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.

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.

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.

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.

Longitudinal associations between falls and future risk of cognitive decline, the Motoric Cognitive Risk syndrome and dementia: the Einstein Ageing Study.

BACKGROUND: falls share risk factors with cognitive decline but whether falls predict cognitive decline, pre-dementia syndromes and dementia is poorly understood. OBJECTIVES: this study aimed to examine if falls are associated with cognitive decline in specific domains and the risk of Motoric Cognitive Risk (MCR) syndrome and dementia. DESIGN: cross-sectional study. METHODS: in older people (age 80.6 ± 5.3 years) free of dementia at baseline, the number of falls (none, one or multiple) during the year before enrolment and the first year of follow-up (exposure) were recorded. Decline in specific cognitive functions (global cognition, episodic verbal memory, verbal fluency, working memory, response inhibition and processing speed-attention), incident MCR and incident dementia were outcome measures. Linear mixed effects models were used to examine the associations between falls and cognitive decline, adjusting for confounders. Cox proportional hazards models were used to determine if falls predicted risk of incident MCR or dementia. RESULTS: of 522 eligible participants, 140 had a single fall and 70 had multiple falls. Multiple falls were associated with a greater decline in global cognition, episodic memory, verbal fluency and processing speed-attention compared to those with no falls (P < 0.05). Over a median follow-up of 1.0 years 36 participants developed MCR and 43 participants developed dementia. Those with multiple falls had a two-fold increased risk of MCR compared to those with no falls, but no increased risk of developing dementia. CONCLUSIONS: multiple falls may be an important marker to identify older people at greater risk of future cognitive decline and incident MCR.

Risk factors for the progression of motoric cognitive risk syndrome to dementia: Retrospective cohort analysis of two populations.

BACKGROUND AND PURPOSE: Motoric cognitive risk syndrome (MCR) is a predementia syndrome characterized by cognitive complaints and slow gait. MCR is associated with increased risk of cognitive decline and incident dementia. Predictors of transition to dementia in MCR patients are still obscure. METHODS: We examined clinical, biological and lifestyle parameters related to conversion to dementia using Cox models in 439 older adults with prevalent MCR (mean age 79.87 ± 8.13 years, 70% women) from two cohorts, 268 from the Chicago-based Rush Memory and Aging project (MAP) and 171 from the Religious Orders Study (ROS), which enrolled religious clergy across the United States. RESULTS: In the pooled sample, 439 (13.2%) had prevalent MCR (268 MAP and 171 ROS). There were 140 (31.9%) incident dementia cases over a median follow up of 4.0 years. Age predicted conversion from MCR to dementia in both cohorts. Male gender was a risk factor only in ROS. In the pooled data, only higher depressive symptoms were associated with higher risk of conversion to dementia (adjusted hazard ratio [aHR] 1.13, 95% CI 1.03-1.24). Lower cognitive activity participation (aHR 0.59, 95% CI 0.44-0.79) and apolipoprotein E ε4 allele (aHR 2.57, 95% CI 1.48-4.45) predicted conversion to dementia in MAP. CONCLUSIONS: Depressive symptoms and other cohort-specific risk factors were identified as predictors of transition to dementia in individuals with MCR. These findings suggest common pathological mechanisms underlying mood, gait and cognitive declines in aging, which could help develop preventive strategies.

Gender-stratified analyses reveal longitudinal associations between social support and cognitive decline in older men.

Objectives: Research has extensively examined the relationship between social support and health outcomes in older adults. Little is known, however, about the longitudinal associations between distinct dimensions of perceived social support and incident cognitive decline. The current longitudinal study examined whether dimensions of perceived social support were associated with increased risk of cognitive decline, and if the relationship differed by gender. Methods: 493 community-residing non-demented older adults were assessed for baseline social support via the Medical Outcomes Study-Social Support Survey (MOS-SSS). Incident cognitive impairment was determined using a 1 standard deviation below age and education adjusted total score on the Repeatable Battery for the Assessment of Neuropsychological Status Cox proportional-hazard models were used to analyze incident risk of cognitive impairment. Results: Higher perceived support, overall and in specific domains, at baseline was associated with increased risk of incident cognitive impairment. Further gender-stratified analyses revealed that higher perceived support at baseline was associated with increased risk of incident cognitive impairment only among males. Conclusion: Contrary to previous research, results from this longitudinal study suggest that perceived support might be an important risk factor for cognitive decline, notably in males, and should be integrated into multifactorial risk assessment and intervention procedures.

Motoric cognitive risk syndrome and predictors of transition to dementia: A multicenter study.

INTRODUCTION: To report clinical predictors of transition to dementia in motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait. METHODS: We examined if cognitive or motoric impairments predicted transition to dementia in 610 older adults with MCR from three cohorts. Association of cognitive (logical memory, clinical dementia rating, cognitive complaint severity, and Mini-Mental State Examination) and motoric factors (gait velocity) with dementia risk was computed using Cox models. RESULTS: There were 156 incident dementias (134 Alzheimer's disease). In the pooled sample, logical memory (adjusted hazard ratio [aHR] 0.91), cognitive complaint severity (aHR 1.53), and Mini-Mental State Examination (aHR 0.75) predicted transition of MCR to dementia. Clinical dementia rating score ≥0.5 predicted dementia (aHR 3.18) in one cohort. Gait velocity did not predict dementia. DISCUSSION: While MCR is a motoric-based predementia syndrome, severity of cognitive but not motoric impairments predicts conversion to dementia.

