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Background: Dementia is characterized by a cognitive decline in memory and other domains that lead to functional impairments. As people age, subjective memory complaints (SMC) become common, where individuals perceive cognitive decline without objective deficits on assessments. SMC can be an early sign and may precede amnestic mild cognitive impairment (MCI), which frequently advances to Alzheimer's disease (AD). Objective: This study aims to investigate white matter microstructure in individuals with SMC, in cognitively impaired (CI) cohorts, and in cognitively normal individuals using diffusion kurtosis imaging (DKI) and free water imaging (FWI). The study also explores voxel-based correlations between DKI/FWI metrics and cognitive scores to understand the relationship between brain microstructure and cognitive function. Methods: Twelve healthy controls (HCs), ten individuals with SMC, and eleven CI individuals (MCI or AD) were enrolled in this study. All participants underwent MRI 3T scan and the BNI Screen (BNIS) for Higher Cerebral Functions. Results: The mean kurtosis tensor and anisotropy of the kurtosis tensor showed significant differences across the three groups, indicating altered white matter microstructure in CI and SMC individuals. The free water volume fraction (f) also revealed group differences, suggesting changes in extracellular water content. Notably, these metrics effectively discriminated between the CI and HC/SMC groups. Additionally, correlations between imaging metrics and BNIS scores were found for CI and SMC groups. Conclusions: These imaging metrics hold promise in discriminating between individuals with CI and SMC. The observed differences indicate their potential as sensitive and specific biomarkers for early detection and differentiation of cognitive decline. [ABSTRACT FROM AUTHOR]

Introduction: Manual motor problems have been reported in mild cognitive impairment (MCI) and Alzheimer's disease (AD), but the specific aspects that are affected, their neuropathology, and potential value for classification modeling is unknown. The current study examined if multiple measures of motor strength, dexterity, and speed are affected in MCI and AD, related to AD biomarkers, and are able to classify MCI or AD. Methods: Fifty-three cognitively normal (CN), 33 amnestic MCI, and 28 AD subjects completed five manual motor measures: grip force, Trail Making Test A, spiral tracing, finger tapping, and a simulated feeding task. Analyses included (1) group differences in manual performance; (2) associations between manual function and AD biomarkers (PET amyloid β, hippocampal volume, and APOE ε4 alleles); and (3) group classification accuracy of manual motor function using machine learning. Results: Amnestic MCI and AD subjects exhibited slower psychomotor speed and AD subjects had weaker dominant hand grip strength than CN subjects. Performance on these measures was related to amyloid β deposition (both) and hippocampal volume (psychomotor speed only). Support vector classification well-discriminated control and AD subjects (area under the curve of 0.73 and 0.77, respectively) but poorly discriminated MCI from controls or AD. Conclusion: Grip strength and spiral tracing appear preserved, while psychomotor speed is affected in amnestic MCI and AD. The association of motor performance with amyloid β deposition and atrophy could indicate that this is due to amyloid deposition in and atrophy of motor brain regions, which generally occurs later in the disease process. The promising discriminatory abilities of manual motor measures for AD emphasize their value alongside other cognitive and motor assessment outcomes in classification and prediction models, as well as potential enrichment of outcome variables in AD clinical trials. [ABSTRACT FROM AUTHOR]

Background: Despite reports of gross motor problems in mild cognitive impairment (MCI) and Alzheimer's disease (AD), fine motor function has been relatively understudied. Objective: We examined if finger tapping is affected in AD, related to AD biomarkers, and able to classify MCI or AD. Methods: Forty-seven cognitively normal, 27 amnestic MCI, and 26 AD subjects completed unimanual and bimanual computerized tapping tests. We tested 1) group differences in tapping with permutation models; 2) associations between tapping and biomarkers (PET amyloid-β, hippocampal volume, and APOEɛ4 alleles) with linear regression; and 3) the predictive value of tapping for group classification using machine learning. Results: AD subjects had slower reaction time and larger speed variability than controls during all tapping conditions, except for dual tapping. MCI subjects performed worse than controls on reaction time and speed variability for dual and non-dominant hand tapping. Tapping speed and variability were related to hippocampal volume, but not to amyloid-β deposition or APOEɛ4 alleles. Random forest classification (overall accuracy = 70%) discriminated control and AD subjects, but poorly discriminated MCI from controls or AD. Conclusions: MCI and AD are linked to more variable finger tapping with slower reaction time. Associations between finger tapping and hippocampal volume, but not amyloidosis, suggest that tapping deficits are related to neuropathology that presents later during the disease. Considering that tapping performance is able to differentiate between control and AD subjects, it can offer a cost-efficient tool for augmenting existing AD biomarkers. [ABSTRACT FROM AUTHOR]

Hippocampal atrophy is a widely used biomarker for Alzheimer's disease (AD), but the cost, time, and contraindications associated with magnetic resonance imaging (MRI) limit its use. Recent work has shown that a low-cost upper extremity motor task has potential in identifying AD risk. Fifty-four older adults (15 cognitively unimpaired, 24 amnestic mild cognitive impairment, and 15 AD) completed six motor task trials and a structural MRI. Several measures of motor task performance significantly predicted bilateral hippocampal volume, controlling for age, sex, education, and memory. Thus, this motor task may be an affordable, non-invasive screen for AD risk and progression. [ABSTRACT FROM AUTHOR]

