Criteria For Mild Cognitive Impairment Research Articles

The criteria used to rule out mild cognitive impairment impact dementia incidence rates in subjective cognitive decline

BackgroundThe research criteria for subjective cognitive decline (SCD) exclude mild cognitive impairment (MCI), but do not stipulate the use of specific MCI criteria. This study compared different approaches to defining (i.e., excluding) MCI during the ascertainment of SCD, focusing on the impact on dementia incidence rates in SCD.MethodsThis cohort study utilized routine healthcare data collected in the Essex Memory Clinic from 1999 to 2023. Two different operationalizations of the SCD criteria were used to categorize the cohort into two SCD patient samples. One sample was based on local clinical practice – MCI was excluded according to the Winblad criteria (this sample was termed SCDWinblad). The other sample was created via the retrospective application of the Jak/Bondi criteria for the exclusion of MCI (termed SCDJak/Bondi). Only patients aged ≥ 55 years at baseline with ≥ 12 months follow-up were considered for inclusion. The initial clinical/demographic characteristics of the samples were compared. Rates of incident dementia were calculated for each sample, and unadjusted and Mantel-Haenszel-adjusted incidence rate ratios were calculated to compare dementia incidence between the SCD samples.ResultsThe Essex Memory Clinic database included 2,233 patients in total. The SCD and study eligibility criteria were used to select SCDWinblad (n = 86) and SCDJak/Bondi (n = 185) samples from the database. Median follow-up (3 years) did not differ between the two samples. The SCDJak/Bondi sample was significantly older than the SCDWinblad at first assessment (median age: 74 versus 70 years) and had poorer scores on tests of global cognition, immediate and delayed verbal recall, and category fluency. Following adjustment for age, the dementia incidence rate ratio [95% confidence interval] was 3.7 [1.5 to 9.3], indicating a significantly greater rate of progression to dementia in SCDJak/Bondi.ConclusionsThis study highlights that the approach used to ascertain SCD has important implications for both SCD phenotypes and prognosis. This underscores the importance of how MCI is operationalized within SCD studies. More broadly, the findings add to a growing body of work indicating that objective cognition should not be overlooked in SCD, and offer a potential explanation for the heterogeneity across the SCD prognostic literature.

Data-driven sequence of cognitive decline in people with Parkinson’s disease

BackgroundUnderstanding the sequential progression of cognitive impairments in Parkinson’s disease (PD) is crucial for elucidating neuropathological underpinnings, refining the assessment of PD-related cognitive decline stages and enhancing early identification for...

The prevalence of mild cognitive impairment in breast cancer patients receiving chemotherapy according to the criteria of the National Institute on Aging-Alzheimer's Association (NIA-AA).

Breast cancer patients receiving chemotherapy can develop cognitive impairment. There is no gold standard for defining cognitive impairment. We applied the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) to determine its prevalence in breast cancer patients receiving adjuvant chemotherapy and examine differences between patients with and without MCI. We used pre-existing cognitive data on 5 neuropsychological test outcomes (verbal memory, processing speed, executive functioning, and verbal fluency) gathered from 240 breast cancer patients who received adjuvant conventional (n = 154) or high-dose chemotherapy (n = 86). Assessments occurred 6 or 12months post-chemotherapy and results were compared with data from 66 women without cancer. MCI was defined by the following: (i) presence of concern regarding a change in cognition, (ii) impairment in one or more cognitive tests (1.5 standard deviation below a normative mean), (iii) preservation of independence in functional abilities, and (iv) the absence of dementia. Twenty percent (n = 49) of breast cancer patients who received chemotherapy (conventional therapy n = 29 (12%), high-dose therapy = 20 (8.3%)) met the criteria for MCI, compared with 7.6% (n = 5) of controls. Prevalence was significantly different between patients and controls (P = 0.020, and corrected for IQ P < 0.001). Patients with MCI had significant lower education levels (P < 0.002) and premorbid IQ (P = 0.001) compared with patients without MCI. Twenty percent of breast cancer patients treated with chemotherapy met NIA-AA criteria for MCI, compared with 7.6% of the controls. These criteria, which include formal test performance as well as a person's symptoms and functional status, can be useful in clinical practice and scientific research.

Validity of Montreal Cognitive Assessment to Detect Cognitive Impairment in Individuals with Type 2 Diabetes.

