Linking Dementia Pathology and Alteration in Brain Activation to Complex Daily Functional Decline During the Preclinical Dementia Stages: Protocol for a Prospective Observational Cohort Study.

BACKGROUND: Progressive difficulty in performing everyday functional activities is a key diagnostic feature of dementia syndromes. However, not much is known about the neural signature of functional decline, particularly during the very early stages of dementia. Early intervention before overt impairment is observed offers the best hope of reducing the burdens of Alzheimer disease (AD) and other dementias. However, to justify early intervention, those at risk need to be detected earlier and more accurately. The decline in complex daily function (CdF) such as managing medications has been reported to precede impairment in basic activities of daily living (eg, eating and dressing). OBJECTIVE: Our goal is to establish the neural signature of decline in CdF during the preclinical dementia period. METHODS: Gait is central to many CdF and community-based activities. Hence, to elucidate the neural signature of CdF, we validated a novel electroencephalographic approach to measuring gait-related brain activation while participants perform complex gait-based functional tasks. We hypothesize that dementia-related pathology during the preclinical period activates a unique gait-related electroencephalographic (grEEG) pattern that predicts a subsequent decline in CdF. RESULTS: We provide preliminary findings showing that older adults reporting CdF limitations can be characterized by a unique gait-related neural signature: weaker sensorimotor and stronger motor control activation. This subsample also had smaller brain volume and white matter hyperintensities in regions affected early by dementia and engaged in less physical exercise. We propose a prospective observational cohort study in cognitively unimpaired older adults with and without subclinical AD (plasma amyloid-ß) and vascular (white matter hyperintensities) pathologies. We aim to (1) establish the unique grEEG activation as the neural signature and predictor of decline in CdF during the preclinical dementia period; (2) determine associations between dementia-related pathologies and incidence of the neural signature of CdF; and (3) establish associations between a dementia risk factor, physical inactivity, and the neural signature of CdF. CONCLUSIONS: By establishing the clinical relevance and biological basis of the neural signature of CdF decline, we aim to improve prediction during the preclinical stages of ADs and other dementias. Our approach has important research and translational implications because grEEG protocols are relatively inexpensive and portable, and predicting CdF decline may have real-world benefits. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56726.

Non-literacy biased, culturally fair cognitive detection tool in primary care patients with cognitive concerns: a randomized controlled trial.

Dementia is often undiagnosed in primary care, and even when diagnosed, untreated. The 5-Cog paradigm, a brief, culturally adept, cognitive detection tool paired with a clinical decision support may reduce barriers to improving dementia diagnosis and care. We performed a randomized controlled trial in primary care patients experiencing health disparities (racial/ethnic minorities and socioeconomically disadvantaged). Older adults with cognitive concerns were assigned in a 1:1 ratio to the 5-Cog paradigm or control. Primary outcome was improved dementia care actions defined as any of the following endpoints within 90 days: new mild cognitive impairment syndrome or dementia diagnoses as well as investigations, medications or specialist referrals ordered for cognitive indications. Groups were compared using intention-to-treat principles with multivariable logistic regression. Overall, 1,201 patients (mean age 72.8 years, 72% women and 94% Black, Hispanic or Latino) were enrolled and 599 were assigned to 5-Cog and 602 to the control. The 5-Cog paradigm demonstrated threefold odds of improvement in dementia care actions over control (odds ratio 3.43, 95% confidence interval 2.32-5.07). No serious intervention-related adverse events were reported. The 5-Cog paradigm improved diagnosis and management in patients with cognitive concerns and provides evidence to promote practice change to improve dementia care actions in primary care.ClinicalTrials.gov: NCT03816644 .

Cognitive reserve proxies are associated with age-related cognitive decline - Not age-related gait speed decline.

