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Limbic-predominant age-related TDP-43 encephalopathy (LATE) affects approximately one-third of older individuals and is associated with cognitive impairment. However, there is a highly incomplete understanding of the genetic determinants of LATE neuropathologic changes (LATE-NC) in diverse populations. The defining neuropathologic feature of LATE-NC is TDP-43 proteinopathy, often with comorbid hippocampal sclerosis (HS). In terms of genetic risk factors, LATE-NC and/or HS are associated with single nucleotide variants (SNVs) in 3 genes-TMEM106B (rs1990622), GRN (rs5848), and ABCC9 (rs1914361 and rs701478). We evaluated these 3 genes in convenience samples of individuals of African ancestry. The allele frequencies of the LATE-associated alleles were significantly different between persons of primarily African (versus European) ancestry: In persons of African ancestry, the risk-associated alleles for TMEM106B and ABCC9 were less frequent, whereas the risk allele in GRN was more frequent. We performed an exploratory analysis of data from African-American subjects processed by the Alzheimer's Disease Genomics Consortium, with a subset of African-American participants (n = 166) having corroborating neuropathologic data through the National Alzheimer's Coordinating Center (NACC). In this limited-size sample, the ABCC9/rs1914361 SNV was associated with HS pathology. More work is required concerning the genetic factors influencing non-Alzheimer disease pathology such as LATE-NC in diverse cohorts.

Psychosis is a common and distressing symptom in people with Alzheimer disease, and few safe and effective treatments are available. However, new approaches to symptom assessment and treatment are beginning to drive the field forward. New nosological perspectives have been provided by incorporating the emergence of psychotic symptoms in older adults - even in advance of dementia - into epidemiological and neurobiological frameworks as well as into diagnostic and research criteria such as the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders, the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) research criteria for psychosis in neurodegenerative disease, and the ISTAART criteria for mild behavioural impairment. Here, we highlight the latest findings in genomics, neuroimaging and neurobiology that are informing approaches to drug discovery and repurposing. Current pharmacological and non-pharmacological treatment options are discussed, with a focus on safety and precision medicine. We also explore trial data for pimavanserin, a novel agent that shows promise for the treatment of psychosis in people with dementia, and discuss existing agents that might be useful but need further exploration such as escitalopram, lithium, cholinesterase inhibitors and vitamin D. Although the assessment and management of psychosis in people with dementia remain challenging, new opportunities are providing direction and hope to the field.

Dementia-related behavioral and psychology symptoms (BPSD) are undertreated and have negative consequences. However, families do not have access to disease information, tailored problem-solving  and effective management strategies, and with COVID-19, are more socially isolated and distressed. To address this dementia care gap, we describe a Phase III efficacy trial testing an online platform, WeCareAdvisor, and design modifications necessitated by COVID-19. WeCareAdvisor provides caregivers with disease information, daily tips, and a systematic approach for describing behaviors, investigating underlying causes, creating tailored strategies, and evaluating their effectiveness (DICE). The trial will enroll 326 caregivers nationwide, randomly assign them to immediately receive WeCareAdvisor (treatment), or a 3-month waitlist (control) and evaluate short (1- and 3-month) and long-term (6-month) outcomes for caregiver distress with and confidence managing BPSD, and BPSD occurrences. We will also evaluate utilization patterns with different prompting conditions: high-intensity (telephone and email reminders), low-intensity (email reminders), or no reminders to use WeCareAdvisor. COVID-19 necessitated design modifications resulting in greater inclusivity of caregivers from diverse races, ethnicities, and geographic areas. Key modifications include shifting from in-home, in-person interviewing to telephone; adjusting tool functionality from operating on a grant-funded iPad to caregivers' personal internet-capable devices; and expanding recruitment from one metropolitan area to nationwide. Study modifications necessitated by COVID-19 facilitate national outreach, easier tool adoption, and enable more diverse caregivers to participate. This study addresses a critical dementia care need, and design modifications may shorten timeline from efficacy testing to commercialization.

Deep brain stimulation has been investigated as a potential treatment for cognitive impairments in Alzheimer’s disease. Here the authors carry out post hoc analysis of multi-center cohorts to investigate the anatomical and functional correlates of effective deep brain stimulation, and find that stimulating circuit of Papez, fornix and bed nucleus of the stria terminalis, and a multi-region functional network, were associated with clinical improvement.

