to movement-it remains unclear how individuals' relationships to dance and music affect their ability to perform RMS. Objective: Characterize associations between RMS performance and music or dance relationships, as well as the ability to perceive rhythm and meter (rhythmic proficiency) in adults with and without MCI. Methods: We used wearable inertial sensors to evaluate the ability of 12 young adults (YA; age = 23.9±4.2 years; 9F), 26 older adults without MCI (OA; age = 68.1±8.5 years; 16F), and 18 adults with MCI (MCI; age = 70.8±6.2 years; 10F) to accurately perform spatial, temporal, and spatiotemporal RMS. To quantify self-reported music and dance relationships and rhythmic proficiency, we developed Music (MRQ) and Dance Relationship Questionnaires (DRQ), and a rhythm assessment (RA), respectively. We correlated MRQ, DRQ, and RA scores against RMS performance for each group separately. Results: The OA and YA groups exhibited better MRQ and RA scores than the MCI group (p < 0.006). Better MRQ and RA scores were associated with better temporal RMS performance for only the YA and OA groups (r2 = 0.18-0.41; p < 0.045). DRQ scores were not associated with RMS performance in any group. Conclusions: Cognitive deficits in adults with MCI likely limit the extent to which music relationships or rhythmic proficiency improve the ability to perform temporal aspects of movements performed during dance-based therapies.

Mayo Normative Studies: Amyloid and Neurodegeneration Negative Normative Data for the Auditory Verbal Learning Test and Sex-Specific Sensitivity to Mild Cognitive Impairment/Dementia.

Background: Conventional normative samples include individuals with undetected Alzheimer's disease neuropathology, lowering test sensitivity for cognitive impairment. Objective: We developed Mayo Normative Studies (MNS) norms limited to individuals without elevated amyloid or neurodegeneration (A-N-) for Rey's Auditory Verbal Learning Test (AVLT). We compared these MNS A-N- norms in female, male, and total samples to conventional MNS norms with varying levels of demographic adjustments. Methods: The A-N- sample included 1,059 Mayo Clinic Study of Aging cognitively unimpaired (CU) participants living in Olmsted County, MN, who are predominantly non-Hispanic White. Using a regression-based approach correcting for age, sex, and education, we derived fully-adjusted T-score formulas for AVLT variables. We validated these A-N- norms in two independent samples of CU (n = 261) and mild cognitive impairment (MCI)/dementia participants (n = 392) > 55 years of age. Results: Variability associated with age decreased by almost half in the A-N- norm sample relative to the conventional norm sample. Fully-adjusted MNS A-N- norms showed approximately 7- 9% higher sensitivity to MCI/dementia compared to fully-adjusted MNS conventional norms for trials 1- 5 total and sum of trials. Among women, sensitivity to MCI/dementia increased with each normative data refinement. In contrast, age-adjusted conventional MNS norms showed greatest sensitivity to MCI/dementia in men. Conclusions: A-N- norms show some benefits over conventional normative approaches to MCI/dementia sensitivity, especially for women. We recommend using these MNS A-N- norms alongside MNS conventional norms. Future work is needed to determine if normative samples that are not well characterized clinically show greater benefit from biomarker-refined approaches.