A Simplified Proteomics LC-MRM-MS Assay for Determination of apoE Genotypes in Plasma Samples.

Apolipoprotein E (apoE), a polymorphic plasma protein, plays a pivotal role in lipid transportation. The human apoE gene possesses three major alleles (ε2, ε3, and ε4), which differ by single amino acid (cysteine to arginine) substitutions. The ε4 allele represents the primary genetic risk factor for Alzheimer's disease (AD), whereas the ε2 allele protects against the disease. Knowledge of a patient's apoE genotype has high diagnostic value. A recent study has introduced an LC-MRM-MS-based proteomic approach for apoE isoform genotyping using stable isotope-labeled peptide internal standards (SIS). Here, our goal was to develop a simplified LC-MRM-MS assay for identifying apoE genotypes in plasma samples, eliminating the need for the use of SIS peptides. To determine the apoE genotypes, we monitored the chromatographic peak area ratios of isoform-specific peptides relative to a peptide that is common to all apoE isoforms. The assay results correlated well with the standard TaqMan allelic discrimination assay, and we observed a concordance between the two methods for all but three out of 172 samples. DNA sequencing of these three samples has confirmed that the results of the LC-MRM-MS method were correct. Thus, our simplified UPLC-MRM-MS assay is a feasible and reliable method for identifying apoE genotypes without using SIS internal standard peptides. The approach can be seamlessly incorporated into existing quantitative proteomics assays and kits, providing additional valuable apoE genotype information. The principle of using signal ratios of the protein isoform-specific peptides to the peptide common for all of the protein isoforms has the potential to be used for protein isoform determination in general.

Link among apolipoprotein E E4, gait, and cognition in neurodegenerative diseases: ONDRI study.

INTRODUCTION: Apolipoprotein E E4 allele (APOE E4) and slow gait are independently associated with cognitive impairment and dementia. However, it is unknown whether their coexistence is associated with poorer cognitive performance and its underlying mechanism in neurodegenerative diseases. METHODS: Gait speed, APOE E4, cognition, and neuroimaging were assessed in 480 older adults with neurodegeneration. Participants were grouped by APOE E4 presence and slow gait. Mediation analyses were conducted to determine if brain structures could explain the link between these factors and cognitive performance. RESULTS: APOE E4 carriers with slow gait had the lowest global cognitive performance and smaller gray matter volumes compared to non-APOE E4 carriers with normal gait. Coexistence of APOE E4 and slow gait best predicted global and domain-specific poorer cognitive performances, mediated by smaller gray matter volume. DISCUSSION: Gait slowness in APOE E4 carriers with neurodegenerative diseases may indicate extensive gray matter changes associated with poor cognition. HIGHLIGHTS: APOE E4 and slow gait are risk factors for cognitive decline in neurodegenerative diseases. Slow gait and smaller gray matter volumes are associated, independently of APOE E4. Worse cognition in APOE E4 carriers with slow gait is explained by smaller GM volume. Gait slowness in APOE E4 carriers indicates poorer cognition-related brain changes.

White matter hyperintensity burden predicts cognitive but not motor decline in Parkinson's disease: results from the Ontario Neurodegenerative Diseases Research Initiative.

BACKGROUND AND PURPOSE: The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMHs) cognitive and motor impairments seem to be aggravated. However, the role of WMHs in predicting accelerating symptom worsening remains controversial. The objective was to investigate whether location and segmental brain WMH burden at baseline predict cognitive and motor declines in PD after 2 years. METHODS: Ninety-eight older adults followed longitudinally from Ontario Neurodegenerative Diseases Research Initiative with PD of 3-8 years in duration were included. Percentages of WMH volumes at baseline were calculated by location (deep and periventricular) and by brain region (frontal, temporal, parietal, occipital lobes and basal ganglia + thalamus). Cognitive and motor changes were assessed from baseline to 2-year follow-up. Specifically, global cognition, attention, executive function, memory, visuospatial abilities and language were assessed as were motor symptoms evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III, spatial-temporal gait variables, Freezing of Gait Questionnaire and Activities Specific Balance Confidence Scale. RESULTS: Regression analysis adjusted for potential confounders showed that total and periventricular WMHs at baseline predicted decline in global cognition (p < 0.05). Also, total WMH burden predicted the decline of executive function (p < 0.05). Occipital WMH volumes also predicted decline in global cognition, visuomotor attention and visuospatial memory declines (p < 0.05). WMH volumes at baseline did not predict motor decline. CONCLUSION: White matter hyperintensity burden at baseline predicted cognitive but not motor decline in early to mid-stage PD. The motor decline observed after 2 years in these older adults with PD is probably related to the primary neurodegenerative process than comorbid white matter pathology.

