A genome‐wide association meta‐analysis of all‐cause and vascular dementia

Introduction: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD. Methods: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors. Results: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability (ANO3), amyloid deposition in the brain (RBFOX1), and magnetic resonance imaging markers of small vessel disease (SVD; HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, and PSMA3). Discussion: Our study identified genetic risks underlying ACD, demonstrating overlap with neurodegenerative processes, vascular risk factors, and cerebral SVD. Highlights: We conducted the largest genome-wide association study of all-cause dementia (ACD) and vascular dementia (VaD). Known genetic variants associated with AD were replicated for ACD and VaD. Functional analyses identified novel loci for ACD and VaD. Genetic risks of ACD overlapped with neurodegeneration, vascular risk factors, and cerebral small vessel disease

Association between cognitive impairment and criteria for frailty syndrome among older adults

OBJECTIVE: The association between cognitive impairment and physical frailty has been studied in older adults. The criteria degree of frailty may be keys to associated cognitive impairment. To analyze the association between cognitive impairment and the criteria for frailty. METHODS: We cross-sectionally examined data from 667 older adults (≥60 years of age) from a study entitled 'Variables associated to cognition in elderly caregivers' involving patients in an urban and rural primary healthcare center. We defined cognitive impairment based on different groups of scores on the Mini Mental State Examination, and defined frailty and prefrailty using the criteria by the Cardiovascular Health Study. We performed multinomial regression models to analyze the association between levels of frailty and cognitive impairment. RESULTS: Similar proportions of women (54.8%) and men (45.2%) participated in the study (mean age: 71 years old). We found cognitive impairment, prefrailty and frailty in 34, 54, and 24% of the participants, respectively. Concomitant cognitive impairment and frailty was found in 13% of them. The chances of cognitive impairment increased up to 330% (Odds Ratio [OR]: 4.3; 95% confidence interval [95%CI] 2.4‒7.7; p<0.001) among frail individuals, and 70% (OR: 1.7; 95%CI 1.0‒2.8; p=0.033) among prefrail individuals compared to robust/non-frail individuals. After controlling for age, education, place of residence and functional dependence, slowness and fatigue criteria were significantly associated with cognitive impairment. CONCLUSION: Older adults with frailty have a greater likelihood of concomitant cognitive impairment than prefrail and robust older adults. The prevalence of cognitive impairment and frailty is consistent with data reported in literature. The present findings contribute to the investigation of cognitive frailty

Dissociation of Alzheimer&#x27;s morphological pathology from cognitive impairment

We observed the Alzheimer&#x27;s morphological pathology, amyloid production induces Alzheimer&#x27;s cognitive impairment, was dissociated from the cognitive impairment. The earlier Alzheimer&#x27;s pathological changes can be induced in normal C57BL mice, by B6 deficient feeding 4 months with no amyloid, and this cognitive and memory impairments were completely inhibited by anti-homocysteic acid antibody. According to Koch&#x27;s postulate, if a pathogen of Alzheimer&#x27;s disease is administrated to the normal animal, we would observe the Alzheimer&#x27;s cognitive impairment in the normal animal. We actually have observed this cognitive impairment in normal C57BL male mice with no amyloid. From our observations, it is suggested the dissociation of Alzheimer&#x27;s morphological pathology may be possible from the cognitive impairment

Hemostasis biomarkers and incident cognitive impairment: the REGARDS study

Essentials Cognitive disorders are increasing and vascular risk factors play a role in this. We performed a nested case control study of hemostasis biomarkers and cognitive impairment (CI). Higher baseline fibrinogen, factor VIII and D-dimer were related to incident CI over 3.5 years. Adjusted for other risk factors, 2+ abnormal markers (but not single ones) led to higher risk. SUMMARY: Background Vascular risk factors are associated with cognitive impairment, a condition that imposes a substantial public health burden. We hypothesized that hemostasis biomarkers related to vascular disease would be associated with the risk of incident cognitive impairment. Methods We performed a nested case-control study including 1082 participants with 3.5 years of follow-up in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a longitudinal cohort study of 30 239 black and white Americans aged ≥ 45 years. Participants were free of stroke or cognitive impairment at baseline. Baseline D-dimer, fibrinogen, factor VIII and protein C levels were measured in 495 cases who developed cognitive impairment during follow-up (based on abnormal scores on two or more of three cognitive tests) and 587 controls. Results Unadjusted odds ratios (ORs) for incident cognitive impairment were 1.32 (95% confidence interval [CI] 1.02-1.70) for D-dimer > 0.50 μg mL-1 , 1.83 (95% CI 1.24-2.71) for fibrinogen > 90th percentile, 1.63 (95% CI 1.11-2.38) for FVIII > 90th percentile, and 1.10 (95% CI 0.73-1.65) for protein C < 10th percentile. There were no differences in associations by race or region. Adjustment for demographic, vascular and health behavior risk factors attenuated these associations. However, having at least two elevated biomarkers was associated with incident cognitive impairment, with an adjusted OR of 1.73 (95% CI 1.10-2.69). Conclusion Elevated D-dimer, fibrinogen and FVIII levels were not associated with the occurrence of cognitive impairment after multivariable adjustment; however, having at least two abnormal biomarkers was associated with the occurrence of cognitive impairment, suggesting that the burden of these biomarkers is relevant

