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.

Hypothalamic MRI-derived microstructure is associated with neurocognitive aging in humans.

The hypothalamus regulates homeostasis across the lifespan and is emerging as a regulator of aging. In murine models, aging-related changes in the hypothalamus, including microinflammation and gliosis, promote accelerated neurocognitive decline. We investigated relationships between hypothalamic microstructure and features of neurocognitive aging, including cortical thickness and cognition, in a cohort of community-dwelling older adults (age range 65-97 years, n=124). Hypothalamic microstructure was evaluated with two magnetic resonance imaging diffusion metrics: mean diffusivity (MD) and fractional anisotropy (FA), using a novel image processing pipeline. Hypothalamic MD was cross-sectionally positively associated with age and it was negatively associated with cortical thickness. Hypothalamic FA, independent of cortical thickness, was cross-sectionally positively associated with neurocognitive scores. An exploratory analysis of longitudinal neurocognitive performance suggested that lower hypothalamic FA may predict cognitive decline. No associations between hypothalamic MD, age, and cortical thickness were identified in a younger control cohort (age range 18-63 years, n=99). To our knowledge, this is the first study to demonstrate that hypothalamic microstructure is associated with features of neurocognitive aging in humans.

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.

Loneliness predicts decreased physical activity in widowed but not married or unmarried individuals.

Background: Physical activity is associated with improved health and function in older adults, yet most older adults are sedentary. Loneliness is associated with decreased physical activity at the cross-section, but longitudinal studies are scarce. We examined longitudinal associations between loneliness and physical activity-and whether they were modified by marital status and network size (the number of children, relatives, and friends a person interacts with at least once a month). Methods: We analyzed data from 1,931 older adults without dementia at baseline from the Rush Memory and Aging Project with a mean follow-up of 4.8 years (mean age 79.6 ± 7.7, 74.9% women). Loneliness was assessed using the de Jong Gierveld Loneliness Scale. Physical activity was assessed as the frequency with which participants engaged in five categories of activities (e.g., walking, gardening, calisthenics, bicycling, and swimming). Linear mixed effects models examined associations between baseline loneliness and change in physical activity over time after adjusting for demographics, depressive symptoms, global cognition, disability, network size, marital status, social support, and social and cognitive activities. We assessed for effect modification by marital status and network size. Results: Associations between loneliness and physical activity differed by marital status. In widowed individuals, baseline loneliness was associated with a 0.06 h/week greater decrease in physical activity per year compared to those who were not lonely (p = 0.005, CI -0.1, 0.02)-which equaled a 150% decrease in physical activity per year. Loneliness did not predict a statistically significant decrease in physical activity in married or unmarried individuals. Discussion: Loneliness is associated with decreased physical activity in widowed older adults and should be considered in the design of interventions to prevent or slow the decline in physical activity and promote healthy aging.

Longitudinal Associations of Social Support and Gait Speed Decline in Aging.

BACKGROUND: Social support predicts functional and cognitive decline in aging. Yet, the associations between social support and gait speed decline-a functional vital sign-are not well understood. This study examined associations between social support and gait speed decline in aging. METHODS: Social support and gait data from 542 older adults without dementia were examined (mean age 76.1 ±â€…6.5 years). Baseline emotional support, tangible support, affectionate support, positive social interactions, and overall support from the Medical Outcomes Study Social Support Survey were the predictors of interest. Annual change in simple (normal pace walking) and complex (walking while reciting alternate letters of the alphabet) gait speed (cm/s) were the outcomes of interest. Linear mixed effects models examined associations between social support and gait speed decline, after adjusting for gender, race, depressive symptoms, overall cognition, and comorbidities. RESULTS: The mean annual change in gait speed was 1.8 cm/s during simple walking and 1.13 cm/s during complex walking. Tangible support was the only category of social support that predicted decline in simple and complex gait speed over a median follow-up of 3 years. The annual decline in gait speed was 0.51 cm/s (p = .008, 95% confidence intervals [CI] 0.13, 0.89) and 0.58 cm/s (p = .007, CI 0.16, 1.0) greater among those with low tangible support than in those with high tangible support during simple and complex walking, respectively. CONCLUSIONS: Tangible support is a potentially modifiable risk factor for gait speed decline. Further study is needed to examine mechanisms behind the observed associations and the potential for intervention.

