Kok Pin Ng

• Consultant at National Neuroscience Institute

Background18F-THK5351 is a quinoline-derived tau imaging agent with high affinity to paired helical filaments (PHF). However, high levels of 18F-THK5351 retention in brain regions thought to contain negligible concentrations of PHF raise questions about the interpretation of the positron emission tomography (PET) signals, particularly given previou...

Objective: To identify regional brain metabolic dysfunctions associated with neuropsychiatric symptoms (NPS) in preclinical Alzheimer disease (AD). Methods: We stratified 115 cognitively normal individuals into preclinical AD (both amyloid and tau pathologies present), asymptomatic at risk for AD (either amyloid or tau pathology present), or hea...

Background Neuropsychiatric symptoms (NPS) are increasingly recognized as early non-cognitive manifestations in the Alzheimer’s disease (AD) continuum. However, the role of NPS as an early marker of pathophysiological progression in AD remains unclear. Dominantly inherited AD (DIAD) mutation carriers are young individuals who are destined to develo...

Background: [18F]THK5351 is a tau positron emission tomography tracer that has shown promise in quantifying tau distribution in tauopathies such as Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). However, the interpretation of [18F]THK5351 uptake has been shown to be confounded by high monoamine oxidase B (MAO-B) availability ac...

Introduction: Cognitive assessment tools measure cognitive impairment and complement biomarkers to link cognitive symptoms with pathophysiological processes underlying dementia. However, language and cultural differences in multilingual populations can influence the interpretation of cognitive assessment tools when applied in cross-cultural and mul...

Cognition is one of the most widely used measure of brain health. Poor cognitive function reflects both the progression of neurodegenerative disorders and the decline of cardiometabolic conditions. Moreover, the genetic determinants of cognitive function are pleiotropic with various aspects of physical health and mortality. To date, little research...

Background Recent advancements in plasma pTau217 have shown its potential as a reliable biomarker for detecting brain amyloid pathology (Aβ) in Alzheimer’s disease (AD). However, its application in real-world settings remains limited, particularly in diverse populations such as those in Asia. While plasma pTau217 has demonstrated high accuracy in r...

Objective Subsyndromal symptomatic depression (SSD) is associated with an increased risk of cognitive impairment in non-demented older adults. However, the mechanism underlying this relationship remains unclear. This study aimed to investigate whether plasma neurofilament light chain (NfL) mediates the relationship between SSD and cognitive decline...

Background DNA methylation is an epigenetic change characterized by the addition of methyl groups to DNA, typically in the cytosine‐ phosphate‐guanine (CpG) nucleotide base pairings. Given that DNA methylation alterations are shown to be associated with Alzheimer’s Disease (AD) pathology in autopsied brains, blood‐based DNA methylation changes are...

Background Cognitive assessments are essential for the diagnosis of mild cognitive impairment (MCI) and dementia. However, existing tests are mostly developed in English‐speaking cohorts. Hence, their application in multilingual populations will need translation which may affect their test psychometrics. VCAT is a language‐neutral visual‐based asse...

Background Epilepsy is associated with increased risk for dementia, which adversely impacts the quality of life for patients and their families. Mild cognitive impairment (MCI) is the prodromal stage of dementia offering an important window for intervention. However, the epilepsy related risk factors for MCI are not well understood. The ongoing Mil...

The progression of PET-based Braak stages correlates with cognitive deterioration in aging and Alzheimer’s disease. Here, we investigate the association between PET-based Braak stages and functional impairment and assess whether PET-based Braak staging predicts a longitudinal decline in the performance of activities of daily living. In this cohort...

Background: Cognitive assessments for patients with neurocognitive disorders are mostly measured by the Montreal Cognitive Assessment (MoCA) and Visual Cognitive Assessment Test (VCAT) as screening tools. These cognitive scores are usually left-skewed and the results of the association analysis might not be robust. This study aims to study the dist...

Objectives Early detection of cognitive impairment is essential for timely intervention. Currently, most widely used cognitive screening tests are influenced by language and cultural differences; therefore, there is a need for the development of a language‐neutral, visual‐based cognitive assessment tool. The Visual Cognitive Assessment Test (VCAT),...

