Normal Elderly Research Articles

Grammaticality Judgment and Error Correction Abilities in Normal Elderly

Grammaticality Judgment and Error Correction Abilities in Normal Elderly

SUBJECTIVE OLFACTORY FUNCTIONING: CORRELATES OF THE HYPOSMIA RATING SCALE IN NORMAL ELDERS

SUBJECTIVE OLFACTORY FUNCTIONING: CORRELATES OF THE HYPOSMIA RATING SCALE IN NORMAL ELDERS

AMYLOID LEVELS IN THE NORMAL RANGE ARE PREDICTIVE FOR INCIDENT DEMENTIA IN NON-DEMENTED ELDERLY

AMYLOID LEVELS IN THE NORMAL RANGE ARE PREDICTIVE FOR INCIDENT DEMENTIA IN NON-DEMENTED ELDERLY

DIFFERENTIAL INFLUENCE OF SEX HORMONES, GONADOTROPINS, AND SEX HORMONE BINDING GLOBULIN ON BRAIN AMYLOID BURDEN BETWEEN MALE AND FEMALE IN A COGNITIVELY NORMAL ELDERLY POPULATION

DIFFERENTIAL INFLUENCE OF SEX HORMONES, GONADOTROPINS, AND SEX HORMONE BINDING GLOBULIN ON BRAIN AMYLOID BURDEN BETWEEN MALE AND FEMALE IN A COGNITIVELY NORMAL ELDERLY POPULATION

Orexin-A is Associated with Increases in Cerebrospinal Fluid Phosphorylated-Tau in Cognitively Normal Elderly Subjects.

To evaluate the role of orexin-A with respect to cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers, and explore its relationship to cognition and sleep characteristics in a group of cognitively normal elderly individuals. Subjects were recruited from multiple community sources for National Institutes of Health supported studies on normal aging, sleep and CSF biomarkers. Sixty-three participants underwent home monitoring for sleep-disordered breathing, clinical, sleep and cognitive evaluations, as well as a lumbar puncture to obtain CSF. Individuals with medical history or with magnetic resonance imaging evidence of disorders that may affect brain structure or function were excluded. Correlation and linear regression analyses were used to assess the relationship between orexin-A and CSF AD-biomarkers controlling for potential sociodemographic and sleep confounders. Levels of orexin-A, amyloid beta 42 (Aβ42), phosphorylated-tau (P-Tau), total-tau (T-Tau), Apolipoprotein E4 status, age, years of education, reported total sleep time, number of awakenings, apnea-hypopnea indices (AHI), excessive daytime sleepiness, and a cognitive battery were analyzed. Subjects were 69.59 ± 8.55 years of age, 57.1% were female, and 30.2% were apolipoprotein E4+. Orexin-A was positively correlated with Aβ42, P-Tau, and T-Tau. The associations between orexin-A and the AD-biomarkers were driven mainly by the relationship between orexin-A and P-Tau and were not influenced by other clinical or sleep characteristics that were available. Orexin-A is associated with increased P-Tau in normal elderly individuals. Increases in orexin-A and P-Tau might be a consequence of the reduction in the proportion of the deeper, more restorative slow wave sleep and rapid eye movement sleep reported with aging. Clinicaltrials.gov registration number NCT01962779.

Effects of Noise Level and Cognitive Function on Speech Perception in Normal Elderly and Elderly with Amnestic Mild Cognitive Impairment.

Along with auditory function, cognitive function contributes to speech perception in the presence of background noise. Older adults with cognitive impairment might, therefore, have more difficulty perceiving speech-in-noise than their peers who have normal cognitive function. We compared the effects of noise level and cognitive function on speech perception in patients with amnestic mild cognitive impairment (aMCI), cognitively normal older adults, and cognitively normal younger adults. We studied 14 patients with aMCI and 14 age-, education-, and hearing threshold-matched cognitively intact older adults as experimental groups, and 14 younger adults as a control group. We assessed speech perception with monosyllabic word and sentence recognition tests at four noise levels: quiet condition and signal-to-noise ratio +5 dB, 0 dB, and -5 dB. We also evaluated the aMCI group with a neuropsychological assessment. Controlling for hearing thresholds, we found that the aMCI group scored significantly lower than both the older adults and the younger adults only when the noise level was high (signal-to-noise ratio -5 dB). At signal-to-noise ratio -5 dB, both older groups had significantly lower scores than the younger adults on the sentence recognition test. The aMCI group's sentence recognition performance was related to their executive function scores. Our findings suggest that patients with aMCI have more problems communicating in noisy situations in daily life than do their cognitively healthy peers and that older listeners with more difficulties understanding speech in noise should be considered for testing of neuropsychological function as well as hearing.

