Faster Functional Decline Research Articles

STAGING OF PHYSICAL FUNCTIONAL IMPAIRMENT AS A CORRELATE OF GLOBAL COGNITION

Class 2 (n1⁄4211, 17.7%) mildly progressive with intermediate baseline scores on FAQ and ADAS-Cog, worsening on both, but faster functional decline; Class 3 (n1⁄4819, 68.7%) nonprogressive lowest baseline scores on FAQ and ADAS-Cog with minimal change over time. Class 3 participants were less likely to be amyloid positive or carry an APOE 4 allele andmore likely to be an HC or have EMCI at baseline.Conclusions:Cognitive and functional change appears to follow 3 distinct patterns regardless of baseline diagnosis. Amyloid and APOE4 carrier status predict faster decline.

Variants in PPP3R1 and MAPT are associated with more rapid functional decline in Alzheimer's disease: The Cache County Dementia Progression Study

BackgroundSingle-nucleotide polymorphisms (SNPs) located in the gene encoding the regulatory subunit of the protein phosphatase 2B (PPP3R1, rs1868402) and the microtubule-associated protein tau (MAPT, rs3785883) gene were recently associated with higher cerebrospinal fluid (CSF) tau levels in samples from the Knight Alzheimer's Disease Research Center at Washington University (WU) and Alzheimer's Disease Neuroimaging Initiative (ADNI). In these same samples, these SNPs were also associated with faster functional decline, or progression of Alzheimer's disease (AD) as measured by the Clinical Dementia Rating sum of boxes scores (CDR-sb). We attempted to validate the latter association in an independent, population-based sample of incident AD cases from the Cache County Dementia Progression Study (DPS). MethodsAll 92 AD cases from the DPS with a global CDR-sb ≤1 (mild) at initial clinical assessment who were later assessed on CDR-sb data on at least two other time points were genotyped at the two SNPs of interest (rs1868402 and rs3785883). We used linear mixed models to estimate associations between these SNPs and CDR-sb trajectory. All analyses were performed using Proc Mixed in SAS. ResultsAlthough we observed no association between rs3785883 or rs1868402 alone and change in CDR-sb (P > .10), there was a significant association between a combined genotype model and change in CDR-sb: carriers of the high-risk genotypes at both loci progressed >2.9 times faster than noncarriers (P = .015). When data from DPS were combined with previously published data from WU and ADNI, change in CDR-sb was 30% faster for each copy of the high-risk allele at rs3785883 (P = .0082) and carriers of both high-risk genotypes at both loci progressed 6 times faster (P < .0001) than all others combined. ConclusionsWe replicate a previous report by Cruchaga et al that specific variations in rs3785883 and rs1868402 are associated with accelerated progression of AD. Further characterization of this association will provide a better understanding of how genetic factors influence the rate of progression of AD and could provide novel insights into preventative and therapeutic strategies.

Functional Impairment in Peripheral Artery Disease and How to Improve It in 2013

Lower extremity peripheral artery disease (PAD) affects 8 million men and women in the United States and will be increasingly common as the U.S. population lives longer with chronic disease. People with PAD have poorer walking endurance, slower walking velocity, and poorer balance, compared with individuals without PAD. People with PAD may reduce their walking activity to avoid leg symptoms. Thus, clinicians should not equate stabilization or improvement in exertional leg symptoms with stabilization or improvement in walking performance in PAD. In addition, even asymptomatic PAD patients have greater functional impairment and faster functional decline than individuals without PAD. Of the 2 FDA-approved medications for treating claudication symptoms, pentoxifylline may not be more efficacious than placebo, whereas cilostazol confers a modest improvement in treadmill walking performance. Supervised treadmill walking exercise is associated with substantial improvement in walking endurance, but many PAD patients do not have access to supervised exercise programs. Unsupervised walking exercise programs may be beneficial in PAD, but data are mixed.

The Group Oriented Arterial Leg Study (GOALS) to improve walking performance in patients with peripheral arterial disease

People with lower extremity peripheral artery disease (PAD) have greater functional impairment and faster functional decline than those without PAD. We describe methods for the Group Oriented Arterial Leg Study (GOALS), an ongoing randomized controlled clinical trial designed to determine whether a Group-Mediated Cognitive Behavioral (GMCB) intervention improves functional performance in PAD participants, compared to a health education control condition.In GOALS, PAD participants were randomized to either an intervention or a health education control condition in a parallel design. Both conditions consist of weekly group sessions with other PAD participants. In the intervention, cognitive behavioral techniques are used to assist participants in setting and adhering to home-based walking exercise goals. Participants are encouraged to walk for exercise at home at least 5days/week. In the control condition, participants receive lectures on health-related topics. After 6months of on-site weekly sessions, participants are transitioned to telephone follow-up for another 6months. Participants in the intervention are asked to continue home walking exercise. The primary outcome is change in six-minute walk performance between baseline and six-month follow-up. Secondary outcomes include change in six-minute walk performance at 12-month follow-up, and change in treadmill walking performance, the Walking Impairment Questionnaire, quality of life, and physical activity at six and 12-month follow-up. In conclusion, if our group-mediated cognitive behavioral intervention is associated with improved walking performance in individuals with PAD, results will have major public health implications for the large and growing number of people with PAD.