Background Mild behavioral impairment (MBI) is one of the earliest observable changes when a person experiences cognitive decline and could be an early manifestation of underlying Alzheimer’s disease neuropathology. Limited attention has been given to investigating the clinical applicability of behavioral biomarkers for detection of prodromal demen...

Background Continuous assessment and remote monitoring of cognitive function in individuals with mild cognitive impairment (MCI) enables tracking therapeutic effects and modifying treatment to achieve better clinical outcomes. While standardized neuropsychological tests are inconvenient for this purpose, wearable sensor technology collecting physio...

Background Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer’s disease that offers a window for early intervention prior to dementia onset. The cognitive impairment observed in MCI includes declines across several cognitive domains, including memory, processing speed, and executive function. Emerging evidence supports a multidomain...

Background Neuropsychiatric symptoms (NPS) are increasingly recognized as early non‐cognitive manifestations of patients at‐risk of dementia and are associated with accelerated cognitive decline. While cognitive stimulation may be an effective intervention in improving NPS and quality of life of patients and their caregivers, there is a need for a...

Background Behavioral and psychological symptoms are one of the earliest observable changes when a person experiences cognitive decline. These symptoms are common and are known as Neuropsychiatric symptoms(NPS), which increases risk of progression to dementia. The prevalence of NPS was compared in a cohort of Southeast Asian adults with Subjective...

Background Cognitive tests play a crucial role in evaluating mild cognitive impairment (MCI) and dementia. As most tests are originally developed in English‐speaking cohorts, their application in multilingual populations will need to be translated and may affect the test psychometrics. Therefore, the VCAT was developed as a language‐neutral visual‐...

Background Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer’s disease that offers a window for early intervention prior to dementia onset. The cognitive impairment observed in MCI includes declines across several cognitive domains, including memory, processing speed, and executive function. Emerging evidence supports a multidomain...

Background Neuropsychiatric symptoms (NPS) are increasingly recognized as early non‐cognitive manifestations of patients at‐risk of dementia and are associated with accelerated cognitive decline. While cognitive stimulation may be an effective intervention in improving NPS and quality of life of patients and their caregivers, there is a need for a...

Background: Cognitive for patients with neurocognitive disorders are mostly measured by Montreal Cognitive Assessment (MoCA) and Visual Cognitive Assessment Test (VCAT) as screening tools. These cognitive scores are usually left skewed and the results of association analysis might not be robust. This study aims to study the distribution of the cogn...

Background Post Stroke Cognitive Impairment (PSCI) is seen in 40‐60% of patients with ischemic strokes. Response of patients with PSCI to structured cognitive rehabilitation is not clearly understood. We evaluated baseline variables that predict response to an eight‐week non‐pharmacological intervention among patients with mild strokes and compared...

Background White matter hyperintensities (WMH) are a known risk factor for cognitive decline (C.Puzo el. al. 2019). While the ε4 allele of apolipoprotein E gene (APOE4) is another risk factor for cognitive decline in concomitance with WMH (D.Tsuang et. al. 2013), it remains unclear how APOE4 affects the relationship between WMH and cognitive declin...

Background Oligomeric Amyloid Beta (OAβ), is representative of a soluble, neurotoxic and pathogenic form of Aβ, which has been found to function as upstream drivers of Alzheimer’s Disease pathology (Tolar et al., 2021). It serves as a contributory factor towards the formation of cortical Aβ plaques and neurofibrillary Tau tangles, and has been foun...

Amyloid-β plaques and neurofibrillary tangles (NFTs) are the 2 histopathologic hallmarks of Alzheimer disease (AD). On the basis of the pattern of NFT distribution in the brain, Braak and Braak proposed a histopathologic staging system for AD. Braak staging provides a compelling framework for staging and monitoring of NFT progression in vivo using...

Background: White matter hyperintensities, a neuroimaging marker of small-vessel cerebrovascular disease and apolipoprotein ε4 (APOE4) allele, are important dementia risk factors. However, APOE4 as a key effect modifier in the relationship between white matter hyperintensities and grey matter volume needs further exploration. Methods: One hundre...

[This corrects the article DOI: 10.3389/fneur.2022.1005406.].