Cognition and gait share brain substrates in aging and dementia. Cognitive reserve (CR) allows individuals to cope with brain pathology and delay cognitive impairment and dementia. Yet, evidence for that CR is associated with age-related cognitive decline is mixed, and evidence for that CR is associated with age-related gait decline is limited. In 1,079 older (M Age = 75.4 years; 56.0% women) LonGenity study participants without dementia at baseline and up to 12 years of annual follow-up (M follow-up = 3.9 years, SD = 2.5 years), high CR inferred from cognitive (education years), physical (number of blocks walked per day; weekly physical activity days), and social (volunteering/working; living with someone) proxies were associated with slower rates of age-related decline in global cognition - not gait speed decline. Thus, cognitive, physical, and social CR proxies are associated with cognitive decline in older adults without dementia. The multifactorial etiology and earlier decline in gait than cognition may render it less modifiable by CR proxies later in life.

Elevated Blood Homocysteine Increases the Risk of Incident Motoric Cognitive Risk Syndrome: A Two-Cohort Study.

BACKGROUND: Motoric Cognitive Risk (MCR) syndrome, a predementia syndrome characterized by cognitive complaints and slow gait, may have an underlying vascular etiology. Elevated blood levels of homocysteine, a known vascular risk factor, have been linked to physical and cognitive decline in older adults, though the relationship with MCR is unknown. We aimed to identify the association between homocysteine and MCR risk. METHODS: We examined the association between baseline homocysteine levels and incident MCR using Cox proportional hazard models in 1826 community-dwelling older adults (55% women) from 2 cohorts (Einstein Aging Study [EAS] and Quebec Longitudinal Study on Nutrition and Successful Aging [NuAge]). We calculated hazard ratios (HR) with 95% confidence intervals (CI), for each cohort as well as stratified by sex and vascular disease/risk factors. RESULTS: Median follow-up time was 2.2 years in EAS and 3.0 years in NuAge. Individuals with elevated baseline homocysteine levels (>14 µmol/L) had a significantly higher risk of incident MCR compared to those with normal levels in NuAge (HR 1.41, 95% CI: 1.01-1.97, p = .04), after adjusting for covariates. Our exploratory stratified analyses found that these associations were significant only in men with vascular disease/risk factors. CONCLUSIONS: Higher blood homocysteine levels are associated with an increased risk of developing MCR in older adults, particularly in men with vascular disease or vascular risk factors.

Plasma proteomic profile of abdominal obesity in older adults.

OBJECTIVE: This study examines the plasma proteomic profile of abdominal obesity in older adults. METHODS: The association of abdominal obesity (waist circumference [WC]) with 4265 plasma proteins identified using the SomaScan Assay was examined in 969 Ashkenazi Jewish participants (LonGenity cohort), aged 65 years and older (mean [SD] age 75.7 [6.7] years, 55.4% women), using regression models. Pathway analysis, as well as weighted correlation network analysis, was performed. WC was determined from the proteome using elastic net regression. RESULTS: A total of 480 out of 4265 proteins were associated with WC in the linear regression model. Leptin (ß [SE] = 12.363 [0.490]), inhibin ß C chain (INHBC; ß [SE] = 24.324 [1.448]), insulin-like growth factor-binding protein 2 (IGFBP-2; ß [SE] = -12.782 [0.841]), heparan-sulfate 6-O-sulfotransferase 3 (H6ST3; ß [SE] = -39.995 [2.729]), and matrix-remodeling-associated protein 8 (MXRA8; ß [SE] = -27.101 [1.850]) were the top proteins associated with WC. Cell adhesion, extracellular matrix remodeling, and IGF transport pathways were the top enriched pathways associated with WC. WC signature determined from plasma proteins was highly correlated with measured WC (r = 0.80) and was associated with various metabolic and physical traits. CONCLUSIONS: The study unveiled a multifaceted plasma proteomic profile of abdominal obesity in older adults, offering insights into its wide-ranging impact on the proteome. It also elucidated novel proteins, clusters of correlated proteins, and pathways that are intricately associated with abdominal obesity.