Gait and Balance in Alzheimer\u27s Disease: A Retrospective Analysis Across Varying Levels of Cognitive Impairment

Background: It was once thought that Alzheimer’s disease (AD) affected mostly cognition with minor motor impairment; however, it is becoming apparent that motor impairment may also be a prominent feature. Determining the extent of motor impairments throughout the continuum of cognitive impairment is critical in developing timely interventions for this population. Purpose/Hypothesis: The aim of this study was to gain a greater understanding of motor impairment in AD by exploring the relationships among gait, balance, and falls. Specifically, we explored the association of fall history to measures of cognition and performance-based balance measures in individuals with AD. We hypothesized that falls would increase as balance impairments became more severe. Additionally, we mapped the trajectory of gait and balance function along the continuum of cognitive impairment in individuals with AD. We hypothesized that balance and gait would be worse for those in the lower quartiles of cognitive function compared to those in the upper quartiles. Lastly, we sought to determine if fall history worsened as cognition declined. We hypothesized that falls history would be worse in lower quartiles of cognitive impairment compared to upper quartiles of cognitive impairment. Subjects: Retrospective data of 419 patients with brain health conditions and an initial evaluation for physical therapy at the Cleveland Clinic Lou Ruvo Center for Brain Health were extracted from electronic records. Of those 419, 155 were diagnosed by a neurologist with AD (age=77.4 ± 9.5; 69 males, 86 females) and were subsequently analyzed for this study. Materials/Methods: Patients were stratified into cognitive quartiles using scores from the Montreal Cognitive Assessment (MoCA): 0-9 (very severe cognitive impairment), 10-14 (severe cognitive impairment), 15-20 (Moderate to severe impairment), 21-30 (mild to moderate impairment). These cognitive function quartiles were then compared across the following measures: fall history (falls in last year, falls in the last 30 days, and fall injuries in the last year), 5 times Sit To Stand (5STS), Timed Up and Go (TUG), TUG cognitive (TUGcog), Preferred Gait Speed (PGS), Fast Gait Speed (FGS), 6 Minute Walk Test (6MWT), and Mini Balance Evaluation Systems Test (MBT). Results: For our first aim, there were no statistically significant differences between fallers and non-fallers for cognition, age, and measures of gait and balance (ps≥.068), except non-fallers walked farther on the 6MWT (p=.030). There were no statistically significant differences for recent (last 30 days) fallers and non-fallers across the same measures (ps≥.082). Fallers who had experienced an injury as a result of a fall in the last year performed more poorly on the 6MWT (p=.034) and MBT SOT (p=.008); all other comparisons were not statistically significant (ps≥.085). For our second aim, there were no statistically significant differences among the four cognitive quartiles for 5STS (p=.456), TUG (p=.060), FGS (p=.181), 6MWT (p=.468), MBT (p=.321); however, there were for TUGcog (p=.046) and PGS (p=.033). The mild to moderate impairment quartile was significantly faster than the severe quartile (p=.006) for the TUGcog. For PGS, the mild to moderate was significantly faster than the very severe quartile (p=.039) and the moderate to severe was significantly faster than the severe and the very severe quartiles (severe, p=.036; and, very severe, p=.016). For our third aim, there were no statistically significant differences in the proportions of fallers (p=.636), recent fallers (p=.868), and injured fallers (p=.565) across the four cognitive quartiles. Discussion: Despite impairments recognized in our study compared to normative data, patients in the study with a fall history were not significantly worse across most measures of gait and balance, except fallers had poorer walking endurance as measured in the 6MWT. Additionally, the proportion of fallers did not increase as severity of cognitive impairment increased, although walking impairment as measured with PGS and TUGcog, especially with cognitive demand, is more prominent in those with more severe cognitive impairment. Conclusions: Balance and gait dysfunction were prominent at all levels of cognitive impairment in our study of patients with AD and appears to become more prominent at the most severe cognitive impairment levels. These progressive deficits represent potentially mitigable motor impairment features of AD that warrant physical therapy

User-driven design of robot costume for child-robot interactions among children with cognitive impairment