Difference-Making Pathways to Frailty Through Social Factors: A Configurational Analysis.

BACKGROUND AND OBJECTIVES: Social disconnection is highly prevalent in older adults and is associated with frailty. It is unclear which aspects of social disconnection are most associated with frailty, which ones are difference-making, and which combination of social factors are directly linked to frailty. RESEARCH DESIGN AND METHODS: We conducted a secondary coincidence analysis (CNA) of 1,071 older adults from the Rush Memory and Aging Project (mean age 79.3 ± 7.1; 75.8% female) to identify combinations of social factors that are difference-making for frailty. We included 7 demographic (e.g., age, sex, socioeconomic status) and structural (e.g., social network), functional (e.g., social support, social activity), and quality (e.g., loneliness) aspects of social connection. An established cut score of 0.2 on a frailty index was used to define frailty as the outcome. RESULTS: CNA produced 46 solution models for the presence of frailty in the data set. The top-scoring model was underfit, leaving a final complex solution path for frailty with the highest fit-robustness score that met the fit parameter cutoffs. We found that the combination of loneliness, low social activity, and older age was present 82% of the time when frailty was present. DISCUSSION AND IMPLICATIONS: The combination of loneliness, social activity, and old age is difference-making for frailty, and supports the inclusion of social factors in frailty prevention and intervention. Further research is needed in diverse data sets to better understand the interrelationships between the 3 aspects of social connection and frailty.

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.

Loneliness and Functional Decline in Aging: A Systematic Review.

Loneliness is prevalent in adults aged ≥65 years in the United States and is associated with functional decline. The purpose of the current review was to synthesize evidence on the relationship between loneliness and functional decline using Roy's Adaptation Model as a theoretical framework. A comprehensive review of PubMed, Medline, and Embase databases was performed. Inclusion criteria were samples including adults primarily aged >60 years, peer-reviewed, published in the English language, and included a measure for loneliness and function. A total of 47 studies were analyzed. Most studies examined correlates, risk factors, and predictors of loneliness, rather than the relationship between loneliness and function. Evidence suggests there is bidirectionality in the relationship between loneliness and functional decline. Loneliness is associated with functional decline in aging via multiple possible pathways. Further studies are needed to determine causality and biological mechanisms underlying the relationship. [Research in Gerontological Nursing, 16(4), 202-212.].

Visual-somatosensory integration (VSI) as a novel marker of Alzheimer's disease: A comprehensive overview of the VSI study.

Identification of novel, non-invasive, non-cognitive based markers of Alzheimer's disease (AD) and related dementias are a global priority. Growing evidence suggests that Alzheimer's pathology manifests in sensory association areas well before appearing in neural regions involved in higher-order cognitive functions, such as memory. Previous investigations have not comprehensively examined the interplay of sensory, cognitive, and motor dysfunction with relation to AD progression. The ability to successfully integrate multisensory information across multiple sensory modalities is a vital aspect of everyday functioning and mobility. Our research suggests that multisensory integration, specifically visual-somatosensory integration (VSI), could be used as a novel marker for preclinical AD given previously reported associations with important motor (balance, gait, and falls) and cognitive (attention) outcomes in aging. While the adverse effect of dementia and cognitive impairment on the relationship between multisensory functioning and motor outcomes has been highlighted, the underlying functional and neuroanatomical networks are still unknown. In what follows we detail the protocol for our study, named The VSI Study, which is strategically designed to determine whether preclinical AD is associated with neural disruptions in subcortical and cortical areas that concurrently modulate multisensory, cognitive, and motor functions resulting in mobility decline. In this longitudinal observational study, a total of 208 community-dwelling older adults with and without preclinical AD will be recruited and monitored yearly. Our experimental design affords assessment of multisensory integration as a new behavioral marker for preclinical AD; identification of functional neural networks involved in the intersection of sensory, motor, and cognitive functioning; and determination of the impact of early AD on future mobility declines, including incident falls. Results of The VSI Study will guide future development of innovative multisensory-based interventions aimed at preventing disability and optimizing independence in pathological aging.