Is the Montreal cognitive assessment culturally valid in a diverse geriatric primary care setting? Lessons from the Bronx.

BACKGROUND: Efficacy and validity of the MoCA for cognitive screening in ethnoculturally and linguistically diverse settings is unclear. We sought to examine the utility and discriminative validity of the Spanish and English MoCA versions to identify cognitive impairment among diverse community-dwelling older adults. METHODS: Participants aged ≥65 with cognitive concerns attending outpatient primary care in Bronx, NY, were recruited. MoCA and neuropsychological measures were administered in Spanish or English, and a neuropsychologist determined cognitive status (normal with subjective cognitive concerns [SCC], mild cognitive impairment [MCI], and dementia). One-way ANOVA compared cognitive statuses. ROC analyses identified optimal MoCA cutpoints for discriminating possible cognitive impairment. RESULTS: There were 231 participants, with mean age 73, 72% women, 43% Hispanic; 39% Black/African American; 113 (49%) completed testing in English and 118 (51%) in Spanish. Overall MoCA mean was 17.7 (SD = 4.3). Neuropsychological assessment identified 90 as cognitively normal/SCC, average MoCA 19.9 (SD = 4.1), 133 with MCI, average MoCA 16.6 (SD = 3.7), and 8 with dementia, average MoCA 10.6 (SD = 3.1). Mean English MoCA average was 18.6 (SD = 4.1) versus Spanish 16.7 (SD = 4.3). The published cutpoint ≤23 for MCI yielded a high false-positive rate (79%). ROC analyses identified ≤18.5 as the score to identify MCI or dementia using the English MoCA (65% sensitivity; 77% specificity) and ≤16.5 for the Spanish MoCA (64% sensitivity;73% specificity) in this sample of older adults with cognitive concerns. CONCLUSIONS: Current MoCA cutpoints were inappropriately high in a culturally/linguistically diverse urban setting, leading to a high false-positive rate. Lower Spanish and English MoCA cutpoints may improve diagnostic accuracy for identifying cognitive impairment in this group, highlighting the need for the creation and validation of accurate cognitive screeners for ethnoculturally and linguistically diverse older adults.

Prodromal Motoric Cognitive Risk Syndrome and Everyday Function.

BACKGROUND: Motoric cognitive risk syndrome (MCR), a pre-dementia syndrome characterized by subjective cognitive complaints and slow gait, is associated with disability in instrumental activities of daily living. It is unknown whether these functional limitations occur even before this pre-dementia syndrome is diagnosed. OBJECTIVE: To assess profiles of complex and instrumental activities of daily living in the prodromal stages of MCR. METHODS: We examined functional profiles in 46 older adults (mean age 79 years, 59% women) living in the community with normal cognition at baseline who developed MCR over follow-up ('pre-MCR') with 264 older adults (mean age 75 years, 57% women) who remained cognitively intact over the follow-up period. RESULTS: Pre-MCR individuals had more limitations on complex everyday function at baseline compared to normal controls in multivariable logistic regression models (odds ratio 1.21). Pre-MCR cases at baseline had limitations in handling finances (odds ratio 3.0) and performing hobbies (odds ratio 5.5) as compared to normal controls. Pre-MCR cases had a greater difference in the number of complex functional limitations from baseline to MCR compared to the difference from baseline to final visit for the controls (1.2±3.0 versus 0.5±2.2, p < 0.001). CONCLUSIONS: Limitations in complex everyday tasks arise in the prodromal stages of MCR and can assist in risk prognostication.

Epidemiology of Motoric Cognitive Risk Syndrome in the Kerala Einstein Study: Protocol for a Prospective Cohort Study.