Brain Structural Correlates of Obstacle Negotiation in Mild Cognitive Impairment: Results from the Gait and Brain Study.

INTRODUCTION: Mild cognitive impairment (MCI) affects obstacle negotiation capabilities, potentially increasing the risk of falls in older adults. However, it is unclear whether smaller brain volumes typically observed in older individuals with MCI are related to the observed hazardous obstacle negotiation in this population. METHODS: A total of 93 participants (71.9 ± 5.36 years of age; MCI = 53/control = 40) from the Gait and Brain Study were analyzed. Gray matter (GM) volumes from the frontal, temporal, and parietal lobes were entered in the analysis. Gait performance was recorded using a 6-m electronic walkway during two cognitive load conditions while approaching and stepping over an obstacle: (1) single-task and (2) while counting backwards by 1s from 100 (dual-task). Anticipatory adjustments in gait performance to cross an "ad hoc" obstacle were electronically measured during pre-crossing phases: early (3 steps before the late phase) and late (3 steps before obstacle). Association between the percentage of change in average gait speed and step length from early to late (i.e., anticipatory adjustments) and GM volumes was investigated using multivariate models adjusted for potential confounders. RESULTS: Anticipatory adjustments in gait speed (Wilks' lambda: 0.35; Eta2: 0.64; p = 0.01) and step length (Wilks' lambda: 0.33; Eta2: 0.66; p = 0.01) during dual-task conditions were globally associated with GM volumes in MCI. Individuals with MCI with smaller GM volumes in the left inferior frontal gyrus, left hippocampus, right hippocampus, and right entorhinal cortex made significantly fewer anticipatory gait adjustments prior to crossing the obstacle. CONCLUSION: Frontotemporal atrophy may affect obstacle negotiation capabilities potentially increasing the risk of falls in MCI.

Executive dysfunction and effectiveness of physical program in older adults: which association?

BACKGROUND: Little is known about the association between executive function and the magnitude of improvement from personalised exercise interventions on gait performance among older-old adults. AIM: We examined whether the effectiveness of personalised intervention on gait performance is dependent on the patient's baseline dysexecutive syndrome, as assessed by the Frontal Assessment Battery. METHODS: A total of 175 older community-dwellers (83.57 ± 5.2 years; 70.2% female) were recruited from the day centre for after-care and rehabilitation in the Nantes Ambulatory Centre of the Clinical Gerontology (France), and were followed during a pre-post-intervention, single-arm retrospective design. The intervention consisted of an individual personalised rehabilitation program over a period of 7 weeks, with twice-weekly sessions (45 min each). Gait speed in four conditions (preferred, fast, and under two dual-task conditions), Timed Up and Go test, and handgrip strength test were assessed. RESULTS: Using a pre-post analysis of covariance, a significant increase in dual-task gait speed while counting (+ 0.10 m/s; + 15%) and in dual-fluency gait speed (+ 0.06 m/s; + 10%), and in Timed Up and Go performance (- 2.9 s; + 17.8%) was observed after the rehabilitation program, regardless the baseline executive status. DISCUSSION: An individual personalized intervention is effective to improve mobility performance and the dual-task gait speed in older-old adults. The magnitude of those effects is independent of the patient's baseline characteristics including the executive function status. CONCLUSIONS: Even the most deficient baseline characteristics of patients should not be viewed as clinical barrier for implementing a beneficial individual intervention in high-risk older adults.

Dual cognitive and mobility impairments and future dementia - Setting a research agenda.

Dual cognitive and mobility impairments are associated with an increased risk of dementia. Recent studies examining temporal trajectories of mobility and cognitive function in aging found that dual decline is associated with higher dementia risk than memory decline or gait decline only. Although initial data show that individuals with dual decline or impairment have excessive cardiovascular and metabolic risk factors, the causes of dual decline or what underlies dual decline with a high risk of dementia remain largely unknown. In December 2021, the National Institute on Aging Intramural and Extramural Programs jointly organized a workshop on Biology Underlying Moving and Thinking to explore the hypothesis that older persons with dual decline may develop dementia through a specific pathophysiological pathway. The working group discussed assessment methods for dual decline and possible mechanisms connecting dual decline with dementia risk and pinpointed the most critical questions to be addressed from a translational perspective.