Walking While Talking and Risk of Incident Dementia.

INTRODUCTION: Walking while talking (WWT) is a performance-based test of divided attention that examines cognitive-motor interactions. The purpose of this study is to examine the predictive validity of WWT for dementia and dementia subtypes. METHODS: We prospectively studied the associations of WWT performance at baseline with risk of developing incident dementia in 1,156 older adults (mean age: 78.28 ± 5.27 years, 60.7% female) enrolled in the Einstein Aging Study using Cox proportional hazard models. Associations were reported as hazard ratio (HR) with 95% confidence intervals (CI). RESULTS: Over a median follow-up of 1.90 years (interquartile range: 4.70 years), 85 participants developed incident dementia (53 Alzheimer dementia [AD] and 26 vascular dementia [VaD]). Three gait domains were derived using principal component analysis. Only variability, which loaded heavily for swing time standard deviation (SD) and step time SD, was associated with an increased risk of incident dementia per 1 point increase (HR: 1.24, 95% CI: 1.02-1.54) and VaD (HR: 1.50, 95% CI: 1.06-2.12) after adjusting for demographics, disease burden, mental status, and normal walking velocity. Among eight individual gait variables, only swing time variability SD was associated with increased risk for both incident dementia (HR: 1.35, 95% CI: 1.03-1.77) and VaD (HR: 1.78, 95% CI: 1.12-2.83). Variability and swing time SD were not significantly associated with risk of incident AD. CONCLUSIONS: Complex walking as assessed by the WWT task is a simple and pragmatic tool for assessing risk of developing dementia, especially VaD, in older adults.

Spatial navigation and risk of cognitive impairment: A prospective cohort study.

INTRODUCTION: Spatial navigation deficits are reported in dementia, but their temporal relationship to cognitive decline is not established. METHODS: This is a prospective cohort study in 442 nondemented adults (mean age 79.9 years). Spatial navigation measured with the Floor Maze Test and reported as immediate maze time (IMT) and delayed maze time (DMT). Predementia syndromes, mild cognitive impairment syndrome (MCI) and motoric cognitive risk syndrome (MCR), were primary outcomes. RESULTS: Over a mean follow-up of 16.5 ± 13.7 months, 41 participants developed MCI and 30 participants developed MCR. In Cox models adjusted for age, sex, education, cognitive status, comorbid illnesses, and maze errors, a 10-second increment on IMT predicted incident MCI (adjusted hazard ratio [aHR]: 1.25; 95% confidence interval [CI]: 1.06-1.48) and MCR (aHR: 1.53; 95% CI: 1.23-1.90). DMT predicted MCR but not MCI. DISCUSSION: Spatial navigation performance predicted predementia syndromes in aging and implicates navigational impairments as an early feature in dementias.

Motoric cognitive risk syndrome and risk of mortality in older adults.

INTRODUCTION: Cognitive impairment is associated with increased mortality. We examined the association between motoric cognitive risk (MCR) syndrome, a predementia syndrome characterized by slow gait and cognitive complaints, and survival. METHODS: A total of 11,867 nondemented participants aged >65 years from three established cohort studies in the United States and Europe were screened for MCR. Mortality risk of MCR was assessed with Cox and logistic regression models. RESULTS: At baseline, 836 (7.0%) participants had MCR. Over a median follow-up of 28 months, 1603 participants died (758 in first 2 years). MCR was associated with increased mortality overall (adjusted hazard ratio, 1.69; 95% confidence interval [CI], 1.46-1.96) and 2-year mortality (adjusted odds ratio, 1.89; 95% CI, 1.50-2.38). The association remained after accounting for established mortality risk factors as well as baseline gait speed and memory performance. DISCUSSION: MCR is associated with increased mortality. Older adults should be screened for MCR to identify at-risk individuals for dementia and death.

Walking while talking and falls in aging.

BACKGROUND: While divided attention tasks are recognized as predictors of falls in older adults, a comprehensive examination of this association is lacking. OBJECTIVE: We examined the validity of a 'walking while talking' (WWT) task for predicting falls. METHODS: We studied the associations of 8 selected gait markers measured during WWT (individually as well as domains derived by factor analysis) with incident falls in 646 adults (mean age 79.9 years; 61% women) enrolled in an aging study who received quantitative gait assessments. Cox regressions adjusted for multiple potential confounders and normal-pace walking were used to examine the associations. RESULTS: Over a mean follow-up of 2.6 years, 337 participants (52%) fell. Step length was the only individual WWT parameter that predicted falls [hazard ratio (HR) 0.98; p = 0.034]. Factor analysis identified 3 gait domains, of which only the pace factor predicted falls (HR 1.31; p = 0.002). Results remained robust after adjusting for multiple potential confounders and accounting for normal-pace walking. CONCLUSIONS: WWT performance was a significant predictor of falls. Gait domains in WWT should be further studied to improve current fall risk assessments and to develop new interventions.

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.

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.

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.

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.

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 .

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.