Differences in knowledge of dementia among older adults with normal cognition, mild cognitive impairment, and dementia: A representative nationwide sample of Korean elders

ObjectiveLack of knowledge about a disease could impede early diagnosis and may lead to delays in seeking appropriate medical care. The aim of this study was to explore knowledge of dementia (KOD) and to find the determinants of KOD among three groups: older adults with normal cognition, mild cognitive impairment (MCI), and dementia. MethodsA representative nationwide sample of 6141 Korean elders aged 65 years or older participated in face-to-face interviews and answered 14 questions pertaining to general information, etiology, symptoms, and treatment of dementia. Stepwise multiple regressions and path analyses probed the relationships between various sociodemographic variables and KOD. ResultsThe percentage of correct responses was only 62%. The item ‘A person who remembers things that happened in the past does not have dementia’ was answered correctly (false) by only 24.8–27% of the respondents in all groups. Older adults with normal cognition had higher KOD scores than those with MCI or dementia. In the normal-cognition group, KOD scores were higher among highly educated, younger, and literate women with no depression and a family history of dementia. In contrast with the determinants in the normal-cognition group, only the ability to read and write predicted KOD scores in the dementia group. ConclusionsEfforts to enhance KOD in elder adults are needed. Public education regarding the differences between dementia and healthy aging may increase KOD among normal elders and those with MCI. Among elders with dementia, educational materials that do not require literacy may be more helpful in increasing KOD with the aim of preventing treatment delay.

Incidental Cerebral Microbleeds and Cerebral Hypoperfusion in Cognitively Normal Elderly Individuals (S42.008)

Incidental Cerebral Microbleeds and Cerebral Hypoperfusion in Cognitively Normal Elderly Individuals (S42.008)

A Novel Cognitive Stress Test for the Detection of Preclinical Alzheimer Disease: Discriminative Properties and Relation to Amyloid Load

To examine the utility of a novel "cognitive stress test" to detect subtle cognitive impairments and amyloid load within the brains of neuropsychologically normal community-dwelling elders. Participants diagnosed as cognitively normal (CN), subjective memory impairment (SMI), mild cognitive impairment (MCI), and preclinical mild cognitive impairment (PreMCI) were administered the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), a sensitive test of proactive semantic interference (PSI), retroactive semantic interference, and, uniquely, the ability to recover from the effects of PSI. Ninety-three subjects (31 men and 62 women) were recruited from three academic institutions in a research consortium. A subset of these individuals underwent 18F florbetapir positron emission tomography scanning. Relative percentages of impairment for each diagnostic group on the LASSI-L were calculated by χ(2) and Fisher's exact tests. Spearman's rho was used to examine associations between amyloid load and different cognitive measures. LASSI-L deficits were identified among 89% of those with MCI, 47% with PreMCI, 33% with SMI, and 13% classified as CN. CN subjects had no difficulties with recovery from PSI, whereas SMI, preMCI, and MCI participants evidenced deficits in recovery from PSI effects. Among a subgroup of participants with normal scores on traditional neuropsychological tests, the strong associations were between the failure to recover from the effects of PSI and amyloid load in the brain. Failure to recover or compensate for the effects of PSI on the LASSI-L distinguishes the LASSI-L from other widely used neuropsychological tests and appears to be sensitive to subtle cognitive impairments and increasing amyloid load.