BACKGROUND: The southern India state of Kerala has among the highest proportion of older adults in its population in the country. An increase in chronic age-related diseases such as dementia is expected in the older Kerala population. Identifying older individuals early in the course of cognitive decline offers the best hope of introducing preventive measures early and planning management. However, the epidemiology and pathogenesis of predementia syndromes at the early stages of cognitive decline in older adults are not well established in India. OBJECTIVE: The Kerala Einstein Study (KES) is a community-based cohort study that was established in 2008 and is based in the Kozhikode district in Kerala state. KES aims to establish risk factors and brain substrates of motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by the presence of slow gait and subjective cognitive concerns in individuals without dementia or disability. This protocol describes the study design and procedures for this KES project. METHODS: KES is proposing to enroll a sample of 1000 adults ≥60 years old from urban and rural areas in the Kozhikode district of Kerala state: 200 recruited in the previous phase of KES and 800 new participants to be recruited in this project. MCR is the cognitive phenotype of primary interest. The associations between previously established risk factors for dementia as well as novel risk factors (apathy and traumatic brain injury) and MCR will be examined in KES. Risk factor profiles for MCR will be compared between urban and rural residents as well as with individuals who meet the criteria for mild cognitive impairment (MCI). Cognitive and physical function, medical history and medications, sociodemographic characteristics, lifestyle patterns, and activities of daily living will be evaluated. Participants will also undergo magnetic resonance imaging and electrocardiogram investigations. Longitudinal follow-up is planned in a subset of participants as a prelude to future longitudinal studies. RESULTS: KES (2R01AG039330-07) was funded by the US National Institutes of Health in September 2019 and received approval from the Indian Medical Council of Research to start the study in June 2021. We had recruited 433 new participants from urban and rural sites in Kozhikode as of May 2023: 41.1% (178/433) women, 67.7% (293/433) rural residents, and 13.4% (58/433) MCR cases. Enrollment is actively ongoing at all the KES recruitment sites. CONCLUSIONS: KES will provide new insights into risk factors and brain substrates associated with MCR in India and will help guide future development of regionally specific preventive interventions for dementia. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49933.

Frailty Resilience Score: A Novel Measure of Frailty Resilience Associated With Protection From Frailty and Survival.

Frailty is characterized by increased vulnerability to disability and high risk for mortality in older adults. Identification of factors that contribute to frailty resilience is an important step in the development of effective therapies that protect against frailty. First, a reliable quantification of frailty resilience is needed. We developed a novel measure of frailty resilience, the Frailty Resilience Score (FRS), that integrates frailty genetic risk, age, and sex. Application of FRS to the LonGenity cohort (n = 467, mean age 74.4) demonstrated its validity compared to phenotypic frailty and its utility as a reliable predictor of overall survival. In a multivariable-adjusted analysis, 1-standard deviation increase in FRS predicted a 38% reduction in the hazard of mortality, independent of baseline frailty (p < .001). Additionally, FRS was used to identify a proteomic profile of frailty resilience. FRS was shown to be a reliable measure of frailty resilience that can be applied to biological studies of resilience.

Biological Age Acceleration and Motoric Cognitive Risk Syndrome.

OBJECTIVE: Motoric cognitive risk (MCR) syndrome, a predementia syndrome characterized by slow gait and subjective cognitive concerns, is associated with multiple age-related risk factors. We hypothesized that MCR is associated with biological age acceleration. We examined the associations of biological age acceleration with MCR, and mortality risk in MCR cases. METHODS: Biological age was determined using proteomic and epigenetic clocks in participants aged 65 years and older in the LonGenity study (N = 700, females = 57.9%) and Health and Retirement Study (HRS; N = 1,043, females = 57.1%) cohorts. Age acceleration (AgeAccel) was operationally defined as the residual from regressing predicted biological age (from both clocks separately) on chronological age. Association of AgeAccel with incident MCR in the overall sample as well as with mortality risk in MCR cases was examined using Cox models and reported as hazard ratios (HRs). RESULTS: AgeAccel scores derived from a proteomic clock were associated with prevalent MCR (odds ratio adjusted for age, gender, education years, and chronic illnesses [aOR] = 1.36, 95% confidence interval [CI] = 1.09-1.71) as well as predicted incident MCR (HR = 1.19, 95% CI = 1.00-1.41) in the LonGenity cohort. In HRS, the association of AgeAccel using an epigenetic clock with prevalent MCR was confirmed (aOR = 1.47, 95% CI = 1.16-1.85). Participants with MCR and accelerated aging (positive AgeAccel score) were at the highest risk for mortality in both LonGenity (HR = 3.38, 95% CI = 2.01-5.69) and HRS (HR = 2.47, 95% CI = 1.20-5.10). INTERPRETATION: Accelerated aging predicts risk for MCR, and is associated with higher mortality in MCR patients. ANN NEUROL 2023;93:1187-1197.