Gait in cerebral small vessel disease, pre-dementia, and dementia: A systematic review.

BACKGROUND: The interrelationships between gait, cerebral small vessel disease (CSVD), and cognitive impairments in aging are not well-understood-despite their common co-occurrence. OBJECTIVE: To systematically review studies of gait impairment in CSVD, pre-dementia, and dementia, and to identify key gaps for future research and novel pathways toward intervention. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided search strategy was implemented in PubMed to identify relevant studies. Potential articles (n = 263) published prior to 1 December 2021 were screened by two reviewers. Studies with sample sizes >20 and including some adults over > 65 years (n = 202) were included. RESULTS: The key findings were that (1) adverse gait and cognitive outcomes were associated with several (rather than select) CSVD pathologies distributed across the brain, and (2) poor gait and CSVD pathologies were more strongly associated with dementia with a vascular, rather than an Alzheimer's disease-related, cause. DISCUSSION: A better understanding of the interrelationships between gait performance in CSVD, pre-dementia, and dementia requires studies examining (1) comprehensive patterns in the clinical manifestations of CSVD, (2) racially/ethnically diverse samples, (3) samples followed for extended periods of time or across the adult life span, (4) non-traditional CSVD neuroimaging markers (e.g. resting-state functional magnetic resonance imaging (fMRI)), and (5) continuous (e.g. wearable sensors) and complex (e.g. dual-task) walking performance.

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.

Neural signature of mobility-related everyday function in older adults at-risk of cognitive impairment.

Assessment of everyday activities is central to the diagnosis of dementia. Yet, little is known about brain processes associated with everyday functional limitations, particularly during early stages of cognitive decline. Twenty-six older adults (mean = 74.9 y) were stratified by risk using the Montreal Cognitive Assessment battery (MoCA, range: 0- 30) to classify individuals as higher (22-26) and lower risk (27+) of cognitive impairment. We investigated everyday function using a gait task designed to destabilize posture and applied Mobile Brain/Body Imaging. We predicted that participants would increase step width to gain stability, yet the underlying neural signatures would be different for lower versus higher risk individuals. Step width and fronto-parietal activation increased during visually perturbed input. Frontomedial theta increased in higher risk individuals during perturbed and unperturbed inputs. Left sensorimotor beta decreased in lower risk individuals during visually perturbed input. Modulations in theta and beta power were associated with MoCA scores. Our findings suggest that older adults at-risk of cognitive impairment can be characterized by a unique neural signature of everyday function.

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.

Brain patterns of pace - but not rhythm - are associated with vascular disease in older adults.

Background: Distinct domains of gait such as pace and rhythm are linked to an increased risk for cognitive decline, falls, and dementia in aging. The brain substrates supporting these domains and underlying diseases, however, remain relatively unknown. The current study aimed to identify patterns of gray matter volume (GMV) associated with pace and rhythm, and whether these patterns vary as a function of vascular and non-vascular comorbidities. Methods: A cross-sectional sample of 297 older adults (M Age = 72.5 years ± 7.2 years, 43% women) without dementia was drawn from the Tasmanian Study of Cognition and Gait (TASCOG). Factor analyses were used to reduce eight quantitative gait variables into two domains. The "pace" domain was primarily composed of gait speed, stride length, and double support time. The "rhythm" domain was composed of swing time, stance time, and cadence. Multivariate covariance-based analyses adjusted for age, sex, education, total intracranial volume, and presence of mild cognitive impairment identified gray matter volume (GMV) patterns associated with pace and rhythm, as well as participant-specific expression (or factor) scores for each pattern. Results: Pace was positively associated with GMV in the right superior temporal sulcus, bilateral supplementary motor areas (SMA), and bilateral cerebellar regions. Rhythm was positively associated with GMV in bilateral SMA, prefrontal, cingulate, and paracingulate cortices. The GMV pattern associated with pace was less expressed in participants with any vascular disease; this association was also found independently with hypertension, diabetes, and myocardial infarction. Conclusion: Both pace and rhythm domains of gait were associated with the volume of brain structures that have been linked to controlled and automatic aspects of gait control, as well as with structures involved in multisensory integration. Only the brain structures associated with pace, however, were associated with vascular disease.