Characteristics of the Ontario Neurodegenerative Disease Research Initiative cohort.

INTRODUCTION: Understanding synergies between neurodegenerative and cerebrovascular pathologies that modify dementia presentation represents an important knowledge gap. METHODS: This multi-site, longitudinal, observational cohort study recruited participants across prevalent neurodegenerative diseases and cerebrovascular disease and assessed participants comprehensively across modalities. We describe univariate and multivariate baseline features of the cohort and summarize recruitment, data collection, and curation processes. RESULTS: We enrolled 520 participants across five neurodegenerative and cerebrovascular diseases. Median age was 69 years, median Montreal Cognitive Assessment score was 25, median independence in activities of daily living was 100% for basic and 93% for instrumental activities. Spousal study partners predominated; participants were often male, White, and more educated. Milder disease stages predominated, yet cohorts reflect clinical presentation. DISCUSSION: Data will be shared with the global scientific community. Within-disease and disease-agnostic approaches are expected to identify markers of severity, progression, and therapy targets. Sampling characteristics also provide guidance for future study design.

Medication reviews and deprescribing as a single intervention in falls prevention: a systematic review and meta-analysis.

BACKGROUND: our aim was to assess the effectiveness of medication review and deprescribing interventions as a single intervention in falls prevention. DESIGN: systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane CENTRAL, PsycINFO until 28 March 2022. ELIGIBILITY CRITERIA: randomised controlled trials of older participants comparing any medication review or deprescribing intervention with usual care and reporting falls as an outcome. STUDY RECORDS: title/abstract and full-text screening by two reviewers. RISK OF BIAS: Cochrane Collaboration revised tool. DATA SYNTHESIS: results reported separately for different settings and sufficiently comparable studies meta-analysed. RESULTS: forty-nine heterogeneous studies were included. COMMUNITY: meta-analyses of medication reviews resulted in a risk ratio (RR) of 1.05 (95% confidence interval, 0.85-1.29, I2 = 0%, 3 studies(s)) for number of fallers, in an RR = 0.95 (0.70-1.27, I2 = 37%, 3 s) for number of injurious fallers and in a rate ratio (RaR) of 0.89 (0.69-1.14, I2 = 0%, 2 s) for injurious falls. HOSPITAL: meta-analyses assessing medication reviews resulted in an RR = 0.97 (0.74-1.28, I2 = 15%, 2 s) and in an RR = 0.50 (0.07-3.50, I2 = 72% %, 2 s) for number of fallers after and during admission, respectively. LONG-TERM CARE: meta-analyses investigating medication reviews or deprescribing plans resulted in an RR = 0.86 (0.72-1.02, I2 = 0%, 5 s) for number of fallers and in an RaR = 0.93 (0.64-1.35, I2 = 92%, 7 s) for number of falls. CONCLUSIONS: the heterogeneity of the interventions precluded us to estimate the exact effect of medication review and deprescribing as a single intervention. For future studies, more comparability is warranted. These interventions should not be implemented as a stand-alone strategy in falls prevention but included in multimodal strategies due to the multifactorial nature of falls.PROSPERO registration number: CRD42020218231.

World guidelines for falls prevention and management for older adults: a global initiative.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. OBJECTIVES: to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders; (ii) gaps in previous guidelines; (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries. METHODS: a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting. RECOMMENDATIONS: all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. CONCLUSIONS: the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources.

Geriatric co-management and interdisciplinary transitional care reduced hospital readmissions in frail older patients in Argentina: results from a randomized controlled trial.