Guidelines recommend screening older people (> 60-65years) with type 2 diabetes (T2D) for cognitive impairment, as it has implications in the management of diabetes. The Montreal Cognitive Assessment (MoCA) is a sensitive test for the detection of mild cognitive impairment (MCI) in the general population, but its validity in T2D has not been established. We administered MoCA to patients with T2D (age ≥ 60years) and controls (no T2D), along with a culturally validated neuropsychological battery and functional activity questionnaire. MCI was defined as performance in one or more cognitive domains ≥ 1.0 SD below the control group (on two tests representing a cognitive domain), with preserved functional activities. The discriminant validity of MoCA for the diagnosis of MCI at different cut-offs was ascertained. We enrolled 267 patients with T2D and 120 controls; 39% of the participants with T2D met the diagnostic criteria for MCI on detailed neuropsychological testing. At the recommended cut-off on MoCA (< 26), the sensitivity (94.2%) was high, but the specificity was quite low (29.5%). The cut-off score of < 23 showed an optimal trade-off between sensitivity (69.2%), specificity (71.8%), and diagnostic accuracy (70.8%). The cut-off of < 21 exhibited the highest diagnostic accuracy (74.9%) with an excellent specificity (91.4%), a good positive and negative predictive value (78.5% and 73.7%, respectively). The recommended screening cut-off point on MoCA of < 26 has a suboptimal specificity and may increase the referral burden in memory clinics. A lower cut-off of < 21 on MoCA maximizes the diagnostic accuracy. Interactive Visual Abstract available for this article.

Discriminant Potential of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) in Greek Older Adults with Subjective Cognitive Decline and Mild Cognitive Impairment.

Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) is a widely used screening tool for detecting older adults with Alzheimer's disease among their cognitively healthy peers. A previous study in Greek population showed that ADAS-Cog-Greek (G) is a valid tool and can identify people with Alzheimer's disease from older adult control group; however, there is no current data about whether ADAS-Cog can differentiate older adults with mild cognitive impairment (MCI) from those who have subjective cognitive decline (SCD). The current study aimed to examine the discriminant potential of ADAS-Cog-G in Greek older adults who meet the criteria for SCD or MCI. Four hundred eighty-two community-dwelling older adults, visitors of the Greek Alzheimer Association and Related Disorders, were enrolled in the current study. One hundred seventy-six of them met the criteria for SCD and three hundred six had MCI. Path analysis applied to the data showed that age, as well as educational level affected ADAS-Cog-G performance. Results showed that the cut-off scores, which better discriminate people with SCD from MCI as well as their sensitivity and specificity values, were extracted in participants with high educational level (13 educational years<) and mainly under the age of 75 years. The current study provided evidence concerning the discriminant potential of ADAS-Cog-G to differentiate older adults with SCD from those with MCI in the Greek population, and therefore contributes to the relevant literature on the field.

Cognitive Impairment Is Part of the Phenotype of Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS).

Little is known about the impact of the cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) on cognition. Our objective was to determine the frequency and severity of cognitive impairment in RFC1-positive patients and describe the pattern of deficits. Participants underwent a comprehensive neuropsychological assessment. Volume of the cerebellum and its lobules was measured in those who underwent a 3 Tesla-magnetic resonance scan. Twenty-one patients underwent a complete assessment, including 71% scoring lower than the cutoff at the Montreal Cognitive assessment and 71% having a definite cerebellar cognitive affective/Schmahmann syndrome. Three patients had dementia and seven met the criteria of mild cognitive impairment. Severity of cognitive impairment did not correlate with severity of clinical manifestations. Performance at memory and visuospatial functions tests negatively correlated with the severity of cerebellar manifestations. Cognitive manifestations are frequent in RFC1-related disorders. They should be included in the phenotype and screened systematically. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Abnormal functional connectivity of the occipital thalamus with the superior occipital gyrus is associated with mild cognitive impairment in elderly individuals with primary insomnia

AbstractStudy objectivesPrimary insomnia (PI) triggers a decline in cognitive function, and the thalamus plays an integral role in this process; however, the mechanisms are unclear. The purpose of this study was to investigate the altered functional connectivity (FC) of the thalamus in PI patients with mild cognitive impairment (MCI) and to explore the potential neural mechanisms of thalamic involvement in these patients.MethodsThis case–control study was conducted in older adults from various communities in Fuzhou, China with a PI diagnosis. These participants underwent neuropsychological assessment and were matched in a 1:2 ratio to the healthy control (HC) group and the PI group according to sex, age, and education level. Resting‐state functional magnetic resonance imaging was used to explore changes in thalamic FC in PI patients. To further compare changes in thalamic and whole‐brain FC, we further divided the PI group into cognitively normal patients and patients with MCI according to the diagnostic criteria for MCI. The relationship between abnormal FC and cognitive function was investigated.ResultsThe 28 HCs and 58 participants with PI showed significant differences in Montreal Cognitive Assessment (MoCA) scores (p = .044). In comparison to the HC group, the PI group showed enhanced FC of the occipital thalamus with the left inferior occipital gyrus, right lingual gyrus, left middle temporal gyrus, left superior marginal gyrus, left dorsolateral superior frontal gyrus, and right anterior central gyrus. The MoCA total score and the executive function, attention, and abstraction scores of PI patients with MCI (PI–MCI) were worse than those of PI patients without MCI. In comparison to the simple PI group, FC was enhanced in the PI–MCI group between the left occipital thalamus and the middle occipital gyrus, and between the right occipital thalamus and the right superior frontal gyrus, left middle frontal gyrus, right superior occipital gyrus, and orbital inferior frontal gyrus. There was a significant negative correlation between the MoCA total score and the enhanced FC between the right occipital thalamus and right superior occipital gyrus (r = −.419, p = .042).ConclusionThe early onset of cognitive impairment in patients with PI is associated with altered FC between the thalamus and the cortex. Enhanced FC between the thalamus and the visual cortex, that is, the superior occipital gyrus, which is involved in attentional processing, may play a role in the early onset of cognitive impairment in insomnia patients. Moreover, due to the fact that PI patients “overdraw” the compensatory capacity of these brain regions earlier, the PI–MCI may fall into the abyss of “decompensation” faster and face more severe cognitive impairments.