The involvement of arts and psychology elements in robotics research for children with cognitive impairment is still limited. However, the combination of robots, arts, psychology and education in the development of robots could significantly contribute to the improvement of social interaction skills among children with cognitive impairment. In this article, we would like to share our work on building and innovating the costume of LUCA's robot, which incorporating the positive psychological perspectives and arts values for children with cognitive impairment. Our goals are (1) to educate arts students in secondary arts school on the importance of social robot appearance for children with cognitive impairment, and (2) to select the best costume for future child-robot interaction study with children with cognitive impairments

Implementation of the Vermont Mini-Cog

Cognitive impairment screening is important for early detection, diagnosis, and treatment of cognitive impairment and dementia. Additionally, screening is mandated as part of the Medicare Annual Wellness Visit. Colchester Family Medicine providers were surveyed about their current screening behaviors and then provided a training session on cognitive impairment screening and the Vermont Mini-Cog screening tool. Post-training, providers were surveyed about their likely future screening practices.https://scholarworks.uvm.edu/fmclerk/1540/thumbnail.jp

Caring for the older person with cognitive impairment in hospital: Qualitative analysis of nursing personnel reflections on fall events

Aims and objectives To explore nurse and nursing assistant reflections on the care of older patients with cognitive impairment who have experienced a fall. Background While there are evidence‐based clinical guidelines for the prevention and management of falls and for the care of older people with cognitive impairment, the falls rates for older people with cognitive impairment are three times as high as those without. Design Critical incident technique. Methods Eleven registered and two enrolled nurses and four assistants in nursing working in one subacute and two acute wards within two hospitals of a tertiary level health service in south‐east Queensland. Individual semistructured interviews focused on two past events when a patient with cognitive impairment had fallen in hospital: one when there was minimal harm and the second when there was significant harm. Thematic analysis was undertaken. The COREQ checklist was followed. Results Three themes emerged from 23 reflective accounts of fall events: “direct observation is confounded by multiple observers” and “knowing the person has cognitive impairment is not enough,” and “want to rely on the guideline but unsure how to enact it.” While participants were aware of the falls prevention policy and techniques available to prevent falls, the implementation of these was challenging due to the complexity of care required by the older person with cognitive impairment. Conclusions Falls prevention for older people with cognitive impairment is complex and belies the simple application of policy. Relevance to clinical practice To reduce falls, nurses can involve the family to support “knowing the patient” to enable prediction of impulsive actions; shift the focus of in‐service from lectures to specific case presentations, with collaborative analysis on person‐focused strategies to prevent falls in older people with cognitive impairment; and reconsider the sitter role from simple observer to assistant, focused on ambulation and supporting independence in activities of daily living.Full Tex

Sickle cell trait and risk of cognitive impairment in African-Americans: The REGARDS cohort

Background: Sickle cell anemia may be associated with cognitive dysfunction, and some complications of sickle cell anemia might affect those with sickle cell trait (SCT), so we hypothesized that SCT is a risk factor for cognitive impairment. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled a national cohort of 30,239 white and black Americans from 2003 to 7, who are followed every 6 months. Baseline and annual global cognitive function testing used the Six-Item Screener (SIS), a validated instrument (scores range 0-6; ≤ 4 indicates cognitive impairment). Participants with baseline cognitive impairment and whites were excluded. Logistic regression was used to calculate the association of SCT with incident cognitive impairment, adjusted for risk factors. Linear mixed models assessed multivariable-adjusted change in test scores on a biennially administered 3-test battery measuring learning, memory, and semantic and phonemic fluency. Findings: Among 7743 participants followed for a median of 7·1 years, 85 of 583 participants with SCT (14·6%) developed incident cognitive impairment compared to 902 of 7160 (12·6%) without SCT. In univariate analysis, the odds ratio (OR) of incident cognitive impairment was 1·18 (95% CI: 0·93, 1·51) for those with SCT vs. those without. Adjustment did not impact the OR. There was no difference in change on 3-test battery scores by SCT status (all p > 0·11). Interpretation: In this prospective cohort study of black Americans, SCT was not associated with incident cognitive impairment or decline in test scores of learning, memory and executive function. Funding: National Institutes of Health, American Society of Hematology

Cognitive impairment in older people: its implications for future demand for services and costs

This study aimed to make projections, for the next 30 years, of future numbers of older people with cognitive impairment, their demand for long-term care services and the future costs of their care under a range of specified assumptions. Cognitive impairment is one of the manifestations of dementia. The most common dementia syndrome is Alzheimer’s Disease (AD), followed by vascular dementia (Henderson and Jorm, 2000). It also set out to explore the factors that are likely to affect future long-term care expenditure associated with cognitive impairment. These factors include, not only future numbers of older people and future prevalence rates of cognitive impairment, but also trends in household composition, provision of informal care, patterns of care services and the unit costs of care