BACKGROUND: Hospitalization is a moment of extreme vulnerability for frail older adults. There is scarce evidence on the effectiveness of geriatric co-management or transitional care interventions in Latin America. AIMS: To assess whether geriatric co-management combined with an interdisciplinary transitional care intervention could reduce 30-day hospital readmission rate compared to usual care in hospitalized frail older patients in a tertiary hospital in Argentina. METHODS: Single-blinded randomized controlled trial. Usual care treatment arm: all procedures performed during hospitalization were overseen by a senior internal medicine specialist and complied with pre-defined protocols. Patients had access to specialist care if needed, as well as hospital-at-home or home-based primary care services after discharge. Intervention treatment arm: in addition to usual care, a geriatric co-management team performed a comprehensive geriatric assessment during hospitalization, provided tailored recommendations to minimize geriatric syndromes and planned transition of care. A health and social care counselor oversaw continuity of care in patients' homes after discharge. RESULTS: We included 120 participants in each of the intervention and usual care (control) arms. Thirty-day hospital readmissions were 47.7% lower in the intervention arm (18.3% vs 35.0%; P = 0.040); and emergency room visits within the first 6 months after discharge were 27.8% lower (43.3% vs 60.0%; P = 0.010). There was a non-statistically significant decrease in 6-month mortality in the intervention arm (25.0% vs 35.0%; P = 0.124). CONCLUSION: Geriatric co-management of frail older patients during hospitalization combined with an interdisciplinary transitional care intervention reduced 30-day hospital readmissions and emergency visits 6 months after discharge. TRIAL REGISTRATION NUMBER: Trial registration number: RENIS IS003081.

How Long Should GPS Recording Lengths Be to Capture the Community Mobility of An Older Clinical Population? A Parkinson's Example.

Wearable global position system (GPS) technology can help those working with older populations and people living with movement disorders monitor and maintain their mobility level. Health research using GPS often employs inconsistent recording lengths due to the lack of a standard minimum GPS recording length for a clinical context. Our work aimed to recommend a GPS recording length for an older clinical population. Over 14 days, 70 older adults with Parkinson's disease wore the wireless inertial motion unit with GPS (WIMU-GPS) during waking hours to capture daily "time outside", "trip count", "hotspots count" and "area size travelled". The longest recording length accounting for weekend and weekdays was ≥7 days of ≥800 daily minutes of data (14 participants with 156, 483.9 min recorded). We compared the error rate generated when using data based on recording lengths shorter than this sample. The smallest percentage errors were observed across all outcomes, except "hotspots count", with daily recordings ≥500 min (8.3 h). Eight recording days will capture mobility variability throughout days of the week. This study adds empirical evidence to the sensor literature on the required minimum duration of GPS recording.

The apathy, gait impairment, and executive dysfunction (AGED) triad vascular variant.

Apathy, gait disturbances, and executive dysfunction (AGED) often occur together. Although they can arise independently, the presence of one might portend another. This recognition suggests the possible etiology. We focus on the most common, the vascular. We explain the AGED vascular mechanism through the ambibaric brain concept. The brain contains two complementary blood pressure systems: One high in the primitive brain (brainstem, basal ganglia, and thalamus) and a low-pressure system in the Homo sapiens brain (cerebral hemispheres). Hypertension inflicts the most damage on the primitive brain. The frontal systems connect to the basal ganglia, then the thalamus and back to the cortex. Many connections converge on the primitive brain where they are damaged by vascular disease. We need methods of determining optimal, individual blood pressures. Although the AGED triad can result from other causes, it should first signal a vascular etiology, the most prevalent, treatable, and preventable one.

New horizons in falls prevention and management for older adults: a global initiative.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects both on quality of life and functional independence and are associated with increased morbidity, mortality and health care costs. Current clinical approaches and advice from falls guidelines vary substantially between countries and settings, warranting a standardised approach. At the first World Congress on Falls and Postural Instability in Kuala Lumpur, Malaysia, in December 2019, a worldwide task force of experts in falls in older adults, committed to achieving a global consensus on updating clinical practice guidelines for falls prevention and management by incorporating current and emerging evidence in falls research. Moreover, the importance of taking a person-centred approach and including perspectives from patients, caregivers and other stakeholders was recognised as important components of this endeavour. Finally, the need to specifically include recent developments in e-health was acknowledged, as well as the importance of addressing differences between settings and including developing countries. METHODS: a steering committee was assembled and 10 working Groups were created to provide preliminary evidence-based recommendations. A cross-cutting theme on patient's perspective was also created. In addition, a worldwide multidisciplinary group of experts and stakeholders, to review the proposed recommendations and to participate in a Delphi process to achieve consensus for the final recommendations, was brought together. CONCLUSION: in this New Horizons article, the global challenges in falls prevention are depicted, the goals of the worldwide task force are summarised and the conceptual framework for development of a global falls prevention and management guideline is presented.

Impact of an individual personalised rehabilitation program on mobility performance in older-old people.