Everyday function profiles in prodromal stages of MCI: Prospective cohort study.

INTRODUCTION: The nature and course of limitations in everyday function in the early clinical stages of cognitive decline is not well known. METHODS: We compared complex everyday functional profiles at baseline in 59 community-dwelling older individuals with normal cognitive performance who went on to develop incident mild cognitive impairment (MCI) ("pre-MCI") with 284 older individuals who remained cognitively normal over follow-up. RESULTS: The mean number of limitations on complex everyday function at baseline was 3.1 ± 3.0 in the 59 pre-MCI cases and 2.0 ± 2.4 in the 284 normal controls (P = .003). Pre-MCI cases had limitations in traveling, entertaining, remembering appointments, and hobbies compared to normal controls. A progressive increase in mild limitations on complex everyday function preceded the incidence of MCI (mean change: pre-MCI 1.9 ± 3.6 vs normal controls 0.5 ± 2.7, P < .001). DISCUSSION: Prodromal stages of MCI are associated with progressive mild limitations in complex activities of daily living.

Randomized Controlled Trial of Social Ballroom Dancing and Treadmill Walking: Preliminary Findings on Executive Function and Neuroplasticity From Dementia-at-Risk Older Adults.

This randomized controlled trial (NCT03475316) examined the relative efficacy of 6 months of social ballroom dancing and treadmill walking on a composite executive function score, generated from digit symbol substitution test, flanker interference, and walking while talking tasks. Brain activation during functional magnetic resonance imaging (fMRI) versions of these executive function tasks were secondary outcomes. Twenty-five dementia-at-risk older adults (memory impairment screen score of ≥3 to ≤6 and/or an Alzheimer's disease-8 Dementia Screening Interview of ≥1) were randomized in June 2019 to March 2020-16 completed the intervention before study termination due to the COVID-19 (eight in each group). Composite executive function scores improved post-intervention in both groups, but there was no evidence for between-group differences. Social dancing, however, generated greater improvements on digit symbol substitution test than treadmill walking. No intervention-related differences were observed in brain activation-although less hippocampal atrophy (tertiary) was observed following social dancing than treadmill walking. These preliminary findings are promising but need to be confirmed in future large-scale and sufficiently powered randomized controlled trials.

Age-related changes in gait domains: Results from the LonGenity study.

BACKGROUND: Impairment in gait domains such as pace, rhythm, and variability are associated with falls, cognitive decline, and dementia. However, the longitudinal changes in these gait domains are poorly understood. The aim of this study was to examine age-related changes in gait domains overall and in those with cognitive impairment and mobility disability. METHODS: Participants were from the LonGenity study (n = 797; M Age=75.1 SD 6.5 years; 58.2% female) and were followed up to 12 years (Median=3.3; IQR: 1.1; 6.3). Gait speed and absolute values of step length, step time, cadence and, variability (standard deviation) of step length and step time during usual pace walking were assessed. Principal components analysis was used to obtain weighted combinations of three gait domains: pace (velocity, step length), variability (step length variability, step time variability) and rhythm (step time). Linear mixed effect models were used to examine age-related changes in gait domains overall, and in those with cognitive impairment and mobility disability at baseline. RESULTS: Pace declined, and rhythm increased (worsened) in an accelerating non-linear fashion. Variability gradually increased with age. Those with cognitive impairment had faster rates of change in pace and rhythm. Those with mobility disability had faster increases in rhythm. CONCLUSIONS: Age-related changes in gait domains are not uniform. Individuals with cognitive and mobility impairments are particularly vulnerable to accelerated change in pace and or rhythm.