Objective: Frontotemporal dementia (FTD) encompasses a spectrum of neurodegenerative disorders, including behavioural variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA) and non-fluent variant PPA (nfvPPA). While a strong genetic component is implicated in FTD, genetic FTD in Asia is less frequently reported. We aimed to inve...

Mild behavioral impairment (MBI) describes the emergence of neurobehavioral symptoms in later life as harbingers of neurodegeneration. Emerging evidence suggests that white matter hyperintensity (WMH), a known risk factor for cognitive impairment, is associated with MBI. Furthermore, education level which reflects cognitive reserve, influences the...

With increasing research into novel disease modifying therapies for mild cognitive impairment (MCI) and mild dementia, there is a need for large scale early detection of cognitive disorders. However, existing cognitive evaluation tools largely cater for native English speakers. We designed and validated a novel visual based cognitive evaluation too...

Oligomeric amyloid‐beta (OAβ) is postulated to be the major neurotoxic species that is implicated in the pathophysiology of Alzheimer’s disease (AD). Emerging evidence suggest that plasma OAβ levels are higher in AD compared to cognitively unimpaired individuals and correlate well with AD biomarkers. Diabetes Mellitus (DM) is consistently linked to...

The APOE‐ε4 (APOE4) allele and cerebrovascular disease (CVD), represented by surrogate MRI measures involving white matter hyperintensities (WMH) are key dementia risk factors [Tosto et al.,2015; Mahley et al.,2006]. They relate to grey matter volume (GMV) and cognitive decline, and demonstrate increased occurrence with lowered age of dementia onse...

Aim This study aims to assess the integrity of white matter in various segments of the corpus callosum in Alzheimer's disease (AD) by using metrics derived from diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI) and white matter tract integrity model (WMTI) and compare these findings to healthy controls (HC). Methods The study was ap...

We examined amyloid-tau-neurodegeneration biomarker effects on cognition in a Southeast-Asian cohort of 84 sporadic young-onset dementia (YOD; age-at-onset <65 years) patients. They were stratified into A+N+, A– N+, and A– N– profiles via cerebrospinal fluid amyloid-β1–42 (A), phosphorylated-tau (T), MRI medial temporal atrophy (neurodegeneration–...

Background Large-scale neuronal network breakdown underlies memory impairment in Alzheimer’s disease (AD). However, the differential trajectories of the relationships between network organisation and memory across pathology and cognitive stages in AD remain elusive. We determined whether and how the influences of individual-level structural and met...

The burden imposed by the COVID-19 pandemic deferentially interferes with the outcomes of clinical trials of aging and dementia. We examined the impact of the lockdown on cognitive impairment due to Alzheimer’s Disease (AD), anxiety, and COVID-19-related stress in participants from the Translational Biomarkers In Aging and Dementia (TRIAD) cohort u...

Alzheimer’s disease (AD) is characterized by the brain accumulation of amyloid-β and tau proteins. A growing body of literature suggests that epigenetic dysregulations play a role in the interplay of hallmark proteinopathies with neurodegeneration and cognitive impairment. Here, we aim to characterize an epigenetic dysregulation associated with the...

The definitive diagnosis of Alzheimer's Disease (AD) without the need for neuropathological confirmation remains a challenge in AD research today, despite efforts to uncover the molecular and biological underpinnings of the disease process. Furthermore, the potential for therapeutic intervention is limited upon the onset of symptoms, providing moti...

Oligomeric amyloid-β (OAβ), an upstream driver of Alzheimer’s disease (AD) neuropathology, correlates with poor cognitive performance and brain volume reduction. Its effect on cognitive performance measured by the language neutral Visual Cognitive Assessment Test (VCAT) remains to be evaluated. We studied the correlation of plasma OAβ with VCAT sco...

Non paraneoplastic Lambert Eaton myasthenic syndrome (LEMS) is rare and only very few cases have been reported to date. Besides that, LEMS is rarely associated with cerebellar ataxia. Here, we described a case of middle age gentleman who presented with subacute onset of cerebellar ataxia and subsequently found to have remarkably elevated voltage-ga...

Background There is an urgent need for noninvasive, cost-effective biomarkers for Alzheimer’s disease (AD), such as blood-based biomarkers. They will not only support the clinical diagnosis of dementia but also allow for timely pharmacological and nonpharmacological interventions and evaluations. Objective To identify and validate a novel blood-ba...