BACKGROUND: Studies have shown benefits of exercise interventions on preferred and fast gait speed in healthy older adults, but the impact of a personalised rehabilitation program targeting a large cohort of non-disabled older-old adults has rarely been examined. AIMS: The purpose was to determine whether personalised intervention-related improvements in gait and mobility performance in older-old adults were dependent on cognitive status and/or history of falls. METHODS: Based on a pre-post design, 483 older-old persons (mean age: 83.3 ± 5.1 years) were followed during a personalised rehabilitation program over a period of 7 weeks, with twice-weekly sessions (45 min each). Gait speed in four conditions (preferred, fast, and under two dual-task conditions), static postural sway, Timed Up and Go test, Five Times Sit to Stand test, the ability to rise from the floor, and handgrip strength test were assessed. RESULTS: Using a pre-post analysis of covariance, a significant increase in preferred gait speed (+ 20.1%), fast gait speed (+ 15.8%), and dual-task speed while counting (+ 13.4%) was observed after the rehabilitation, regardless of the baseline cognitive status and fall history. Similar improvements in TUG and maximal handgrip force were observed, with a significant reduction of performance time (-19.5%) or an increase of handgrip strength (+ 6.2%). DISCUSSION: Results suggest the effectiveness of personalised intervention to improve a battery of physical performance measures in older-old adults, even for the frailest participants. CONCLUSION: Implementing a personalised intervention for targeting the high-risk older-old adults in priority is critical regarding the clinically meaningful change in gait speed.

A multifactorial intervention to lower potentially inappropriate medication use in older adults in Argentina.

BACKGROUND: Adverse drug reactions are a common cause of potentially avoidable harm, particularly in older adults. AIMS: To evaluate the feasibility and efficacy of a pilot multifactorial intervention to reduce potentially inappropriate medication (PIM) use in older adults. METHODS: We conducted a phase 2, feasibility, open-label study in the ambulatory setting of an integrated healthcare network in Buenos Aires, Argentina. We recruited primary care physicians (PCPs) and measured PIM use in a sample of their patients (65 years or older). Educational workshops for PCPs were organized with the involvement of clinician champions. Practical deprescribing algorithms were designed based on Beers criteria. Automatic email alerts based on specific PIMs recorded in each patient's electronic health record were used as a reminder tool. PCPs were responsible for deprescribing decisions. We randomly sampled 879 patients taking PIMs from eight of the most commonly used drug classes at our institution and compared basal (6 months prior to the intervention) and final (12 months after) prevalence of PIM use using a test of proportions. RESULTS: There was a significant reduction (p < 0.05) in all drug classes evaluated. Non-Steroidal Anti-Inflammatory Drugs (basal prevalence 5.92%; final 1.59%); benzodiazepines (10.13%; 6.94%); histamine antagonists (7.74%; 3.07%); opioids (2.16%; 1.25%); tricyclic antidepressants (8.08%; 4.10%); muscle relaxants (7.74%; 3.41%), anti-hypertensives (3.53%; 1.82%) and oxybutynin (2.96%; 1.82%). The absolute reduction in the overall prevalence was 8.5 percentage points (relative reduction of 51.4%). CONCLUSION: This multifactorial intervention is feasible and effective in reducing the use of potentially inappropriate medication in all drug classes evaluated.

Gait variability across neurodegenerative and cognitive disorders: Results from the Canadian Consortium of Neurodegeneration in Aging (CCNA) and the Gait and Brain Study.

INTRODUCTION: Gait impairment is common in neurodegenerative disorders. Specifically, gait variability-the stride-to-stride fluctuations in distance and time-has been associated with neurodegeneration and cognitive impairment. However, quantitative comparisons of gait impairments across the cognitive spectrum of dementias have not been systematically investigated. METHODS: Older adults (N = 500) with subjective cognitive impairment, Parkinson disease (PD), mild cognitive impairment (MCI), PD-MCI, Alzheimer's disease (AD), PD-dementia, Lewy body dementia, and frontotemporal dementia, as well cognitive normal controls, who were assessed for their gait and cognitive performance. RESULTS: Factor analyses grouped 11 quantitative gait parameters and identified four independent gait domains: rhythm, pace, variability, and postural control, for group comparisons and classification analysis. Among these domains, only high gait variability was associated with lower cognitive performance and accurately discriminated AD from other neurodegenerative and cognitive conditions. DISCUSSION: Our findings indicate that high gait variability is a marker of cognitive-cortical dysfunction, which can help to identify Alzheimer's disease dementia.

Dual decline in gait speed and cognition is associated with future dementia: evidence for a phenotype.

