OBJECTIVE: Dispersion is a form of intra-individual variability across neuropsychological tests that has been shown to predict cognitive decline. However, few studies have investigated the stability and predictive utility of both across- and within-domain dispersion. The current study aims to fill these gaps in the literature by examining multiple indices of dispersion in a longitudinal clinical sample of individuals diagnosed with mild cognitive impairment (MCI) at baseline.
METHODS: Two hundred thirty-eight MCI patients from a cognitive disorders clinic underwent testing at baseline and after approximately 1.5 years. Linear regression was used to examine whether baseline across- and within-domain dispersion predicted cognitive decline in individuals whose diagnostic classification progressed to dementia (i.e., MCI-Decline) and those who retained an MCI diagnosis at follow-up (i.e., MCI-Stable). Cognitive decline was operationalized dichotomously using group status and continuously using standardized regression-based (SRB) z-scores.
RESULTS: Dispersion variables at baseline and follow-up were positively correlated in both groups, with the exception of within-domain executive functioning and language dispersion in the MCI-Decline group. None of the dispersion variables predicted diagnostic conversion to MCI. Using SRB z-scores, greater across-domain dispersion predicted greater overall cognitive decline at follow-up, but this was not the case for within-domain variables with the exception of visuospatial skills.
CONCLUSIONS: Results suggest that across- and within-domain dispersion are relatively stable across time, and that across-domain dispersion is predictive of subtle cognitive decline in patients with MCI. However, these results also highlight that findings may differ based on the tests included in dispersion calculations.

BACKGROUND: Emerging and advanced technologies in the field of Artificial Intelligence (AI) represent promising methods to predict and diagnose neurodegenerative diseases, such as dementia. By using multimodal approaches, Machine Learning (ML) seems to provide a better understanding of the pathological mechanisms underlying the onset of dementia. The purpose of this review was to discuss the current ML application in the field of neuropsychology and electrophysiology, exploring its results in both prediction and diagnosis for different forms of dementia, such as Alzheimer\'s disease (AD), Vascular Dementia (VaD), Dementia with Lewy bodies (DLB), and Frontotemporal Dementia (FTD).
METHODS: Main ML-based papers focusing on neuropsychological assessments and electroencephalogram (EEG) studies were analyzed for each type of dementia.
RESULTS: An accuracy ranging between 70-90% or even more was observed in all neurophysiological and electrophysiological results trained by ML. Among all forms of dementia, the most significant findings were observed for AD. Relevant results were mostly related to diagnosis rather than prediction, because of the lack of longitudinal studies with appropriate follow-up duration. However, it remains unclear which ML algorithm performs better in diagnosing or predicting dementia.
CONCLUSIONS: Neuropsychological and electrophysiological measurements, together with ML analysis, may be considered as reliable instruments for early detection of dementia.

With the global increase in life expectancy, there has been a rise in the incidence of cognitive impairments attributed to diverse etiologies. Notably, approximately 50% of individuals diagnosed with mild cognitive impairment (MCI) progress to dementia within 3 years. However, the precise mechanisms underlying MCI remain elusive. Therefore, this study aimed to elucidate potential mechanisms implicated in MCI utilizing Per2 knockout (KO) mice, which have previously been shown to have cognitive deficits. Behavioral (Y-maze, Barnes maze) and molecular (electrophysiology, RNA sequencing, western blot, and immunofluorescence) experiments were conducted in Per2 KO and wild-type (WT) mice. Per2 KO mice exhibited impaired spatial working memory in the Y-maze and Barnes maze. However, there were no significant group differences in hippocampal long-term potentiation (LTP) between Per2 KO and WT mice, whereas striatal LTP in Per2 KO mice was lower compared to WT mice. In RNA sequencing analysis, 58 genes were downregulated and 64 genes were upregulated in the striatum of Per2 KO mice compared to WT mice. Among the differentially expressed genes, four genes (Chrm2, EphB2, Htr1b, Oprm1) were identified. Optimal expression levels of EPHB2 and OPRM1 were found to significantly enhance cognitive performance in mice. Additionally, Per2 KO mice exhibited reduced EPHB2-NMDAR-LTP and OPRM-mTOR signaling, along with elevated amyloid beta (Aβ) levels, when compared to WT mice. However, these alterations were reversed upon administration of morphine treatment. Striatal OPRM1-mTOR signaling, EPHB2-NMDAR-LTP signaling, and Aβ expression levels may exert a combined effect on MCI under the control of Per2 expression.