Comparing neuropsychological, typical, and ADNI criteria for the diagnosis of mild cognitive impairment in Vietnam-era veterans.

Neuropsychological criteria for mild cognitive impairment (MCI) more accurately predict progression to Alzheimer's disease (AD) and are more strongly associated with AD biomarkers and neuroimaging profiles than ADNI criteria. However, research to date has been conducted in relatively healthy samples with few comorbidities. Given that history of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for AD and common in Veterans, we compared neuropsychological, typical (Petersen/Winblad), and ADNI criteria for MCI in Vietnam-era Veterans with histories of TBI or PTSD. 267 Veterans (mean age = 69.8) from the DOD-ADNI study were evaluated for MCI using neuropsychological, typical, and ADNI criteria. Linear regressions adjusting for age and education assessed associations between MCI status and AD biomarker levels (cerebrospinal fluid [CSF] p-tau181, t-tau, and Aβ42) by diagnostic criteria. Logistic regressions adjusting for age and education assessed the effects of TBI severity and PTSD symptom severity simultaneously on MCI classification by each criteria. Agreement between criteria was poor. Neuropsychological criteria identified more Veterans with MCI than typical or ADNI criteria, and were associated with higher CSF p-tau181 and t-tau. Typical and ADNI criteria were not associated with CSF biomarkers. PTSD symptom severity predicted MCI diagnosis by neuropsychological and ADNI criteria. History of moderate/severe TBI predicted MCI by typical and ADNI criteria. MCI diagnosis using sensitive neuropsychological criteria is more strongly associated with AD biomarkers than conventional diagnostic methods. MCI diagnostics in Veterans would benefit from incorporation of comprehensive neuropsychological methods and consideration of the impact of PTSD.

Mild cognitive impairment in Huntington's disease: challenges and outlooks.

Although Huntington's disease (HD) has classically been viewed as an autosomal-dominant inherited neurodegenerative motor disorder, cognitive and/or behavioral changes are predominant and often an early manifestation of disease. About 40% of individuals in the presymptomatic period of HD meet the criteria for mild cognitive impairment, later progressing to dementia. The heterogenous spectrum of cognitive decline is characterized by deficits across multiple domains, particularly executive dysfunctions, but the underlying pathogenic mechanisms are still poorly understood. Investigating the pathophysiology of cognitive changes may give insight into important and early neurodegenerative events. Multimodal imaging revealed circuit-wide gray and white matter degenerative processes in several key brain regions, affecting prefronto-striatal/cortico-basal ganglia circuits and many other functional brain networks. Studies in transgenic animal models indicated early synaptic dysfunction, deficient neurotrophic transport and other molecular changes contributing to neuronal death. Synaptopathy within the cerebral cortex, striatum and hippocampus may be particularly important in mediating cognitive and neuropsychiatric manifestations of HD, although many other neuronal systems are involved. The interaction of mutant huntingtin protein (mHTT) with tau and its implication for cognitive impairment in HD is a matter of discussion. Further neuroimaging and neuropathological studies are warranted to better elucidate early pathophysiological mechanisms and to develop validated biomarkers to detect patients' cognitive status during the early stages of the condition significantly to implement effective preventing or management strategies.

The prevalence of mild cognitive impairment in Gulf War veterans: a follow-up study.