Background White matter hyperintensities (WMH) are a known risk factor for cognitive decline. While the ɛ4 allele of apolipoprotein E gene (APOE4) is another risk factor for cognitive decline, it remains unclear how APOE4 affects the relationship between WMH and cognitive decline, specifically in the prodromal stage of dementia. Objective To deter...

Background Young-onset cognitive disorders (YOCD) often manifests with complex and atypical presentations due to underlying heterogenous pathologies. Therefore, a biomarker-based evaluation will allow for timely diagnosis and definitive management. Objective Here, we evaluated the safety and usefulness of cerebrospinal fluid (CSF) sampling through...

Background Large-scale neuronal network breakdown underlies memory impairment in Alzheimer’s disease (AD). However, the differential trajectories of the relationships between network organization and memory across pathology and cognitive stages in AD remain elusive. We determined whether and how the influences of individual-level structural and met...

The development of in vivo biomarkers of Alzheimer’s disease (AD) has advanced the diagnosis of AD from a clinical syndrome to a biological construct. The preclinical stage of AD continuum is defined by the identification of AD biomarkers crossing the pathological threshold in cognitively unimpaired individuals. While neuropsychiatric symptoms (NPS...

Background The amyloid‐tau‐neurodegeneration (ATN) scheme enables unbiased biomarker‐based diagnoses, independent of cognitive status and temporal ordering of AD pathogenic mechanisms [Jack et al.,2016]. ATN profiles in the diverse Southeast‐Asian region will provide important insights into the ATN framework and its association with cognition [Hila...

Background Southeast Asia represents 10% of the global population, yet little is known about regional clinical characteristics of dementia and risk factors for dementia progression. This study aims to describe the clinico-demographic profiles of dementia in Southeast Asia and investigate the association of onset-type, education, and cerebrovascular...

Background: There is an urgent need for non-invasive, cost-effective biomarkers for Alzheimer’s disease (AD), such as blood-based biomarkers. It is not only to support clinical diagnosis of dementia, but also to allow for timely pharmacological and non-pharmacological interventions evaluation. The aim of this study is to identify and validate a nov...

Background The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH an...

Background: According to the amyloid, tau, neurodegeneration research framework classification, amyloid and tau positive (A+T+) mild cognitive impairment (MCI) individuals are defined as prodromal Alzheimer disease. This study was designed to compare the clinical and biomarker features between A+T+MCI individuals who progressed to progressive MCI...

Background Mild behavioral impairment (MBI) describes persistent behavioral changes in later life as an at-risk state for dementia. While cardiovascular risk factors (CVRFs) are linked to dementia, it is uncertain how CVRFs are associated with MBI. Objective To determine the prevalence of MBI and its association with CVRFs among cognitively normal...

Background Cerebrospinal fluid t-tau (CSF t-tau) is a measure of neurodegeneration in Alzheimer’s disease (AD) and has been increasingly demonstrated to be a non-specific biomarker within the AD continuum. Objective We sought to test whether t-tau influences the longitudinal effects of amyloid-β (Aβ) and phospho-tau (p-tau) on memory and executive...

Neuroimaging measures of Alzheimer's disease (AD) include grey matter volume (GMV) alterations in the Default Mode Network (DMN) and Executive Control Network (ECN). Small-vessel cerebrovascular disease, often visualised as white matter hyperintensities (WMH) on MRI, is often seen in AD. However, the relationship between WMH load and GMV needs furt...

To investigate patterns of hippocampal subfield atrophy among patients with amnestic mild cognitive impairment, stratified by severity of small vessel disease (SVD) and corresponding associations with cognitive domains. One hundred seventy-six MCI subjects (mean age = 65.56 years, SD = 8.77) underwent neuropsychological assessments and magnetic res...

Covering the spectrum of cognitive decline in aging using illustrative cases, from mild impairment to dementia, this set of case studies offers a wide-ranging guide for trainees and clinicians. This second volume includes updated research diagnostic criteria and details of new imaging technology, including novel biomarkers such as PET amyloid and t...