Longitudinal Associations Between Falls and Risk of Gait Decline: Results From the Central Control of Mobility and Aging Study.

OBJECTIVE: To examine whether falls are associated with longitudinal changes in different gait domains and onset of clinical gait abnormalities. DESIGN: Longitudinal study. SETTING: General community. PARTICIPANTS: Ambulatory older adults free of dementia (N=428; mean age, 77.8±6.4 years). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Gait was assessed with a computerized walkway. Pace, rhythm, and variability (outcome measures) were derived from individual gait measures, using principal component analysis. Clinical gait abnormalities (neurologic, nonneurologic, mixed) were visually assessed by clinicians. Linear mixed-effects models were used to examine the associations between falls (the exposure variable coded as none, single, and multiple) and changes in gait domains. Multinomial logistic regression was used to examine associations between falls and the onset of clinical gait abnormalities. Models were adjusted for sex, education, age, body mass index, number of comorbidities, gait speed at the first follow-up, and time between the last fall and the first follow-up gait assessment. RESULTS: Pace declined while rhythm and variability increased at a faster rate (P<.05) among 32 participants with multiple falls in the first year of follow-up compared with 299 participants with no falls. Risk for clinical gait abnormalities between those with no falls, a single fall, or multiple falls was not different. CONCLUSIONS: Multiple falls predict future gait decline in multiple domains in aging. Interventions to prevent gait decline after multiple falls should be investigated.

Inflammatory biomarkers and motoric cognitive risk syndrome: Multicohort survey.

Background: Inflammation may play a role in Motoric Cognitive Risk (MCR) syndrome, a pre-dementia syndrome comprised of slow gait and cognitive complaints. Our objective was to examine associations of inflammatory biomarkers with MCR. Methods: We examined association of interleukin-6 (IL-6) and C-reactive protein (CRP) with prevalent MCR using logistic regression in 3,101 older adults (52% female) from five cohorts (National Center for Geriatrics & Gerontology Study of Geriatric Syndromes [NCGG-SGS], Central Control of Mobility in Aging [CCMA], Tasmanian Study of Cognition and Gait [TASCOG], LonGenity, and Einstein Aging Study [EAS]). Associations were reported as odds ratios adjusted for sex, age, education, depressive symptoms, body mass index, and vascular diseases (aOR) with 95% confidence intervals (CI). Meta-analysis and analyses stratified by vascular disease were also done. Results: Although associations between higher (worse) CRP and IL-6 tertiles and MCR were only seen in three out of the five cohorts (EAS, TASCOG, and LonGenity), when a pooled meta-analysis was performed, a robust association was demonstrated. In meta-analysis, highest tertiles of IL-6 (aOR 1.57, 95%CI 1.01- 2.44) and CRP (aOR 1.65, 95%CI 1.09-2.48) was associated with MCR versus lowest tertiles in the pooled sample. Higher CRP was associated with MCR among those with vascular disease in TASCOG and LonGenity cohorts, and among those without vascular disease in EAS. Conclusions: IL-6 and CRP levels are associated with MCR in older adults, and this association varies by presence of vascular disease.

Olfactory Dysfunction and Incidence of Motoric Cognitive Risk Syndrome: A Prospective Clinical-Pathologic Study.