Gulf War Illness (GWI), also called Chronic Multisymptom Illness (CMI), is a multi-faceted condition that plagues an estimated 250,000 Gulf War (GW) veterans. Symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. We previously reported that 12% of a convenience sample of middle aged (median age 52 years) GW veterans met criteria for mild cognitive impairment (MCI), a clinical syndrome most prevalent in older adults (e.g., ≥70 years). The current study sought to replicate and extend this finding. We used the actuarial neuropsychological criteria and the Montreal Cognitive Assessment (MoCA) to assess the cognitive status of 952 GW veterans. We also examined regional brain volumes in a subset of GW veterans (n = 368) who had three Tesla magnetic resonance images (MRIs). We replicated our previous finding of a greater than 10% rate of MCI in four additional cohorts of GW veterans. In the combined sample of 952 GW veterans (median age 51 years at time of cognitive testing), 17% met criteria for MCI. Veterans classified as MCI were more likely to have CMI, history of depression, and prolonged (≥31 days) deployment-related exposures to smoke from oil well fires and chemical nerve agents compared to veterans with unimpaired and intermediate cognitive status. We also replicated our previous finding of hippocampal atrophy in veterans with MCI, and found significant group differences in lateral ventricle volumes. Because MCI increases the risk for late-life dementia and impacts quality of life, it may be prudent to counsel GW veterans with cognitive dysfunction, CMI, history of depression, and high levels of exposures to deployment-related toxicants to adopt lifestyle habits that have been associated with lowering dementia risk. With the Food and Drug Administration's recent approval of and the VA's decision to cover the cost for anti-amyloid β (Aβ) therapies, a logical next step for this research is to determine if GW veterans with MCI have elevated Aβ in their brains.

Preventing cognitive decline by reducing BP target (PCOT): A randomized, pragmatic, multi-health systems clinical trial

BackgroundGrowing evidence suggests that intensive lowering of systolic blood pressure (BP) may prevent mild cognitive impairment (MCI) and dementia. However, current guidelines provide inconsistent recommendations regarding optimal BP targets, citing safety concerns of excessive BP lowering in the diverse population of older adults. We are conducting a pragmatic trial to determine if an implementation strategy to reduce systolic BP to <130 and diastolic BP to <80 mmHg will safely slow cognitive decline in older adults with hypertension when compared to patients receiving usual care. MethodsThe Preventing Cognitive Decline by Reducing BP Target Trial (PCOT) is an embedded randomized pragmatic clinical trial in 4000 patients from two diverse health-systems who are age ≥ 70 years with BP >130/80 mmHg. Participants are randomized to the intervention arm or usual care using a permuted block randomization within each health system. The intervention is a combination of team-based care with clinical decision support to lower home BP to <130/80 mmHg. The primary outcome is cognitive decline as determined by the change in the modified Telephone Interview for Cognitive Status (TICS-m) scores from baseline. As a secondary outcome, patients who decline ≥3 points on the TICS-m will complete additional cognitive assessments and this information will be reviewed by an expert panel to determine if they meet criteria for MCI or dementia. ConclusionThe PCOT trial will address the effectiveness and safety of hypertension treatment in two large health systems to lower BP targets to reduce risk of cognitive decline in real-world settings.

Data-driven retrieval of population-level EEG features and their role in neurodegenerative diseases.

Electrophysiologic disturbances due to neurodegenerative disorders such as Alzheimer's disease and Lewy Body disease are detectable by scalp EEG and can serve as a functional measure of disease severity. Traditional quantitative methods of EEG analysis often require an a-priori selection of clinically meaningful EEG features and are susceptible to bias, limiting the clinical utility of routine EEGs in the diagnosis and management of neurodegenerative disorders. We present a data-driven tensor decomposition approach to extract the top 6 spectral and spatial features representing commonly known sources of EEG activity during eyes-closed wakefulness. As part of their neurologic evaluation at Mayo Clinic, 11 001 patients underwent 12 176 routine, standard 10-20 scalp EEG studies. From these raw EEGs, we developed an algorithm based on posterior alpha activity and eye movement to automatically select awake-eyes-closed epochs and estimated average spectral power density (SPD) between 1 and 45 Hz for each channel. We then created a three-dimensional (3D) tensor (record × channel × frequency) and applied a canonical polyadic decomposition to extract the top six factors. We further identified an independent cohort of patients meeting consensus criteria for mild cognitive impairment (30) or dementia (39) due to Alzheimer's disease and dementia with Lewy Bodies (31) and similarly aged cognitively normal controls (36). We evaluated the ability of the six factors in differentiating these subgroups using a Naïve Bayes classification approach and assessed for linear associations between factor loadings and Kokmen short test of mental status scores, fluorodeoxyglucose (FDG) PET uptake ratios and CSF Alzheimer's Disease biomarker measures. Factors represented biologically meaningful brain activities including posterior alpha rhythm, anterior delta/theta rhythms and centroparietal beta, which correlated with patient age and EEG dysrhythmia grade. These factors were also able to distinguish patients from controls with a moderate to high degree of accuracy (Area Under the Curve (AUC) 0.59-0.91) and Alzheimer's disease dementia from dementia with Lewy Bodies (AUC 0.61). Furthermore, relevant EEG features correlated with cognitive test performance, PET metabolism and CSF AB42 measures in the Alzheimer's subgroup. This study demonstrates that data-driven approaches can extract biologically meaningful features from population-level clinical EEGs without artefact rejection or a-priori selection of channels or frequency bands. With continued development, such data-driven methods may improve the clinical utility of EEG in memory care by assisting in early identification of mild cognitive impairment and differentiating between different neurodegenerative causes of cognitive impairment.