Covering the spectrum of cognitive decline in aging using illustrative cases, from mild impairment to dementia, this set of case studies offers a wide-ranging guide for trainees and clinicians. This second volume includes updated research diagnostic criteria and details of new imaging technology, including novel biomarkers such as PET amyloid and t...

Background Rivastigmine is used to treat cognitive impairment in Alzheimer’s disease (AD); however, the efficacy of Rivastigmine in patients with AD and concomitant small vessel cerebrovascular disease (svCVD) remains unclear. We investigated the effectiveness of Rivastigmine Patch in patients with AD and svCVD. Methods In this open-label study, 1...

Background Persons with mild stroke experience minimal functional difficulties; nonetheless, they are at elevated risk for post-stroke cognitive impairment (PSCI) and cognitive decline. Aims We report outcomes from an observational cohort study of a structured, multidomain intervention for persons with mild strokes. Methods The Stroke Memory Rehabi...

The COVID-19 pandemic has caused tremendous suffering for patients with dementia and their caregivers. We conducted a survey to study the impact of the pandemic on patients with mild frontotemporal dementia (FTD). Our preliminary findings demonstrate that patients with FTD have significant worsening in behavior and social cognition, as well as suff...

Dementia research is critical to improve dementia care; however, participation in this research remains limited, and recruitment is challenging. During an international panel at the 2018 Alzheimer Disease International Conference in Chicago, presentations were given to raise the profile of dementia research and share the patient experience of resea...

Background: Small-vessel cerebrovascular disease often represented as white matter hyperintensities on magnetic resonance imaging, is considered an important risk factor for progression to dementia. Grey matter volume alterations in Alzheimer’s disease-specific regions comprising the default mode network and executive control network are also key f...

Background Young‐onset dementia (YOD) is defined as dementia with symptom onset below 65 years. The heterogeneous symptomatology of YOD can lead to delayed recognition and referral by primary care physicians (PCPs). Data from our tertiary referral centre in Singapore show that atypical presentations of YOD are more likely be referred and diagnosed...

Background Mild Behavioural Impairment (MBI) is a neurobehavioral syndrome characterized by later‐life emergent and sustained neuropsychiatric symptoms that is associated with higher risk of incident cognitive decline and dementia. While MBI is common in both subjective and mild cognitive impairment (MCI), most findings are based on Caucasians and...

Background Mild Behavioural Impairment‐Checklist (MBI‐C) is a validated questionnaire that measures sustained later‐life emergent neuropsychiatric symptoms among people with prodromal dementia. Using this checklist as a MBI case ascertainment instrument, the prevalence of MBI was found to be 5.8% in subjective cognitive decline (SCD) and 14.2% in m...

Background Posterior Cortical Atrophy (PCA) has been widely studied internationally, but there is limited data on its clinical and biomarker characteristics among Southeast Asians. We aim to describe a case series of PCA patients in this part of the world and explore how the new PCA consensus classification (Crutch et al., 2017) could be applied in...

Background Emerging evidence suggests that confluent WMH results in greater cognitive impairment compared to non‐confluent WMH. However, the mechanism linking confluent WMH and early cognitive impairment is not clearly understood. We studied the effects of confluent and non‐confluent WMH on whole‐brain functional connectivity (FC) across 164 region...

Background Hypertension and white matter hyperintensity(WMH) burden are major risk‐factors for Alzheimer’s disease[Pantoni et al.,2010;Sweeney et al.,2018]. Prior studies show variable grey matter alterations, involving both negative and positive associations, independently related to WMH and hypertension in early stages of late‐onset AD[Vipin et a...

Background: White matter hyperintensities (WMHs) indicate active small vessel disease. Emerging evidence suggests that confluent WMH (C-WMH) results in greater cognitive impairment compared with nonconfluent WMH (NC-WMH) visualized as punctate lesions. However, the mechanism linking C-WMH and early cognitive impairment is not clearly understood. A...

To identify knowledge gaps regarding new‐onset agitation and impulsivity prior to onset of cognitive impairment or dementia the International Society to Advance Alzheimer's Research and Treatment Neuropsychiatric Syndromes (NPS) Professional Interest Area conducted a scoping review. Extending a series of reviews exploring the pre‐dementia risk synd...