BACKGROUND AND OBJECTIVES: To examine associations between olfactory dysfunction, Alzheimer's disease (AD) pathology, and motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait that is associated with risk for AD and other dementias. METHODS: We conducted a retrospective analysis of a prospective cohort study to examine if baseline olfactory function was associated with risk of incident MCR in 1,119 adults aged 60 and older (75.1% female). The association between performance on the Brief Smell Identification Test (BSIT) and incident MCR risk was computed using Cox models and reported as Hazard ratio (HR) with 95% confidence intervals (CI) adjusted for demographic, comorbidity, and cognitive factors. Furthermore, we assessed the relationship between postmortem AD pathology as well as non-AD pathology and olfactory function at the time of MCR diagnosis using linear regression models adjusted for sex, education, age at death, and time from diagnosis to death. RESULTS: There were 544 (48.6%) incident cases of MCR over a median follow-up of 3.94 years. Lower BSIT scores (poor olfaction) at baseline were associated with an increased risk of incident MCR (HR for a 1-point increase in BSIT score, 0.92; 95% CI, 0.88-0.96) in fully adjusted models. Those with hyposmia (scores of ≤8 on the BSIT) at baseline (26.6%) were at increased risk of MCR (HR, 1.44; 95% CI, 1.19-1.74) compared to those with normal olfactory function. A composite measure of global AD pathology as well as presence of Lewy body pathology were both inversely and independently associated with BSIT scores at the time of incident MCR diagnosis (n=118). τ tangle density, a specific component of AD pathology, was inversely associated with olfactory function and the correlation remained after controlling for mild cognitive impairment syndrome as well as presence of Lewy body pathology. DISCUSSION: The results provide evidence that olfactory dysfunction precedes MCR incidence and is related to Alzheimer pathology; providing a clinical approach to risk stratify as well as subtype MCR.

Increased Social Support Reduces the Incidence of Motoric Cognitive Risk Syndrome.

Background and Objectives: The motoric cognitive risk syndrome (MCR) is a predementia syndrome characterized by slow gait and cognitive complaint. The relationship between MCR and social support-a potentially modifiable risk factor of dementia-is currently unknown. The current study aimed to determine whether MCR incidence varies as a function of social support in aging. Research Design and Methods: We examined MCR incidence in 506 community-dwelling older adults (M Age 76.59; 57.3% female) without MCR or dementia at baseline. We quantified perceived levels of social support with the Medical Outcomes Study Social Support Survey, incorporating four different categories of support: (a) emotional/informational support, (b) tangible support, (c) affectionate support, and (d) positive social interactions. We used Cox regression analyses, adjusted for age, sex, race/ethnicity, education, marital status, comorbidities, and global cognition, to estimate hazard ratios (aHR) with 95% confidence intervals (CIs). Results: Over a median follow-up time of 2.5 years (range = 1-7 years), 38 participants (9.8%) developed MCR. Increased tangible support decreased the risk of MCR by 30% (aHR: 0.70, 95% CI: 0.53-0.92, p = .011). Increased overall social support decreased the risk of MCR by 33% (aHR: 0.67, 95% CI: 0.46-0.98, p = .038). Other subcategories of social support were not associated with a decreased risk of MCR (p > .05). Discussion and Implications: Higher levels of tangible social support, as well as overall social support, were associated with reduced risk for MCR in older adults. Increasing social support may be a promising avenue of intervention for reducing the risk of MCR, dementia, and other forms of cognitive decline.

Mediation Analyses of the Role of Apathy on Motoric Cognitive Outcomes.

Recent literature indicates that apathy is associated with poor cognitive and functional outcomes in older adults, including motoric cognitive risk syndrome (MCR), a predementia syndrome. However, the underlying biological pathway is unknown. The objectives of this study were to (1) examine the cross-sectional associations between inflammatory cytokines (Interleukin 6 (IL-6) and C-Reactive Protein (CRP)) and apathy and (2) explore the direct and indirect relationships of apathy and motoric cognitive outcomes as it relates to important cognitive risk factors. N = 347 older adults (≥65 years old) enrolled in the Central Control of Mobility in Aging Study (CCMA). Linear and logic regression models showed that IL-6, but not CRP was significantly associated with apathy adjusted for age, gender, and years of education (ß = 0.037, 95% CI: 0.002-0.072, p = 0.04). Apathy was associated with a slower gait velocity (ß = -14.45, 95% CI: -24.89-4.01, p = 0.01). Mediation analyses demonstrated that IL-6 modestly mediates the relationship between apathy and gait velocity, while apathy mediated the relationships between dysphoria and multimorbidity and gait velocity. Overall, our findings indicate that apathy may be an early predictor of motoric cognitive decline. Inflammation plays a modest role, but the underlying biology of apathy warrants further investigation.