The interaction of obesity with susceptible gene polymorphisms in the relationship with mild cognitive impairment.

Mild cognitive impairment (MCI) in the elderly is threatening the mental health of the elderly, and the interaction of some factors is worth exploring. This study aims to explore the interactions of obesity and gene polymorphisms in the relationship with MCI. A total of 2555 community resident dwellings include 444 participants who met MCI criteria recruited from the Ningxia province of China. Fourteen MCI-susceptible single nucleotide polymorphisms were detected using a high-throughput mass spectrometer. The interaction was examined by performing the multifactor dimensionality reduction model and unconditional logistic regression model. Logistic regression showed that obesity (OR = 1.42, 95%CI: 1.04-1.94), rs2075650G allele carrying (OR = 17.95, 95%CI: 1.32-244.95), rs11556505T allele carrying (OR = 0.06, 95%CI: 0.01-0.87) were statistically associated with MCI. Multifactor dimensionality reduction analysis showed a strong antagonistic effect between obesity and rs4402960 (Interaction dendrogram between obesity and rs4402960 is red) and a weak synergy effect on rs7901695 (Interaction dendrogram between obesity and rs7901695 is green). The hierarchical analysis showed obesity is a risk factor for MCI in the non-rs4402960T allele carrier group (OR = 1.55, 95%CI: 1.02-2.35). This study found that obesity is an independent risk factor for MCI, and the interactions with MCI-susceptible gene polymorphisms suggest a possible precision preventive intervention program should be developed to reduce the risk of MCI among individuals with obesity in the community.

Yerba mate (Ilex paraguariensis) consumption and risk of cognitive impairment: a prospective study project

AbstractBackgroundAging is the main risk factor for neurodegenerative diseases, such as Alzheimer’s disease (AD) dementia. Yerba mate (YM) tea or mate Ilex paraguariensis is an infusion widely consumed in Argentina and other South American countries such as Brazil, Paraguay, and Uruguay. Experimental studies suggest a YM antioxidant and protective effect against amyloid deposition in AD. Previously, our group and others identified an inverse association between YM consumption and Parkinson’s Disease. The aim of this project is to evaluate a potential association between YM consumption and the risk of cognitive impairment development.MethodTwo different stages were designed. Stage I is a descriptive study designed. Adult patients fulfilling mild cognitive impairment criteria (MCI) evaluated at the Sanatorio de la Trinidad Mitre between January 2021 and December 2022 will be included. Each participant or their caregiver will be invited to complete a survey about lifestyle and nutritional information, including YM consumption. Stage II is a case‐control study. Patients with MCI will be distributed by severity and subtypes of MCI. The control group will be constituted by individuals with normal cognitive evaluations matched by age, sex and educational level who agree to answer the afore mentioned survey. All data will be recorded in an anonymized electronic database and statistical analysis will be carried out. Project duration is estimated at 12 months for each stage.ResultResults from stage I will describe epidemiological and clinical characteristics of patients with MCI and the frequency and duration of YM consumption in this group of patients, as well as any potential correlation between neuropsychological tests and YM consumption. Results from stage II are expected to identify an inverse association between the magnitude of YM consumption and MCI.ConclusionObservational evidence of the association between YM consumption and MCI might be the first step to develop experimental studies using Ilex paraguariensis in neurodegenerative cognitive disorders.

Loneliness and daily subjective cognitive concerns among cognitively normal older adults and individuals with MCI

AbstractBackgroundLoneliness is associated with increased dementia risk and is bidirectionally associated with cognitive decline across several years. Less is known about how loneliness and cognitive function are bidirectionally related on shorter timescales. This study examined daily associations between loneliness and self‐reported cognitive concerns in cognitively normal older adults and those with mild cognitive impairment (MCI).MethodCommunity‐dwelling older adults from the Einstein Aging Study (n = 311, age 70‐90 years, 65.9% female, 41.8% Black/African American, 12.5% Hispanic, 30.9% met Jak/Bondi criteria for MCI) completed a two week ecological momentary assessment (EMA) protocol via smartphone. Participants rated their current feelings of loneliness up to 5 times per day (4 via notifications, and 1 at end of day). These ratings were averaged to obtain a loneliness severity score for each day. Subjective cognitive concerns (prospective and retrospective memory lapses, attention/executive function difficulties) were assessed at the end of each day. Participants also reported how much each concern bothered them and/or disrupted their daily activities. Multilevel models were used to assess same‐day and next‐day associations between loneliness and each of the subjective cognitive concern outcomes bidirectionally.ResultsThere were bidirectional same‐day associations observed between loneliness severity and greater number and more bother of attention/executive concerns, as well as greater disruption of all cognitive concerns. When considering associations of present day loneliness with next day cognitive concerns, greater severity of loneliness predicted more bother of attention/executive concerns on the following day. Additionally, present day number of attention/executive concerns and disruption of all cognitive concerns predicted next day loneliness severity. All effects remained significant after adjusting for age, sex, years of education, and MCI status.ConclusionThese findings demonstrate that loneliness is dynamically associated with attention and executive function, but not memory lapses, on a day‐to‐day basis. Associations between loneliness and experience of bother and disruption due to cognitive concerns, suggest that loneliness may signal greater severity of, or less ability to cope with, cognitive difficulties.