Novel CSF Biomarker of Metabolic Dysfunction Predicts AD‐like Associations across the Alzheimer's Spectrum

Obesity and insulin resistance(IR) are associated with brain atrophy and cognitive decline, particularly in Alzheimer's disease (AD). IR is correlated with temporal and frontal amyloid deposition and brain atrophy in late middle‐aged participants at risk for AD, as well as less glucose metabolism in cognitively normal elders and AD participants. Because insulin‐degrading enzyme complicates the measurement of insulin levels in cerebrospinal fluid (CSF), an alternative biomarker for metabolic dysregulation in CSF should be used to draw conclusions between central hyper insulinemia and associations with brain atrophy and hypometabolism. Ecto‐nucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), also known as autotaxin, is studied in tumor cell mobility and is produced by beige adipose tissue. ENPP2 regulates energy metabolism, and is higher in AD prefrontal cortex (PFC). Additionally, ENPP2 stimulates the formation of lysophosphatidic acid, which promotes the generation of tissue fibrosis in vivo and in vitro. We studied Alzheimer's Disease Neuroimaging Initiative(ADNI) participants who were cognitively normal (CN; n=86) or had Mild Cognitive impairment (MCI; n=135) or AD (n=66). Statistical analyses were conducted using SPSS software. Multinomial regression analyses tested if higher ENPP2 was associated with higher relative risk ratios for MCI or AD diagnosis, relative to the CN reference group. Mixed model analyses were used to regress ENPP2 against metabolic, MRI, FDG‐PET and cognitive outcomes. Then on‐parametric Spearman's statistic was used to correlate ENPP2 and CSF biomarker values. T1‐weighted MRI images were preprocessed using FreeSurfer 4.3, and cortical thickness was examined in8 bilateral regions of interest. CSF ENPP2 levels strongly corresponded with CSF insulin‐like growth factor binding protein 2, an established biomarker of glucoregulatory function, and systemic fasting glucose. ENPP2 levels were higher in MCI and AD, and each point increase in log‐based ENPP2 values corresponded to a 3.5 to 5 times increase in the odds of having some degree of clinically relevant memory impairment. Higher ENPP2 predicted thinner PFC cortical thickness in most regions of interest in AD such as medialorbitofrontal cortex, and pars orbital is in MCI. In addition, less bilateral prefrontal cortex glucose metabolism was seen in AD. ENPP2 was also positively correlated with levels of total tau, p‐Tau181, total tau/Aβ1‐42, as well as pTau‐181/Aβ1‐42 to a marginal degree. This pattern suggests that CSF ENPP2 predicts AD neuropathology in a manner similar to dysmetabolism. Future studies should examine the potential benefit of decreasing ENPP2 levels in individuals with MCI or AD.Support or Funding InformationThis study was funded by Iowa State University and NIH K99 AG047282. Neither funding source had any involvement in the report. Data collection and sharing for this project were funded by the ADNI (National Institutes of Health Grant U01‐AG‐024904) and Department of Defense ADNI (award number W81XWH‐12‐2‐0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private‐sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. The data used in the preparation of this article were obtained from the ADNI database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report.

ERP C250 shows the elderly (cognitively normal, Alzheimer's disease) store more stimuli in short-term memory than Young Adults do.

To determine how aging and dementia affect the brain's initial storing of task-relevant and irrelevant information in short-term memory. We used brain Event-Related Potentials (ERPs) to measure short-term memory storage (ERP component C250) in 36 Young Adults, 36 Normal Elderly, and 36 early-stage AD subjects. Participants performed the Number-Letter task, a cognitive paradigm requiring memory storage of a first relevant stimulus to compare it with a second stimulus. In Young Adults, C250 was more positive for the first task-relevant stimulus compared to all other stimuli. C250 in Normal Elderly and AD subjects was roughly the same to relevant and irrelevant stimuli in Intratrial Parts 1-3 but not 4. The AD group had lower C250 to relevant stimuli in part 1. Both normal aging and dementia cause less differentiation of relevant from irrelevant information in initial storage. There was a large aging effect involving differences in the pattern of C250 responses of the Young Adult versus the Normal Elderly/AD groups. Also, a potential dementia effect was obtained. C250 is a candidate tool for measuring short-term memory performance on a biological level, as well as a potential marker for memory changes due to normal aging and dementia.

β-Amyloid Deposition Is Associated with Decreased Right Prefrontal Activation during Task Switching among Cognitively Normal Elderly.

The accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease, spatially overlaps with frontoparietal control (FPC) regions implicated in cognitive control, but the impact of Aβ deposition on FPC regions is largely unknown. Using functional magnetic resonance imaging with a task-switching task, we found Aβ-related increases in FPC regions compared with baseline activity. For higher cognitive control load, however, Aβ-related hypoactivity was found in the right inferior frontal cortex, a region highly implicated in cognitive control. The findings suggest that with Aβ deposition, task-related brain activity may reach a plateau early and undergo downstream pathways of neural dysfunction, which may relate to the early impairment of cognitive control seen in the progression of Aβ pathology.

Association between eating alone and depressive symptom in elders: a cross-sectional study.

BackgroundDepression is one of the main health concerns in elders which could lead to many negative outcomes. Eating alone is an emerging issue in elders in China and would become more serious along with the fast course of industrialization and urbanization, as well as population aging. However, their relationship was seldom researched.MethodsUsing a two-stage cluster sampling strategy, an investigation was conducted in 2014 among 9,361 permanent residents aged 60 years and above in Zhejiang Province, China. Totally, 7,968 cognitively normal elders were included in our analysis. Multilevel logistic regression was used to explore the association between eating arrangement (number of companions in mealtime) and depressive symptom as well as the association between eating alone and depressive symptom in relation to living alone.ResultsIn our sample, 17.1 % of the elders ate alone and 8.7 % had depressive symptom. We observed a distinct inverse association between eating arrangement (number of companions in mealtime) and geriatric depressive symptom (female: OR = 1.12, P = 0.027; aged 60–74 years: OR = 1.16, P = 0.002), after adjustment for demography, socioeconomic status, social relation, health behaviors, underlying conditions and living alone. We then introduced a combined variable of eating alone and living alone and examined its relationship with depressive symptom. We found that compared with elders who ate and lived with others, those who ate alone but lived with others had a significant increased odds of depressive symptom (female: OR = 1.62, P = 0.027; aged 60–74 years: OR = 1.59, P = 0.025).ConclusionsOur results suggested that a lack of companionship in mealtime might be independently associated with geriatric depressive symptom for females and those aged 60–74 years. What’s more, eating alone might be a stronger factor associated with depressive symptom than living alone. We recommend interventions to be performed in encouraging elders especially females and those aged 60–74 years to eat with others. Longitudinal studies in different populations which focus on this topic are required to better understand this issue.

Disproportionate Decline of Executive Functions in Early Mild Cognitive Impairment, Late Mild Cognitive Impairment, and Mild Alzheimer’s Disease

Background and PurposeMany literatures indicate that executive dysfunction exists in mild cognitive impairment (MCI) as well as Alzheimer’s disease (AD). However, there are few studies that found how early the deficits of the executive function (EF) exist in MCI. The present study investigated the presence of executive dysfunctions in the earliest stage of MCI, and the sub-domains of EF which are disproportionately impaired earlier than others.MethodsThe participants were 41 normal elderly (NE), 86 with amnestic multi-domain MCI, and 41 with mild AD. The MCI group was further sub-divided into two groups: Early MCI (EMCI, n=45) and late MCI (n=41), based on the Clinical Dementia Rating-Sum of Boxes. All participants were given neuropsychological tests to assess the sub-domains of EF, such as verbal fluency, psychomotor speed, inhibitory control, and mental set-shifting.ResultsImpairment of semantic fluency was observed in EMCI, with gradual worsening as cases approached mild AD. Phonemic fluency and psychomotor speed were also impaired at the early stage of MCI relative to the NE, but maintained at the same level up to mild AD. EMCI exhibited the same degree of performance with NE for inhibitory control and mental set-shifting; however, they progressively worsened from EMCI to mild AD.ConclusionsThese results suggest that impairments of EF exist even in the earliest stage of the MCI, with a disproportionate decline in the sub-domains of EF.

Construction and Validation of Brain MRI Templates from a Korean Normal Elderly Population.