BACKGROUND: concurrent declines in gait speed and cognition have been associated with future dementia. However, the clinical profile of 'dual decliners', those with concomitant decline in both gait speed and cognition, has not been yet described. We aimed to describe the phenotype and the risk for incident dementia of those who present with dual decline in comparison with non-dual decliners. METHODS: prospective cohort of community-dwelling older adults free of dementia at baseline. We evaluated participants' gait speed, cognition, medical status, functionality, incidence of adverse events and dementia, biannually over 7 years. Gait speed was assessed with a 6-m electronic walkway and global cognition using the MoCA test. We compared characteristics between dual decliners and non-dual decliners using t-test, chi-square and hierarchical regression models. We estimated incident dementia using Cox models. RESULTS: among 144 participants (mean age 74.23 ± 6.72 years, 54% women), 17% progressed to dementia. Dual decliners had a 3-fold risk (HR: 3.12, 95%CI: 1.23-7.93, P = 0.017) of progression to dementia compared with non-dual decliners. Dual decliners were significantly older with a higher prevalence of hypertension and dyslipidemia (P = 0.002). Hierarchical regression models show that age and sex alone explained 3% of the variation in the dual decliners group. Adding hypertension and dyslipidemia increased the explained variation by 8 and 10%, respectively. The risk of becoming a dual decliner was 4-fold higher if hypertension was present. CONCLUSION: older adults with a concurrent decline in gait speed and cognition represent a group at the highest risk of progression to dementia. Older adults with dual decline have a distinct phenotype with a higher prevalence of hypertension, a treatable condition.

Recommendations of the 5th Canadian Consensus Conference on the diagnosis and treatment of dementia.

Since 1989, four Canadian Consensus Conferences on the Diagnosis and Treatment of Dementia (CCCDTD) have provided evidence-based dementia guidelines for Canadian clinicians and researchers. We present the results of the 5th CCCDTD, which convened in October 2019, to address topics chosen by the steering committee to reflect advances in the field, and build on previous guidelines. Topics included: (1) utility of the National Institute on Aging research framework for clinical Alzheimer's disease (AD) diagnosis; (2) updating diagnostic criteria for vascular cognitive impairment, and its management; (3) dementia case finding and detection; (4) neuroimaging and fluid biomarkers in diagnosis; (5) use of non-cognitive markers of dementia for better dementia detection; (6) risk reduction/prevention; (7) psychosocial and non-pharmacological interventions; and (8) deprescription of medications used to treat dementia. We hope the guidelines are useful for clinicians, researchers, policy makers, and the lay public, to inform a current and evidence-based approach to dementia.

World-Wide FINGERS Network: A global approach to risk reduction and prevention of dementia.

Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.

Does Dual-Task Gait Differ in those with Late-Life Depression versus Mild Cognitive Impairment?

OBJECTIVES: To compare the dual-task gait performance of older adults with Late-Life Depression (LLD) versus Mild Cognitive Impairment (MCI). DESIGN: Cross-sectional study with three matched groups: LLD, MCI and non-depressed and cognitively intact (NDCI). SETTING: LLD group participants were recruited from geriatric psychiatry clinics in London, Ontario. Matched participants meeting criteria for the MCI or NDCI groups were previously recruited for other research studies from geriatric clinics and the community. PARTICIPANTS: Individuals aged 60-85 who met criteria for mild-moderate LLD (N=23) without a diagnosis of a neurocognitive disorder. MEASUREMENTS: Participants completed questionnaires regarding mood, cognition and physical activity. Gait speed was recorded using an electronic walkway during simple and dual-task gait (walking while naming animals aloud). Dual-task cost (DTC) is the percentage change in gait speed between simple and dual-task gait. It is a clinically relevant indicator of fall risk and is strongly associated with cognitive decline. For comparison, 23 MCI and 23 NDCI participants, matched with respect to age, sex and comorbidities, were randomly selected from existing research databases. RESULTS: Each group had 8 males and 15 females, with mean age of 69.0-69.6 years. The mean (±SD) DTC of the NDCI, LLD and MCI groups were statistically different at 2.4±11.4%, 11.8±9.9% and 22.2±16.7%, respectively. CONCLUSION: Older adults with LLD perform worse on dual-task gait than NDCI; however, they are less impaired than those with MCI. The elevated DTC seen in LLD is likely because of underlying executive dysfunction that is less significant than in those with MCI.