Within‐Day Variability in Mobile Cognitive Assessments: Associations with Mild Cognitive Impairment and Sociodemographic Factors

AbstractBackgroundGreater within‐person variability in cognitive performance on mobile devices is emerging as a sensitive marker of mild cognitive impairment (MCI). It is unclear if sociodemographic differences are associated with this variability, and if so, whether these differences moderate associations between MCI status and within‐person variability. We use a digital health approach with ecological momentary assessments (EMA) to examine sociodemographic differences in within‐day variability among individuals with MCI and those who were cognitively unimpaired (CU).MethodA sample of 308 community‐dwelling older adults from the Einstein Aging Study (mean age = 77.49 years, SD = 4.86, range = 70‐90; 67% female; 45% non‐Hispanic White, 41% non‐Hispanic Black) completed neuropsychological testing and self‐reported questionnaires. Ninety‐eight individuals met Jak/Bondi criteria for MCI. All participants performed mobile tests of processing speed and memory binding on a smartphone up to six times daily over a two‐week period. We employed heterogeneous variance multilevel models to assess sociodemographic and MCI status associations with within‐day variability across assessments. We further tested whether differences in age, gender, race, and education moderated associations between MCI status and within‐day variability.ResultFor processing speed, greater variability was apparent in individuals with MCI, non‐Hispanic Black participants, and individuals with less education (ps&lt;.001). A MCI status*gender interaction occurred; the association between MCI status and variability remained significant for both genders but was smaller among women (p&lt;.01). For memory binding, greater variability was apparent in individuals with MCI, older participants, non‐Hispanic Black participants, and individuals with less education (ps&lt;.001). Numerous interactions occurred; in separate analyses, associations between MCI status and variability remained significant, but were smaller among women, non‐Hispanic Black participants, and individuals with less education (ps&lt;.05).ConclusionIndividuals with MCI exhibited greater within‐day variability in mobile cognitive performance than those who were CU, but the strength of these associations varied by sociodemographic factors. These indices of variability in everyday life may serve as sensitive markers of early cognitive impairment. Future research should examine daily mechanisms and environmental perturbations (e.g., stress, sleep, air pollution) that may explain why associations between MCI status and cognitive variability appeared smaller among women, non‐Hispanic Black participants, and individuals with less education.

Detection of PART in vivo using tau‐PET: preliminary findings using [18F]RO948

AbstractBackgroundPrimary age‐related tauopathy (PART) is a neuropathological entity describing tau pathology in the entorhinal cortex and hippocampus in the absence of amyloid‐β (Aβ) plaques. Though cross‐sectional work using [18F]flortaucipir tau‐PET has shown an association between medial temporal lobe signal and worse cognitive performance, longitudinal studies are needed to examine whether medial temporal lobe tau is associated with cognitive decline and cortical tau accumulation in cognitively unimpaired (CU) individuals. We here aimed to investigate whether CU individuals who are Aβ‐negative and tau‐PET positive in the medial temporal lobe show cognitive decline and increases in CSF phosphorylated tau (P‐tau) or tau PET over time.MethodsUsing BioFINDER‐2, PART was defined as i) CU individuals (not fulfilling criteria for mild cognitive impairment of dementia), ii) age ≥ 60 years, iii) Aβ‐negative (Centiloids &lt; 20 and negative CSF Aβ42/40), and iv) an [18F]RO948 tau‐PET standardized uptake value ratio (SUVR) &gt;1.26 (cut‐off based on Gaussian mixture modelling in BioFINDER‐2, n = 1754) in a volume‐weighted ROI encompassing the entorhinal cortex and hippocampus. [18F]RO948 data was collected 70 to 90 min post‐injection with longitudinal follow‐up collected after ∼2.5 years (average 2.73 ± 1.14 years). Longitudinal P‐tau217 was measured using immunoprecipitation‐mass spectrometry (average 2.67 ± 1.12 years). Longitudinal cognitive measures (average 2.75 ± 0.94 years) included the MMSE and modified PACC. For both longitudinal [18F]RO948, CSF P‐tau217 and cognition, change was assessed using slopes derived from linear mixed models.Results38 individuals fulfilled inclusion criteria (Table 1). These individuals showed significant increases in [18F]RO948 SUVR in the entorhinal cortex/hippocampus (p&lt;0.05, t‐test vs 0)—but not in the temporal cortex—and in CSF P‐tau217 (p&lt;0.01, t‐test vs 0) over time (Figure 1A). This group also showed cognitive decline over time using the PACC (p&lt;0.01, t‐test vs 0) but not the MMSE (Figure 1B). Additional analyses are ongoing using two additional tau‐PET tracers and additional CSF‐based P‐tau measures.ConclusionsThese preliminary findings using [18F]RO948 suggest that PART can be detected in vivo using tau‐PET and that Aβ‐negative CU individuals who are tau‐PET positive in the medial temporal lobe are at risk for focal tau accumulation and cognitive decline.