ObjectiveThis study aimed to construct a Korean normal elderly brain template (KNE96) using Korean elderly individuals for use in brain MRI studies and to validate it.MethodsWe used high-resolution 3.0T T1 structural MR images from 96 Korean normal elderly individuals (M/F=48/48), aged 60 years or older (M=69.5±6.2 years, F=70.1±7.0 years), for constructing the KNE96 template. The KNE96 template was validated by comparing the registration-induced deformations between the KNE96 and ICBM152 templates using different MR images from 48 Korean normal elderly individuals (M/F=24/24), aged 60 years or older (M=71.5±5.9 years, F=72.8±5.1 years). We used the magnitude of displacement vectors (mag-displacement) and log of Jacobian determinants (log-Jacobian) to quantify the deformation produced during registration process to templates.ResultsThe mag-displacement and log-Jacobian of the registration were much smaller using the KNE96 template than with the ICBM152 template in most brain regions. There was a prominent difference in the significant averaged differences (SADs) of the mag-displacement and log-Jacobian between the KNE96 and ICBM152 at the superior, medial, and middle frontal gyrus, the lingual, inferior, middle, and superior occipital gyrus, and the caudate and thalamus.ConclusionThis study suggests that templates constructed from Asian populations, such as the KNE96, may be more desirable than those from Caucasian populations, like the ICBM152, in computational neuroimaging studies that measure and compare anatomical features of the frontal and occipital lobe, thalamus and caudate.

Relationship between eating disturbance and dementia severity in patients with Alzheimer's disease.

BackgroundEating is one of the most important daily activities in managing patients with dementia. Although various eating disturbance occur as dementia progresses, to our knowledge, most of the studies focused on a part of eating disturbance such as swallowing and appetite. There have been few comprehensive studies including eating habits and food preference in patients with Alzheimer’s disease (AD). The aims of this study were to investigate almost all eating disturbance and to examine the relationship of eating disturbance to dementia stage in AD.MethodsA total of 220 patients with AD and 30 normal elderly (NE) subjects were recruited. Eating disturbance was assessed by a comprehensive questionnaire that had been previously validated. Potential relationships between the characteristics of eating disturbance and dementia stage as classified by the Clinical Dementia Rating (CDR) were assessed.ResultsOverall, 81.4% of patients with AD showed some eating and swallowing disturbance, whereas only 26.7% of the NE subjects had such a disturbance. Even in an early stage, patients with AD had many types of eating disturbance; “Appetite change” was shown in nearly half of the mild AD patients (49.5%). In the moderate stage, the scores of “change of eating habits and food preference” were highest, and in the severe stage “swallowing disturbance” became critical.ConclusionIn AD, the relationship of dementia stage to eating disturbance differs according to the type of eating disturbance. The relationships between various eating disturbance and the severity of dementia should be considered.

Effects of Obesity on Functional Fitness and Anti-aging Hormones in Normal Weight and Overweight Elderly Women

Effects of Obesity on Functional Fitness and Anti-aging Hormones in Normal Weight and Overweight Elderly Women

Cognitive and Brain Profiles Associated with Current Neuroimaging Biomarkers of Preclinical Alzheimer's Disease.

Neuroimaging biomarkers, namely hippocampal volume loss, temporoparietal hypometabolism, and neocortical β-amyloid (Aβ) deposition, are included in the recent research criteria for preclinical Alzheimer's disease (AD). However, how to use these biomarkers is still being debated, especially regarding their sequence. Our aim was to characterize the cognitive and brain profiles of elders classified as positive or negative for each biomarker to further our understanding of their use in the preclinical diagnosis of AD. Fifty-four cognitively normal individuals (age = 65.8 ± 8.3 years) underwent neuropsychological tests (structural MRI, FDG-PET, and Florbetapir-PET) and were dichotomized into positive or negative independently for each neuroimaging biomarker. Demographic, neuropsychological, and neuroimaging data were compared between positive and negative subgroups. The MRI-positive subgroup had lower executive performances and mixed patterns of lower volume and metabolism in AD-characteristic regions and in the prefrontal cortex. The FDG-positive subgroup showed only hypometabolism, predominantly in AD-sensitive areas extending to the whole neocortex, compared with the FDG-negative subgroup. The amyloid-positive subgroup was older and included more APOE ε4 carriers compared with the amyloid-negative subgroup. When considering MRI and/or FDG biomarkers together (i.e., the neurodegeneration-positive), there was a trend for an inverse relationship with Aβ deposition such that those with neurodegeneration tended to show less Aβ deposition and the reverse was true as well. Our findings suggest that: (1) MRI and FDG biomarkers provide complementary rather than redundant information and (2) relatively young cognitively normal elders tend to have either neurodegeneration or Aβ deposition, but not both, suggesting additive rather than sequential/causative links between AD neuroimaging biomarkers at this age. Significance statement: Neuroimaging biomarkers are included in the recent research criteria for preclinical Alzheimer's disease (AD). However, how to use these biomarkers is still being debated, especially regarding their sequence. Our findings suggest that MRI and FDG-PET biomarkers should be used in combination, offering an additive contribution instead of reflecting the same process of neurodegeneration. Moreover, the present study also challenges the hierarchical use of the neuroimaging biomarkers in preclinical AD because it suggests that the neurodegeneration observed in this population is not due to β-amyloid deposition. Rather, our results suggest that β-amyloid- and tau-related pathological processes may interact but not necessarily appear in a systematic sequence.