Introduction: Alzheimer’s disease (AD) is currently defined according to biomarkers reflecting the core underlying neuropathological processes: Aβ deposition, Tau, and neurodegeneration (ATN). The soluble phase of plasma and plasma neuron-derived extracellular vesicles (NDEVs) are increasingly being investigated as sources of biomarkers. The aim of this study was to examine the comparative biomarker potential of these two biofluids, as well as the association between respective biomarkers.Methods: We retrospectively identified three distinct diagnostic groups of 44 individuals who provided samples at baseline and at a mean of 3.1 years later; 14 were cognitively unimpaired at baseline and remained so (NRM-NRM), 13 had amnestic MCI that progressed to AD dementia (MCI-DEM) and 17 had AD dementia at both timepoints (DEM-DEM). Plasma NDEVs were isolated by immunoaffinity capture targeting the neuronal markers L1CAM, GAP43, and NLGN3. In both plasma and NDEVs, we assessed ATN biomarkers (Aβ42, Aβ40, total Tau, P181-Tau) alongside several other exploratory markers.Results: The Aβ42/Aβ40 ratio in plasma and NDEVs was lower in MCI-DEM than NRM-NRM at baseline and its levels in NDEVs decreased over time in all three groups. Similarly, plasma and NDEV-associated Aβ42 was lower in MCI-DEM compared to NRM-NRM at baseline and its levels in plasma decreased over time in DEM-DEM. For NDEV-associated proBDNF, compared to NRM-NRM, its levels were lower in MCI-DEM and DEM-DEM at baseline, and they decreased over time in the latter group. No group differences were found for other exploratory markers. NDEV-associated Aβ42/Aβ40 ratio and proBDNF achieved the highest areas under the curve (AUCs) for discriminating between diagnostic groups, while proBDNF was positively associated with Mini-Mental State Examination (MMSE) score. No associations were found between the two biofluids for any assessed marker.Discussion: The soluble phase of plasma and plasma NDEVs demonstrate distinct biomarker profiles both at a single time point and longitudinally. The lack of association between plasma and NDEV measures indicates that the two types of biofluids demonstrate distinct biomarker signatures that may be attributable to being derived through different biological processes. NDEV-associated proBDNF may be a useful biomarker for AD diagnosis and monitoring.

Objectives: We investigated the association between neuropsychiatric symptoms (NPS) and frontotemporal atrophy (FTA) in older adults without dementia. We hypothesized that the odds of having NPS would be increased in the presence of FTA. Methods: NACC participants ≥ 50 years old with available data on FTA were considered for eligibility. Those with a diagnosis of mild cognitive impairment (MCI) and those who were cognitively unimpaired (CU) were separately analyzed. NPS were quantified on the Neuropsychiatric Inventory Questionnaire. Binary logistic regression models estimated the association (odds ratios and 95% confidence intervals are provided) between FTA and having each of 11 NPS (psychotic symptoms were grouped together) in CU and MCI individuals. Results: FTA data were available for 3165 participants with MCI and 4051 CU: 207 and 55 had FTA on structural MRI studies, respectively. In the MCI group, the presence of FTA was associated with higher odds of having elation [2.42(1.33–4.40), p = 0.004], aberrant motor behavior [2.43(1.61–3.69), p < 0.001], appetite disorders [2.15(1.52–3.04), p < 0.001], apathy [2.05(1.48–2.85), p < 0.001] and disinhibition [2.02(1.38–2.96), p < 0.001]. The odds of having specific NPS were not significantly elevated in CU individuals with FTA. Of note, the size and direction of the associations were indicative of a potential relationship between FTA and specific NPS (most notably elation, aberrant motor behavior, appetite disorders and anxiety); in light of the small number of CU individuals with FTA we believe this analysis was underpowered and obscured several true associations. Conclusions: FTA was associated with higher odds of some NPS in older adults with MCI but not with normal cognition. [ABSTRACT FROM AUTHOR]

Agitation is one of the most eminent characteristics of neuropsychiatric symptoms (NPS) affecting people living with Alzheimer’s and Dementia and has serious consequences for patients and caregivers. The current consensus is that agitation results, in part, from the disruption of ascending monoamine regulators of cortical circuits, especially the loss of serotonergic activity. It is believed that the first line of treatment for these conditions is selective serotonin reuptake inhibitors (SSRIs), but these are effective in only about 40% of patients. Person-specific biomarkers, for example, ones based on in vitro iPSC-derived models of serotonin activity, which predict who with Agitation responds to an SSRI, are a major clinical priority. Here, we report the generation of human-induced pluripotent stem cells (iPSCs) from a 74-year-old AD patient, the homozygous APOE ε4/ε4 carrier, who developed Agitation. His iPSCs were reprogrammed from peripheral blood mononuclear cells (PBMCs) using the transient expression of pluripotency genes. These display typical iPSC characteristics that are karyotypically normal and attain the capacity to differentiate into three germ layers. The newly patient-derived iPSC line offers a unique resource to investigate the underlying mechanisms associated with neuropsychiatric symptom progression in AD.