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.

Risk factors for decline in gait speed during walking while talking in older adults.

BACKGROUND & AIMS: Slow gait speed during Walking While Talking (walking while reciting alternate letters of the alphabet; WWT) is associated with an increased risk of developing dementia and falls. The aim of this study was to examine longitudinal changes in WWT-speed and to identify risk factors that may modify the rate of change in WWT-speed. METHODS: A total of 431 older participants (55.7% female; M Age=76.8 ± 6.4 years; mean follow up 2.1 ± 1.8 years) enrolled in the Central Control of Mobility in Aging study were examined. WWT-speed (cm/s) was measured with a computerized walkway. The following baseline measures were examined as risk factors: demographics [age, sex, education], medical illnesses [hypertension, diabetes, cardiac arrhythmias, history of stroke, Parkinson's disease, kidney disease, arthritis], cognitive functions [global cognition, executive function, processing speed], physical and sensory functions [unipedal stance time, gait speed during single task walking, visual acuity], psychological variables [depression, anxiety] and falls. Linear mixed effect models were used to examine 1) change in WWT-speed over time, and 2) risk factors associated with change in WWT-speed over time. RESULTS: WWT-speed declined in an accelerating non-linear fashion over time after adjusting for baseline age, sex and education. The rate of decline in WWT-speed was modified by older age (b -0.16 95%CI -0.22, -0.09), poorer balance (b -1.73 95%CI -2.57, -0.90), and faster gait speed during single task walking (b -0.06 95%CI -0.08, -0.04). SIGNIFICANCE: This study identified fixed and modifiable risk factors of faster decline in WWT-speed over time in community-residing older adults.

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.

Relative Trajectories of Gait and Cognitive Decline in Aging.

BACKGROUND: Gait and cognition decline with advancing age, and presage the onset of dementia. Yet, the relative trajectories of gait and cognitive decline in aging are poorly understood-particularly among those with the motoric cognitive risk (MCR) syndrome. This study compared changes in simple and complex gait performance and cognition, as a function of age and MCR. METHODS: We examined gait and cognitive functions of 1 095 LonGenity study participants (mean age = 75.4 ± 6.7 years) with up to 12 years of annual follow-up. Participants were of Ashkenazi Jewish descent, free of dementia, ambulatory, and had a 12.2% MCR prevalence at baseline. Gait speed was measured at usual pace walking (single-task walking, STW-speed) and walking while talking (WWT-speed). Eleven neuropsychological test scores were examined separately, and as a global cognition composite. Linear mixed-effects models adjusted for baseline sex, education, parental longevity, cognitive impairment, and global health were used to estimate changes in gait and cognition, as a function of age and MCR. RESULTS: STW-speed, WWT-speed, and cognitive tests performance declined in a nonlinear (accelerating) fashion with age. STW-speed declined faster than WWT-speed and cognitive test scores. People with MCR showed faster rates of decline on figure copy and phonemic fluency. CONCLUSIONS: Gait declines at a faster rate than cognition in aging. People with MCR are susceptible to faster decline in visuospatial, executive, and language functions. This study adds important knowledge of trajectories of gait and cognitive decline in aging, and identifies MCR as a risk factor for accelerated cognitive decline.