Validation of a "subjective motoric cognitive risk syndrome" screening tool for motoric cognitive risk syndrome-A prospective cohort study.

BACKGROUND AND PURPOSE: Motoric cognitive risk syndrome (MCR) is a gait-based pre-dementia syndrome associated with risk of dementia. Ascertaining subjective cognitive and motoric complaints may facilitate early and remote identification of individuals with MCR as they are reported to precede and predict objective cognitive and motoric impairments in aging. METHODS: The validity of five subjective motoric complaint (SMC) questions and 10 subjective cognitive complaint (SCC) questions was examined for discriminating MCR in 538 non-demented community-dwelling adults. Backward logistic regression was used to identify questions to develop a weighted score to define subjective MCR (MCR-S). Receiver operating characteristic analysis was applied to determine the discriminative ability of MCR-S for the objective MCR (MCR-O) definition based on SCCs and objectively measured gait. Cox proportional hazard models adjusted for potential confounders were used to examine the predictive validity of MCR-S for incident dementia. RESULTS: Five subjective complaint questions (three SCC and two SMC) were associated with MCR-O. They were combined to define an MCR-S score (range 0-7) which yielded an area under the curve of 0.89 for discriminating MCR-O from receiver operating characteristic analysis. An optimal cut-score of 2 on the MCR-S score was determined to have good sensitivity (84%) and specificity (82%) for MCR-O. Over a median follow-up of 2.5 years, 29 participants developed dementia. Both MCR-S (adjusted hazard ratio 2.39) and MCR-O at baseline (adjusted hazard ratio 3.16) predicted risk of incident dementia. CONCLUSIONS: Subjective MCR had high concordance with MCR-O and can provide a remote screening assessment for MCR-O, which can identify those at high risk for dementia.

The 5-Cog paradigm to improve detection of cognitive impairment and dementia: clinical trial protocol.

Cognitive impairment related to dementia is under-diagnosed in primary care despite availability of numerous cognitive assessment tools; under-diagnosis is more prevalent for members of racial and ethnic minority groups. Clinical decision-support systems may improve rates of primary care providers responding to positive cognitive assessments with appropriate follow-up. The 5-Cog study is a randomized controlled trial in 1200 predominantly Black and Hispanic older adults from an urban underserved community who are presenting to primary care with cognitive concerns. The study will validate a novel 5-minute cognitive assessment coupled with an electronic medical record-embedded decision tree to overcome the barriers of current cognitive assessment paradigms in primary care and facilitate improved dementia care.

Dementia is common, though under-recognized, in older adults (OAs). Primary care providers (PCPs) miss opportunities to help patients and their families manage the disease because of failure to, or delay to, make an appropriate diagnosis. Black and Hispanic OAs are more likely than White OAs to experience delayed diagnosis. Most available memory tests are too long for practical use by PCPs, and are ill suited to patients of diverse language, cultural and educational backgrounds. Studies have shown that even when patients test positive for dementia in primary care, PCPs often do not take follow-up action. Our improved memory test, the 5-Cog, is brief (5 min), not biased by language issues (uses pictures and symbols instead of words), and simple (doesn't require expensive technology and complex staff training). The 5-Cog is paired with a clinical decision support tool, providing tailored recommendations directly into the patient's medical record, and making it easier for PCPs to take appropriate action. This study will evaluate whether the 5-Cog paradigm results in improved dementia care.