Objective: Cholinesterase inhibitors (CEIs) are prescribed for dementia to maintain or improve memory. Selective serotonin reuptake inhibitors (SSRIs) are also prescribed to manage psychiatric symptoms seen in dementia. What proportion of outpatients actually responds to these drugs is still unclear. Our objective was to investigate the responder rates of these medications in an outpatient setting using the electronic medical record (EMR).Methods: We used the Johns Hopkins EMR system to identify patients with dementia who were prescribed a CEI or SSRI for the first time between 2010 and 2021. Treatment effects were assessed through routinely documented clinical notes and free-text entries in which healthcare providers record clinical findings and impressions of patients. Responses were scored using a three-point Likert scale named the NOte-based evaluation method for Treatment Efficacy (NOTE) in addition to the Clinician’s Interview-Based Impression of Change Plus caregiver input (CIBIC-plus), a seven-point Likert scale used in clinical trials. To validate NOTE, the relationships between NOTE and CIBIC-plus and between NOTE and change in MMSE (Mini-Mental State Examination) before and after medication were examined. Inter-rater reliability was evaluated using Krippendorff’s alpha. The responder rates were calculated.Results: NOTE showed excellent inter-rater reliability and correlated well with CIBIC-plus and changes in MMSEs. Out of 115 CEI cases, 27.0% reported improvement and 34.8% reported stable symptoms in cognition; out of 225 SSRI cases, 69.3% reported an improvement in neuropsychiatric symptoms.Conclusion: NOTE showed high validity in measuring the pharmacotherapy effects based on unstructured clinical entries. Although our real-world observation included various types of dementia, the results were remarkably similar to what was reported in controlled clinical trials of Alzheimer’s disease and its related neuropsychiatric symptoms.

BACKGROUND:Behavioral and psychological symptoms of dementia (BPSD) are universal and associated with multiple negative outcomes. This pilot randomized controlled trial (RCT) evaluated the effect of using the WeCareAdvisor, an innovative web-based tool developed to enable family caregivers to assess, manage, and track BPSD. METHODS:This RCT enrolled 57 dementia family caregivers from community and clinical settings in Ann Arbor, Michigan and Baltimore, Maryland. Participants were randomly assigned to immediate use of the WeCareAdvisor tool (WCA, n = 27) or a Waitlist control group (n = 30) that received the tool after a one-month waiting period. Outcomes for the caregiver and the person they were caring for were assessed at baseline (T0) and one-month followup for both the WCA (T1) and Waitlist control (T2) groups. RESULTS:Caregiver mean age was 65.9 ± 14.0 years old. About half (49%) were spouses. Baseline characteristics were comparable between groups except for mean caregiver confidence which was higher in the control group (WCA 35.0 ± 10.0 vs. Waitlist control 39.7 ± 6.9, p = 0.04). There were no significant differences between the WCA and control groups in characteristics of the person with dementia. After their one-month of tool use (T1), WCA caregivers showed significant within group improvement in caregiver distress (- 6.08 ± 6.31 points, t = - 4.82, p

Abstract Objectives As epidemiological studies become longer and larger, the field needs novel graphical methods to visualize complex longitudinal data. The aim of this study was to present the Slinkyplot, a longitudinal crosstabulation, to illustrate patterns of antidepressant use in a large prospective cohort of older adults with mild cognitive impairment. Methods Data from the National Alzheimer's Coordinating Center are used to track switches between different states and types of antidepressant use. A Slinkyplot is populated with rows representing the state of medication use at each timepoint and columns representing the state at each subsequent visit. Results The constructed Slinkyplots display the common practice of switching on and off different antidepressants over time, with citalopram, sertraline, and bupropion most commonly used followed by switching to another SSRI or SNRI as second‐line treatment. Conclusions Slinkyplots are an innovative graphical means of visualizing complex patterns of transitions between different states over time for large longitudinal studies.