BACKGROUND: Despite parallel research indicating amyloid-β accumulation, alterations in cortical neurophysiological signaling, and multi-system neurotransmitter disruptions in Alzheimer\'s disease (AD), the relationships between these phenomena remains unclear.
METHODS: Using magnetoencephalography, positron emission tomography, and an atlas of 19 neurotransmitters, we studied the alignment between neurophysiological alterations, amyloid-β deposition, and the neurochemical gradients of the cortex.
RESULTS: In patients with mild cognitive impairment and AD, changes in cortical rhythms were topographically aligned with cholinergic, serotonergic, and dopaminergic systems. These alignments correlated with the severity of clinical impairments. Additionally, cortical amyloid-β plaques were preferentially deposited along neurochemical boundaries, influencing how neurophysiological alterations align with muscarinic acetylcholine receptors. Most of the amyloid-β-neurochemical and alpha-band neuro-physio-chemical alignments replicated in an independent dataset of individuals with asymptomatic amyloid-β accumulation.
CONCLUSIONS: Our findings demonstrate that AD pathology aligns topographically with the cortical distribution of chemical neuromodulator systems and scales with clinical severity, with implications for potential pharmacotherapeutic pathways.
CONCLUSIONS: Changes in cortical rhythms in Alzheimer\'s are organized along neurochemical boundaries. The strength of these alignments is related to clinical symptom severity. Deposition of amyloid-β (Aβ) is aligned with similar neurotransmitter systems. Aβ deposition mediates the alignment of beta rhythms with cholinergic systems. Most alignments replicate in participants with pre-clinical Alzheimer\'s pathology.

UNASSIGNED: Studies that assess cognition prospectively and study in detail anxiety history in the participants\' medical records within the context of brain aging and Alzheimer\'s disease are limited.
UNASSIGNED: To examine the associations of anxiety and unspecified emotional distress (UED) acquired throughout a person\'s life with prospectively collected cognitive outcomes.
UNASSIGNED: Mayo Clinic Study of Aging participants who were cognitively unimpaired at baseline were included. Anxiety and UED data were abstracted from the medical record using the Rochester Epidemiology Project (REP) resources and were run separately as predictors in our models. The data were analyzed using Cox proportional hazards models for the outcomes of incident mild cognitive impairment (MCI) and dementia and using linear mixed effects models for the outcomes of global and domain specific cognitive z-scores and included key covariates.
UNASSIGNED: The study sample (n = 1,808) had a mean (standard deviation) age of 74.5 (7.3) years and 51.4% were male. Anxiety was associated with increased risk of MCI and dementia and was associated with lower baseline cognitive z-scores and accelerated decline over time in the global, memory, and attention domains. UED was associated with faster decline in all domains except visuospatial but did not show evidence of association with incident cognitive outcomes. These results varied by medication use and timing of anxiety.
UNASSIGNED: Anxiety and UED both showed inverse associations with cognition. Utilization of anxiety and UED data from across the life course, as available, from the REP system adds robustness to our results.

UNASSIGNED: Conventional normative samples include individuals with undetected Alzheimer\'s disease neuropathology, lowering test sensitivity for cognitive impairment.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

UNASSIGNED: Findings from language sample analyses can provide efficient and effective indicators of cognitive impairment in older adults.
UNASSIGNED: This study used newly automated core lexicon analyses of Cookie Theft picture descriptions to assess differences in typical use across three groups.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

The emergence of sustained neuropsychiatric symptoms (NPS) among non-demented individuals in later life, defined as mild behavioral impairment (MBI), is linked to a higher risk of cognitive decline. However, the underlying pathophysiological mechanisms remain largely unexplored. A growing body of evidence has shown that MBI is associated with alterations in structural and functional neuroimaging studies, higher genetic predisposition to clinical diagnosis of Alzheimer\'s disease (AD), as well as amyloid and tau pathology assessed in the blood, cerebrospinal fluid, positron-emission tomography (PET) imaging and neuropathological examination. These findings shed more light on the MBI-related potential neurobiological mechanisms, paving the way for the development of targeted pharmacological approaches. In this review, we aim to discuss the available clinical evidence on the role of amyloid and tau pathology in MBI and the potential underlying pathophysiological mechanisms. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, disruption of neurotrophic factors, such as the brain-derived neurotrophic factor (BDNF), abnormal neuroinflammatory responses including the kynurenine pathway, dysregulation of transforming growth factor beta (TGF-β1), epigenetic alterations including micro-RNA (miR)-451a and miR-455-3p, synaptic dysfunction, imbalance in neurotransmitters including acetylcholine, dopamine, serotonin, gamma-aminobutyric acid (GABA) and norepinephrine, as well as altered locus coeruleus (LC) integrity are some of the potential mechanisms connecting MBI with amyloid and tau pathology. The elucidation of the underlying neurobiology of MBI would facilitate the design and efficacy of relative clinical trials, especially towards amyloid- or tau-related pathways. In addition, we provide insights for future research into our deeper understanding of its underlying pathophysiology of MBI, and discuss relative therapeutic implications.

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.