Classifying Memory Clinic Patients Using the Digital Clock Drawing TestTM, Mini‐Mental State Examination, and Philadelphia (repeatable) Verbal Learning Test

AbstractBackgroundDigital cognitive assessments (DCA) enable quick, sensitive, and reliable assessment of neurocognitive operations that underlie dementia and mild cognitive impairment (MCI). We examined how well the DCTclockTM DCA, Mini‐Mental State Examination (MMSE), and Philadelphia (repeatable) Veral Learning Test (PrVLT) can classify memory clinic patients by cognitive impairment profile.Method106 serial referrals to an outpatient memory clinic were assessed with the DCTclock, MMSE, and P(r)VLT. Using statistical criteria for subtle cognitive impairment (SCI, Edmonds et al., 2015) and MCI (Jak et al., 2008), patients were classified into cognitively normal (CN, n = 21), SCI (n = 33), amnestic MCI (aMCI, n = 22), and dysexecutive/mixed MCI (d/mMCI, n = 30) groups. A series of stepwise logistic regression analyses were conducted with CN participants as the criterion group.ResultIn the first analysis (Table 1), P(r)VLT‐recognition (X2 = 24.39, p&lt;0.001) entered the model first followed by the DCTclock Score (X2 = 16.68, p&lt;0.001). P(r)VLT‐recognition classified aMCI patients (Wald = 11.21, p&lt;0.001). DCTclock (Wald = 8.97, p&lt;0.001) and P(r)VLT‐recognition (Wald = 4.06, p&lt;0.001) classified d/mMCI patients. In the second analysis the four command DCTclock composites were analyzed, excluding the MMSE and P(r)VLT‐recognition scores, Spatial Reasoning classified patients into their respective groups (SCI, Wald = 3.68, p&lt;0.055; aMCI, Wald = 8.84, p&lt;0.003; d/mMCI, Wald = 19.12 p&lt;0.001). Third, analyzing DCTclock command Spatial Reasoning, MMSE, and P(r)VLT‐recognition, the P(r)VLT score, again, entered first (X2 = 24.39, p&lt;0.001) followed by DCTclock Spatial Reasoning (X2 = 18.95, p&lt;0.001). DCTclock Spatial Reasoning classified SCI patients (Wald = 4.66, p&lt;0.031), P(r)VLT‐recognition classified aMCI patients (Wald = 9.11, p&lt;0.003), and both DCTclock command Spatial Reasoning (Wald = 10.56, p&lt;0.001) and P(r)VLT‐recognition (Wald = 3.32, p&lt;.068) classified d/mMCI patients.ConclusionUnlike the MMSE that takes 10‐15 minutes to administer and is scored subjectively, all DCTclock data are digitally obtained and automatically scored, requiring no examiner interface for administration and interpretation, thus obviating clinical judgment, ensuring inter‐rater reliability, and enabling more efficient cognitive assessments. In this series of logistic regression analyses, a combination of DCTclock and P(r)VLT clearly outperformed the MMSE in classifying non‐demented memory clinic patients into cognitively normal, subtle cognitive impairment, and MCI subtypes. These results support the efficacy of DCAs in clinical trials and to screen for emergent cognitive impairment in primary care and specialty medical practices.

Classifying Memory Clinic Patients Using the Digital Clock Drawing TestTM, Mini‐Mental State Examination, and Philadelphia (repeatable) Verbal Learning Test