IntroductionA national consensus panel was convened to develop recommendations on future directions for home-based dementia care (HBDC).MethodsThe panel summarized advantages and challenges of shifting to HBDC as the nexus of care and developed consensus-based recommendations.ResultsThe panel developed five core recommendations: (1) HBDC should be considered the nexus of new dementia models, from diagnosis to end of life in dementia; (2) new payment models are needed to support HBDC and reward integration of care; (3) a diverse new workforce that spans the care continuum should be prepared urgently; (4) new technologies to promote communication, monitoring/safety, and symptoms management must be tested, integrated, and deployed; and (5) targeted dissemination efforts for HBDC must be employed.DiscussionHBDC represents a promising paradigm shift to improve care for those living with dementia and their family caregivers: these recommendations provide a framework to chart a course forward for HBDC.

Background/objectivesBehavioral and psychological symptoms of dementia (BPSD) are nearly universal in dementia and associated with multiple negative outcomes. Current real-world management is largely pharmacologic, despite poor risk/benefit. The WeCareAdvisor was designed to enable family caregivers to assess, manage, and track BPSD using nonpharmacologic strategies.DesignIn-depth qualitative data were collected from family caregivers of people with dementia to inform: (1) style of approach and "look and feel" of the tool, and (2) the types of psychoeducation most needed by caregivers.ResultsWe conducted 4 focus groups and a technology survey (n=26) as well as additional individual semistructured interviews (n=12) with family caregivers. Main themes of the qualitative work included: (1) need to minimize difficulty and training time; (2) importance of "one-stop shopping" for information; and (3) necessity for information to be tailored to the caregiver and person with dementia. This information was then combined with effective existing evidence-based behavioral strategies to create a web-based tailored caregiver-support tool.ConclusionsThe WeCareAdvisor was designed with input on functionality and content by end-users, family caregivers. The randomized controlled trial of WeCareAdvisor will test whether the tool improves outcomes including caregiver upset and burden and frequency and severity of BPSD.

A significant number of breast cancer survivors are living with their minor children. In this review we investigated the impact of maternal breast cancer on children. A literature search conducted through PubMed, Scopus, Cochrane Library and CINAHL yielded 26 relevant studies, which documented a variety of effects. Evidence has been presented that dealing with maternal breast cancer can cause uncertainty, anxiety and depression in children, but may also lead to enhanced social and academic performance. The risk of problems in these children is reported to be associated with both low parental affective responsiveness and excessive parental involvement. Internalising child problems were shown to be linked with maternal depression and family dysfunction, and externalising problems with family dysfunction and communication problems. Some of these problems may be modified by interventions for supporting these families, which should be designed to include both parents and children, and also the healthcare personnel.

The recent advances in creating pluripotent stem cells from somatic cells and differentiating them into a variety of cell types is allowing us to study them without the caveats associated with disease-related changes. We generated induced Pluripotent Stem Cells (iPSCs) from eight Alzheimer’s disease (AD) patients and six controls and used lentiviral delivery to differentiate them into excitatory glutamatergic neurons. We then performed RNA sequencing on these neurons and compared the Alzheimer’s and control transcriptomes. We found that 621 genes show differences in expression levels at adjusted p < 0.05 between the case and control derived neurons. These genes show significant overlap and directional concordance with genes reported from a single-cell transcriptome study of AD patients; they include five genes implicated in AD from genome-wide association studies and they appear to be part of a larger functional network as indicated by an excess of interactions between them observed in the protein–protein interaction database STRING. Exploratory analysis with Uniform Manifold Approximation and Projection (UMAP) suggests distinct clusters of patients, based on gene expression, who may be clinically different. Our research outcomes will enable the precise identification of distinct biological subtypes among individuals with Alzheimer’s disease, facilitating the implementation of tailored precision medicine strategies.