Background Small vessel disease (SVD) and Alzheimer’s disease (AD) frequently coexist; however, it remains unclear how they collectively affect cognition. Objective We investigated associations between SVD and AD biomarkers, namely amyloid, tau, and neurodegeneration (ATN) in young onset dementia (YOD) and explored how SVD and ATN interact to affe...

Background Neuropsychiatric symptoms (NPS) are increasingly recognized as early non-cognitive manifestations in the Alzheimer’s disease (AD) continuum. However, the role of NPS as an early marker of pathophysiological progression in AD remains unclear. Dominantly inherited AD (DIAD) mutation carriers are young individuals who are destined to develo...

Background Neuropsychiatric symptoms (NPS) are increasingly recognized as early non-cognitive manifestations in the Alzheimer’s disease (AD) continuum. However, the role of NPS as an early marker of pathophysiological progression in AD remains unclear. Dominantly inherited AD (DIAD) mutation carriers are young individuals who are destined to develo...

Background: Neuropsychiatric symptoms (NPS) are increasingly recognized as early non-cognitive manifestations in the Alzheimer’s disease (AD) continuum. However, the role of NPS as an early marker of pathophysiological progression in AD remains unclear. Dominantly inherited AD (DIAD) mutation carriers are young individuals who are destined to devel...

Background: Neuropsychiatric symptoms (NPS) are increasingly recognized as early non-cognitive manifestations in the Alzheimer’s disease (AD) continuum. However, the role of NPS as an early marker of pathophysiological progression in AD remains unclear. Dominantly inherited AD (DIAD) mutation carriers are young individuals who are destined to devel...

Background: Chronic cerebrovascular pathology accelerates the incidence of poststroke dementia (PSD). Whether the risk of PSD varies according to different types of chronic cerebrovascular pathology remains unclear. Objectives: We investigated whether PSD is associated with a unique pattern of interactions between chronic cerebrovascular patholo...

Background Hypertension and white matter hyperintensities (WMH) are mutually associated risk factors for cognitive impairment. However, age may modify the associations between hypertension and WMH, and their links to cognitive impairment. Objective We evaluated the interaction between age and hypertension on WMH, and the age-stratified association...

Background and purpose Accumulated failures in Alzheimer’s disease (AD) clinical trials have highlighted an urgent need to identify additional biomarkers involved in AD. Recently, mounting evidence reported that autoantibodies are ubiquitous in human sera. However, whether autoantibodies are upregulated in amyloid‐tau biomarker confirmed AD is unkn...

Microbleeds are a marker of cerebrovascular disease however its role in incident post-stroke dementia (PSD) remains unclear. We investigated whether microbleeds are associated with incident PSD, domain-specific cognitive impairment and cognitive decline over a 2-year follow- up; and whether microbleeds interact with acute stroke-related infarcts to...

This is a case report of an atypical presentation of early onset Alzheimer disease (EOAD) in a young patient with Capgras syndrome and cognitive impairment. The concurrent onset of psychiatric and cognitive symptoms prompted a detailed evaluation for a neurodegenerative disease. A 50-year-old male lawyer presented with low mood, apathy, delusions,...

Background Cerebral small vessel disease (SVD) and neuropsychiatric symptoms (NPS) independently increase the risk of cognitive decline. While their co-existence has been reported in the preclinical stage of dementia, longitudinal data establishing the prognosis of their associations, especially in an Asian context remains limited. Objective This...

Background: Cerebrovascular disease (CVD) and Alzheimer’s disease (AD) frequently coexist however the mechanism by which they collectively affect cognition remains unclear, particularly in young onset dementia (YOD). We investigated associations between CVD and AD biomarkers, namely amyloid, tau and neurodegeneration (ATN) in YOD, and explored how...

Beginning in the early stages of Alzheimer’s disease (AD), the hippocampus reduces its functional connections to other cortical regions due to synaptic depletion. However, little is known regarding connectivity abnormalities within the hippocampus. Here, we describe rostral-caudal hippocampal convergence (rcHC), a metric of the overlap between the...

Neuropsychiatric symptoms (NPS) including behavioral and psychiatric symptoms are common in the dementia stages of Alzheimer's disease (AD) and are associated with poorer outcomes in cognition, functional states, quality of life, and accelerated progression to severe dementia or death. NPS are also increasingly observed in the mild cognitive impair...