AbstractBackgroundDigital cognitive assessments (DCA) enable quick, sensitive, and reliable assessment of neurocognitive operations that underlie dementia and mild cognitive impairment (MCI). We examined how well the DCTclockTM DCA, Mini‐Mental State Examination (MMSE), and Philadelphia (repeatable) Veral Learning Test (PrVLT) can classify memory clinic patients by cognitive impairment profile.Method106 serial referrals to an outpatient memory clinic were assessed with the DCTclock, MMSE, and P(r)VLT. Using statistical criteria for subtle cognitive impairment (SCI, Edmonds et al., 2015) and MCI (Jak et al., 2008), patients were classified into cognitively normal (CN, n = 21), SCI (n = 33), amnestic MCI (aMCI, n = 22), and dysexecutive/mixed MCI (d/mMCI, n = 30) groups. A series of stepwise logistic regression analyses were conducted with CN participants as the criterion group.ResultIn the first analysis (Table 1), P(r)VLT‐recognition (X2= 24.39, p&lt;0.001) entered the model first followed by the DCTclock Score (X2= 16.68, p&lt;0.001). P(r)VLT‐recognition classified aMCI patients (Wald = 11.21, p&lt;0.001). DCTclock (Wald = 8.97, p&lt;0.001) and P(r)VLT‐recognition (Wald = 4.06, p&lt;0.001) classified d/mMCI patients. In the second analysis the four command DCTclock composites were analyzed, excluding the MMSE and P(r)VLT‐recognition scores, Spatial Reasoning classified patients into their respective groups (SCI, Wald = 3.68, p&lt;0.055; aMCI, Wald = 8.84, p&lt;0.003; d/mMCI, Wald = 19.12 p&lt;0.001). Third, analyzing DCTclock command Spatial Reasoning, MMSE, and P(r)VLT‐recognition, the P(r)VLT score, again, entered first (X2= 24.39, p&lt;0.001) followed by DCTclock Spatial Reasoning (X2= 18.95, p&lt;0.001). DCTclock Spatial Reasoning classified SCI patients (Wald = 4.66, p&lt;0.031), P(r)VLT‐recognition classified aMCI patients (Wald = 9.11, p&lt;0.003), and both DCTclock command Spatial Reasoning (Wald = 10.56, p&lt;0.001) and P(r)VLT‐recognition (Wald = 3.32, p&lt;.068) classified d/mMCI patients.ConclusionUnlike the MMSE that takes 10‐15 minutes to administer and is scored subjectively, all DCTclock data are digitally obtained and automatically scored, requiring no examiner interface for administration and interpretation, thus obviating clinical judgment, ensuring inter‐rater reliability, and enabling more efficient cognitive assessments. In this series of logistic regression analyses, a combination of DCTclock and P(r)VLT clearly outperformed the MMSE in classifying non‐demented memory clinic patients into cognitively normal, subtle cognitive impairment, and MCI subtypes. These results support the efficacy of DCAs in clinical trials and to screen for emergent cognitive impairment in primary care and specialty medical practices.

Spectrum of Neuropsychiatric Symptoms in Southeast Asians with Prodromal Dementia

AbstractBackgroundBehavioral 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 Cognitive Decline(SCD) and Mild Cognitive Impairment(MCI).MethodThis study utilized cross‐sectional data from the Biomarkers and Cognition Study, Singapore(BIOCIS). From February to December 2022, participants who met criteria for SCD and MCI in accordance with NIA‐AA’s criteria were classified into two groups, NPS and without‐NPS, based on clinical cut‐offs of Depression Anxiety Stress Scales(DASS) scores. Self‐reported questionnaires assessed behavioral symptoms ‐ Mild Behavioral Impairment‐Checklist(MBI‐C); Dementia‐Quality of Life Instrument(Dem‐QOL); International Physical Activity Questionnaire(IPAQ); and Pittsburgh Sleep Quality Index(PSQI). Group comparisons of data were applied separately using univariate analyses. A Receiver Operating Characteristic analysis was conducted to test the diagnostic performance of MBI‐C total, MBI‐C‐subdomains, and PSQI in distinguishing participants with NPS and without‐NPS.Result488 participants (μ age = 62.7±9.64,42.2% males) were analyzed. 133(27.25%) reported significant NPS symptoms. Participants with NPS reported significantly more symptoms on MBI‐C‐total(p&lt;.001); interest(p&lt;.001); mood(p&lt;.001); control(p&lt;.001), social(p&lt;.001), and beliefs(p&lt;.001) subdomains; poorer sleep(p&lt;.001) and lower quality of life(p&lt;.001) compared to participants without‐NPS(Table 1). MBI‐C‐total, MBI‐C‐mood and MBI‐C‐control subdomains were effective in discriminating between participants with and without NPS, with an acceptable Area Under the Curve: .782(.732‐.833) for MBI‐C‐total, .753(.699‐.807) for MBI‐C‐mood, and .753(.699‐.807) for MBI‐C‐control(Figure 1 and Table 2).ConclusionIn a prodromal cohort of southeast Asians, participants with NPS reported significantly worse scores on MBI‐C‐total and subdomains, specifically ‐ decreased motivation, emotional dysregulation, impulse control, social inappropriateness, abnormal perceptions, as well as poorer sleep quality and a lower quality of life compared to participants without‐NPS. The results are keeping with the strong evidence that behavioral changes are among the first symptoms noticeable to the person themselves as they begin to experience cognitive decline. The self‐reported questionnaires used are easily administered and brief, which has important real‐world relevance for early diagnoses of, and timely intervention for prodromal dementia. Further studies of BIOCIS is on‐going to investigate the impact of NPS on cognitive decline.