Objective: We aimed to examine associations between neuropsychiatric symptoms (NPS) and white matter hyperintensities (WMH) status in older adults without dementia under the hypothesis that WMH increased the odds of having NPS. Design: Longitudinal analysis of data acquired from the National Alzheimer's Coordinating Center Uniform Data Set. Settings: Data were derived from 46 National Institute on Aging – funded Alzheimer's Disease Research Centers. Participants: NACC participants aged ≥50 years with available data on WMH severity with a diagnosis of mild cognitive impairment (MCI) or who were cognitively unimpaired (CU) were studied. Among 4617 CU participants, 376 had moderate and 54 extensive WMH. Among 3170 participants with MCI, 471 had moderate and 88 had extensive WMH. Measurements: Using Cardiovascular Health Study (CHS) scores, WMH were coded as no to mild (CHS score: 0–4), moderate (score: 5–6) or extensive (score: 7–8). NPS were quantified on the Neuropsychiatric Inventory Questionnaire. Binary logistic regression models estimated the odds of reporting each of 12 NPS by WMH status separately for individuals with MCI or who were CU. Results: Compared to CU individuals with no to mild WMH, the odds of having elation [9.87, (2.63–37.10)], disinhibition [4.42, (1.28–15.32)], agitation [3.51, (1.29–9.54)] or anxiety [2.74, (1.28–5.88)] were higher for the extensive WMH group, whereas the odds of having disinhibition were higher for the moderate WMH group [1.94, (1.05–3.61)]. In the MCI group, he odds of NPS did not vary by WMH status. Conclusions: Extensive WMH were associated with higher odds of NPS in CU older adults but not in those with MCI. [ABSTRACT FROM AUTHOR]

Abstract Introduction Traumatic brain injury (TBI) may alter dementia progression, although co‐occurring neuropsychiatric symptoms (NPS) have received less attention. Originally designed to evaluate behavioral disruption prior to dementia diagnosis, the mild behavioral impairment (MBI) construct relates NPS to underlying neural circuit disruptions, with probable relevance across the progression of neurodegenerative disease. Therefore, the MBI construct may represent a valuable tool to identify and evaluate related NPS both preceding diagnosis of all‐cause dementia throughout the progression of disease, representing an important area of inquiry regarding TBI and dementia. This investigation sought to evaluate the effect of TBI on NPS related by the MBI construct in participants progressing from normal cognitive status to all‐cause dementia. Methods Using National Alzheimer's Coordinating Center data, individuals progressing from normal cognition to all‐cause dementia (clinician diagnosed) over 7.6 ± 3.0 years were studied to estimate prevalence of MBI domains in 124 participants with prior TBI history (57 with loss of consciousness [LOC] 5 min, 45 unknown severity) compared to 822 without. MBI domain prevalence was evaluated (1) prior to dementia onset (including only time points preceding time at dementia diagnosis, as per MBI's original definition) and (2) throughout dementia progression (evaluating all available time points, including both before and after dementia diagnosis). Results More severe TBI (LOC >5 minutes) was associated with the social inappropriateness MBI domain (adjusted odds ratio = 4.034; P = 0.024) prior to dementia onset, and the abnormal perception/thought content domain looking across dementia progression (adjusted hazard ratio [HRadj] = 3.703; P = 0.005). TBI (all severities) was associated with the decreased motivation domain looking throughout dementia progression (HRadj. = 1.546; P = 0.014). Discussion TBI history is associated with particular MBI profiles prior to onset and throughout progression of dementia. Understanding TBI's impact on inter‐related NPS may help elucidate underlying neuropathology with implications for surveillance, detection, and treatment of behavioral concerns in aging TBI survivors. Highlights The mild behavioral impairment (MBI) construct links related neuropsychiatric symptoms (NPS) by probable underlying neural network dysfunction. Traumatic brain injury (TBI) with loss of consciousness (LOC) > 5 minutes was associated with pre‐dementia social inappropriateness. TBI was associated with decreased motivation looking across dementia progression. TBI with LOC > 5 minutes was associated with abnormal perception/thought content. The MBI construct may be useful for examining related NPS across dementia progression.

IntroductionPlasma levels of amyloid-beta (Aβ) do not correlate well with different stages of Alzheimer's disease (AD) in cross-sectional studies. Measuring the changes in Aβ plasma levels with an acute intervention may be more sensitive to distinguishing individuals in earlier stages of AD (mild cognitive impairment; MCI) from normal controls.Methods57 participants (18 with AD/MCI and 39 cognitively normal controls) underwent oral glucose tolerance testing (OGTT). Blood samples were obtained over a 2 hour time period. Changes in plasma Aβ40 and42 levels were measured from either baseline or 5 minutes to the 10 minute time point.ResultsCompared to normal controls, subjects with AD/MCI had significantly less change (Δ) in plasma levels for both Aβ40(-3.13(40.93)pg/ml vs. 41.34(57.16)pg/ml;p=0.002) and Aβ42(-0.15(3.77)pg/ml vs. 5.64(10.65)pg/ml; p=0.004).DiscussionOGTT combined with measures of plasma Aβ40 and 42 is potentially useful in distinguishing aging individuals who are in different stages of AD.