Cortical amyloid deposition is one of the hallmark biomarkers of Alzheimer's disease (AD). However, given how cost- and timeintensive amyloid imaging can be, there is a continued need for a low-cost, non-invasive, and accessible enrichment strategy to pre-screen individuals for their likelihood of amyloid prior to imaging. Previous work supports the use of coordinated limb movement as a potential screening tool, even after controlling for cognitive and daily function. Thirty-six patients diagnosed with amnestic mild cognitive impairment over the age of 65 underwent 18F-Flutemetamol amyloid-positron emission tomography (PET) imaging and then completed a timed motor task involving upper limb coordination. This task takes ∼5 minutes to administer and score. Multivariate linear regression and receiver operator characteristic analyses showed that including motor task performance improved model prediction of amyloid burden. Results support the rationale for including functional upper extremity motor assessment as a cost- and time-effective means to screen participants for amyloid deposition. [ABSTRACT FROM AUTHOR]

Affordable, noninvasive methods of predicting functional decline are needed for individuals at risk for Alzheimer's disease. This study tested whether a timed upper-extremity motor task predicted functional decline over one year in 79 adults diagnosed with amnestic mild cognitive impairment. Participants completed subjective and objective measures of daily functioning at baseline and one year later. Motor task performance and delayed memory were also evaluated at baseline. Motor task performance was a significant predictor of one-year follow-up daily functioning, improving model fits by 18- 35%. Thus, motor behavior has potential to be an affordable enrichment strategy that is sensitive to functional decline. [ABSTRACT FROM AUTHOR]

Practice effects on neuropsychological tests, which are improvements in test scores due to repeated exposure to testing materials, are robust in healthy elders, but muted in older adults with cognitive disorders. Conversely, few studies have investigated practice effects on motor tasks involving procedural memory, particularly across test–retest periods exceeding 24 hours. The current study examined one-week practice effects on a novel upper extremity motor task in 54 older adults with amnestic mild cognitive impairment. Results indicate that these individuals with primary memory deficits did improve on this motor task within a brief training session as well as across one week. These practice effects were unrelated to demographic characteristics or global cognition. One-week practice effects were, however, negatively related to delayed memory function, with larger practice effects being associated with poorer delayed memory and potentially better visuospatial ability. The presence of longer term practice effects on a procedural motor task not only has implications for how longitudinal assessments with similar measures involving implicit memory might be interpreted, but may also inform future rehabilitative strategies for patients with more severe declarative memory deficits. [ABSTRACT FROM PUBLISHER]

Practice effects are improvements on cognitive tests as a result of repeated exposure to testing material. However, variability exists in the literature about whether patients with amnestic mild cognitive impairment (MCI) display practice effects, which may be partially due to the methods used to calculate these changes on repeated tests. The purpose of the current study was to examine multiple methods of assessing short-term practice effects in 58 older adults with MCI. The cognitive battery, which included tests of memory (Hopkins Verbal Learning Test–Revised and Brief Visuospatial Memory Test–Revised) and processing speed (Symbol Digit Modalities Test and Trail Making Test Parts A and B), was administered twice across one week. Dependentttests showed statistically significant improvement on memory scores (ps < .01,ds = 0.8–1.3), but not on processing speed scores. Despite this, the sample showed no clinically meaningful improvement on any cognitive scores using three different reliable change indices. Regression-based change scores did identify relatively large groups of participants who showed smaller than expected practice effects, which may indicate that this method is more sensitive in identifying individuals who may portend a declining trajectory. Practice effects remain a complex construct, worthy of continued investigation in diverse clinical conditions. [ABSTRACT FROM AUTHOR]

The mechanisms linking motor function to Alzheimer's disease (AD) progression have not been well studied, despite evidence of AD pathology within motor brain regions. Thus, there is a need for new motor measure that is sensitive and specific to AD. In a sample of 121 older adults (54 cognitive unimpaired [CU], 35 amnestic Mild Cognitive Impairment [aMCI], and 32 probable mild AD), intrasubject standard deviation (ISD) across six trials of a novel upper-extremity motor task was predicted with volumetric regional gray matter and neuropsychological scores using classification and regression tree (CART) analyses. Both gray matter and neuropsychological CART models indicated that motor task ISD (our measure of motor learning) was related to cortical regions and cognitive test scores associated with memory, executive function, and visuospatial skills. CART models also accurately distinguished motor task ISD of MCI and probable mild AD from CU. Variability in motor task performance across practice trials may be valuable for understanding preclinical and early-stage AD. • Our motor learning test may help screen for Alzheimer's Disease (AD). • Data justify studying variability of a motor assessment across multiple attempts. • Classification and regression tree (CART) analyses are valuable for aging research. • Future research will validate motor task variability against AD biomarkers. [ABSTRACT FROM AUTHOR]