APOE Effects on Default Mode Network in Chinese Cognitive Normal Elderly: Relationship with Clinical Cognitive Performance

BackgroundFunctional connectivity in default mode network (DMN) may be changed in Alzheimer’s disease (AD) patients and related risk populations, such as amnestic mild cognitive impairment (aMCI) patients and APOE ε4 carriers. Exploring DMN changes and related behavioral performance of APOE ε4 population might provide valuable evidence for better understanding the development of AD.MethodsSubjects were enrolled from a population-based cohort established in a multi-center study in China. Forty-nine cognitive normal individuals were enrolled after standardized cognitive evaluations, MRI examination and APOE genotyping. Regions of interest (ROI)-based functional connectivity analyses were performed, and voxel-based analyses were used to validate these findings. The correlation between DMN functional connectivity and behavioral performance was further evaluated between APOE ε4ε3 and ε3ε3 carriers.ResultsComparing to ε3ε3 carriers, functional connectivity between left parahippocampal gyrus and right superior frontal cortex (LPHC-R.Sup.F), left parahippocampal gyrus and medial prefrontal cortex (ventral) (LPHC-vMPFC) were significantly increased in ε4ε3 carriers, while connectivity between cerebellar tonsils and retrosplenial was decreased. LPHC-R.Sup.F connectivity was positively correlated with the changes of delay recall from baseline to follow-up (r = 0.768, p = 0.009), while LPHC-vMPFC connectivity had a positive correlation with MMSE at baseline (r = 0.356, p = 0.018), and a negative correlation with long-delayed recognition at follow-up (r = -0.677, p = 0.031). Significantly increased functional connectivity in vMPFC was confirmed in voxel-based analyses by taking LPHC as seed region.ConclusionAPOE ε4 carriers present both increased and decreased functional connectivity in DMN, which is correlated with clinical cognitive performances. DMN changes might be an early sign for cognitive decline.

Subtle visuomotor difficulties in preclinical Alzheimer's disease.

Individuals with preclinical Alzheimer's disease (Pre-AD) present nonimpaired cognition, as measured by standard neuropsychological tests. However, detecting subtle difficulties in cognitive functions may be necessary for an early diagnosis and intervention. A new computer-based visuomotor coordination task (VMC) was developed to investigate the possible presence of early visuomotor difficulties in Pre-AD individuals. Associations between VMC task performance and AD biomarkers were studied. The influence of ApoE status on participants' performance was addressed, as well as the relationship between performance and subjective cognitive decline (SCD). Sixty-six cognitively normal (CN) elders (19 Pre-AD and 47 control participants [CTR]) and 15 patients with AD performed the VMC task, which consisted in executing visually guided goal-directed movements that required the coordination of the visual and motor systems. All participants underwent ApoE analysis and lumbar puncture. CN participants also completed an extensive standard neuropsychological battery. Despite presenting normal cognition in standard tests, Pre-AD participants exhibited higher response times (RTs) to complete the VMC task than CTR (p<.01). Besides, patients with AD showed higher RTs than CTR (p<.001) and Pre-AD (p<.05), and more errors than CTR (p<.005). RTs in ApoE4 carriers were higher than that observed in ApoE4 noncarriers (p<.01). In CN individuals, RTs were related to amyloid β-protein 42 (AB42) biomarker (p<.01) and informant-rated SCD (p<.01). The VMC task is able to discriminate Pre-AD from CTR individuals. Moreover, VMC results are associated with AB42 levels in CN individuals, suggesting that visuomotor dysfunction may be a sensitive marker of Pre-AD.