Noncognitive neuropsychiatric symptoms (NPS) of dementia (aggression, agitation, depression, anxiety, delusions, hallucinations, apathy, disinhibition) affect individuals with dementia nearly universally across dementia stages and etiologies. NPS are associated with poor outcomes for individuals with dementia and caregivers, including excess morbidity and mortality, greater healthcare use, and earlier nursing home placement, as well as caregiver stress, depression, and difficulty with employment. Although the Food and Drug Administration has not approved pharmacotherapy for NPS, psychotropic medications are frequently used to manage these symptoms, but in the few cases of proven pharmacological efficacy, significant risk of adverse effects may offset benefits. There is evidence of efficacy and limited potential for adverse effects of nonpharmacological treatments, typically considered first line, but their uptake as preferred treatments remains inadequate in real-world clinical settings. Thus, the field currently finds itself in a predicament in terms of management of these difficult symptoms. It was in this context that the University of Michigan Program for Positive Aging, working in collaboration with the Johns Hopkins Alzheimer's Disease Research Center and Center for Innovative Care in Aging sponsored and convened a multidisciplinary expert panel in Detroit, Michigan, in fall 2011 with three objectives: to define critical elements of care for NPS in dementia; to construct an approach describing the sequential and iterative steps of managing NPS in real-world clinical settings that can be used as a basis for integrating nonpharmacological and pharmacological approaches; and to discuss how the approach generated could be implemented in research and clinical care.

The paper is dedicated to investigations of tribological characteristics of experimental tool hard alloy (HA) grades based on tungsten carbide with modified cobalt binder under conditions of dry friction on disks made of titanium-aluminum alloy VT-3, as well as measures of their surface micro-hardness. All measured parameters were compared with similar characteristics of standard HA grade VK8, on the basis of which these experimental grades were developed. The research found that the surface micro-hardness of all experimental HA grades as pins were higher than that for the basic grade VK8; the highest value was fixed for the HA grade with symbol mark 2.22 (composition of the binder - 5.65% Co +1.8% Mo +0.6% Ti). The highest wear resistance was obtained for 2.23 (5.1%Co+2.7%Mo+0.61%Ti) and 2.21 (5.4%Co+1.43%Fe+0.82% Cu), the lowest – for grade 2.22. The analysis of friction processes peculiarities allows to explain the high wear resistance of grades 2.21 and 2.23 by features of surface structures ("the third body") formation during friction. Friction process for these HA grades include the periods of "the third body" intensive growth to the considerable thickness values, as well as the periods of its abrasion; due to this phenomena resulting wear rates for these two grades proved to be significantly lower than for the base grade VK8. The "third body" generated during friction protects surfaces from wear, at the same time it has its own significant shear resistance and increases actual contact area, due to this phenomena the friction forces for grades 2.21 and 2.23 are somewhat higher than for basic grade VK8. The grade 2.22 is characterized by the highest average friction force and its r.m.s. deviation value, which result in the greatest wear rates for both the HA pins and rotating disks. So according to the results of testing the best results among the investigated experimental HA grades were obtained for grade 2.23: the lowest average friction coefficient and the lowest track surface roughness on rotating disks, as well as the highest wear resistance values.

Aiming to examine whether specific motor signs are associated with worse performance in specific cognitive domains among cognitively unimpaired (CU) individuals, we performed a cross-sectional analysis of data from the baseline evaluations of older, CU participants from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set. In total, 8149 CU (≥60 years) participants were included. Of these, 905 individuals scored ≥ 2 on at least one of the motor domains of the Unified Parkinson’s Disease Rating Scale part III (UPDRSIII). Cognitively impaired individuals, participants with psychiatric disorders and/or under treatment with antipsychotic, anxiolytic, sedative or hypnotic agents were excluded. Nine motor signs were examined: hypophonia, masked facies, resting tremor, action/postural tremor, rigidity, bradykinesia, impaired chair rise, impaired posture/gait and postural instability. Their association with performance on episodic memory, semantic memory, language, attention, processing speed or executive function was assessed using crude and adjusted linear regression models. Individuals with impaired chair rise had worse episodic memory, semantic memory, processing speed and executive function, while those with bradykinesia had worse language, processing speed and executive function. Sensitivity analyses, by excluding participants with cerebrovascular disease or PD, or other Parkinsonism, produced similar results with the exception of the relationship between bradykinesia and language performance.