Greater Sedentary Hours and Slower Walking Speed Outside the Home Predict Faster Declines in Functioning and Adverse Calf Muscle Changes in Peripheral Arterial Disease

In participants with peripheral arterial disease (PAD), we determined whether more sedentary behavior and slower outdoor walking speed were associated with faster functional decline and more adverse changes in calf muscle characteristics over time. Modifiable behaviors associated with faster functional decline in lower-extremity PAD are understudied. Participants were 384 men and women with an ankle brachial index <0.90 followed for a median of 47 months. At baseline, participants reported the number of hours they spent sitting per day and their walking speeds outside their homes. Participants underwent baseline and annual measures of objective functional performance. Calf muscle characteristics were measured with computed tomography at baseline and every 2 years subsequently. Analyses were adjusted for age, sex, race, comorbidities, ankle brachial index, and other confounders. Slower walking speed outside the home was associated with faster annual decline in calf muscle density (brisk/striding pace -0.32 g/cm(3), average pace -0.46 g/cm(3), casual strolling -1.03 g/cm(3), no walking at all -1.43 g/cm(3), p trend <0.001). Greater hours sitting per day were associated with faster decline in 6-min walk (<4 h: -35.8 feet/year; 4 to <7 h: -41.1 feet/year; 8 to <11 h: -68.7 feet; ≥12 h: -78.0 feet; p trend = 0.008). Similar associations were observed for greater hours sitting per day and faster declines in fast-paced (p trend = 0.018) and usual-paced (p trend < 0.001) 4-m walking velocity. Greater sedentary hours per day and slower outdoor walking speed are modifiable behaviors that are associated with faster functional decline and greater decline in calf muscle density, respectively, in patients with PAD.

Comorbidity and the rate of cognitive decline in patients with Alzheimer dementia

This study aimed to investigate the impact of comorbidity on cognitive and functional decline in patients with Alzheimer dementia (AD). One hundred and two AD outpatients examined at the Psychiatry Department of the CF2 Polyclinic in Bucharest, Romania and re-evaluated after 2 years. Comorbidity was rated using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Baseline mean age (SD) was 75.4 (8.2) years, median CDR (range) was 2 (1-3), and mean MMSE (SD) 14.2 (4.9). MMSE declined to 11.2 (4.8) during follow-up. Baseline mean total CIRS-G score (SD) was 13.8 (5.4), median number of endorsed categories (range) was 8 (1-14), and mean severity index (SD) 1.9 (0.4). Main comorbidity areas were cardiovascular, ear, nose and throat, genitourinary, musculoskeletal/integument, and neurological. Severity of comorbidity increased with dementia severity (p <0.001). Baseline comorbidity was related to increased rate of cognitive decline; truncated regression coefficients (p-values) were 0.01 (0.02) for CIRS-G total score, and 0.15 (0.006) for severity index (controlled for age, sex, education, and AD treatment). Faster cognitive decline was associated with faster functional decline: OR (95% CI) was 5.2 (1.9-13.6) for increased rate of ADL change and 3.8 (1.0-14.1) for increased rate of IADL change (controlled for age, sex, education, AD medication, and comorbidity). Comorbidity tended to increase functional decline; however, the associations were not statistically significant. In this group of patients with AD, comorbidity increased the rate of cognitive decline. Considering comorbidity instead of focusing on separate conditions may be more helpful in managing AD.

Women With Peripheral Arterial Disease Experience Faster Functional Decline Than Men With Peripheral Arterial Disease

We hypothesized that women with lower extremity peripheral arterial disease (PAD) would have greater mobility loss and faster functional decline than men with PAD. Whether rates of mobility loss or functional decline differ between men and women with PAD is currently unknown. Three hundred eighty men and women with PAD completed the 6-min walk, were assessed for mobility disability, and underwent measures of 4-m walking velocity at baseline and annually for up to 4 years. Computed tomography-assessed calf muscle characteristics were measured biannually. Outcomes included becoming unable to walk for 6 min continuously among participants who walked continuously for 6 min at baseline. Mobility loss was defined as becoming unable to walk for a quarter mile or to walk up and down 1 flight of stairs without assistance among those without baseline mobility disability. Results were adjusted for age, race, body mass index, physical activity, the ankle brachial index, comorbidities, and other confounders. At 4 years of follow-up, women were more likely to become unable to walk for 6 min continuously (hazard ratio: 2.30, 95% confidence interval: 1.30 to 4.06, p = 0.004), more likely to develop mobility disability (hazard ratio: 1.79, 95% confidence interval: 1.30 to 3.03, p = 0.030), and had faster declines in walking velocity (p = 0.022) and the distance achieved in the 6-min walk (p = 0.041) compared with men. Sex differences in functional decline were attenuated after additional adjustment for baseline sex differences in calf muscle area. Women with PAD have faster functional decline and greater mobility loss than men with PAD. These sex differences may be attributable to smaller baseline calf muscle area among women with PAD.

Long-term Outcome and Prediction Models of Activities of Daily Living in Alzheimer Disease With Cholinesterase Inhibitor Treatment

In untreated patients with Alzheimer disease (AD) the functional ability is gradually lost. What happens to the patients after continuous long-term cholinesterase inhibitor (ChEI) treatment is less investigated. The objective of this study was to describe the longitudinal functional outcome and analyze factors affecting the outcome in ChEI-treated patients. In an open, 3-year, nonrandomized, prospective, multicenter study in a routine clinical setting, 790 patients were treated with either donepezil, rivastigmine, or galantamine. At baseline and every 6 months, they were assessed with several rating scales including Instrumental Activities of Daily Living (IADL), Physical Self-Maintenance Scale (PSMS), and Mini-Mental State Examination (MMSE). A faster functional decline was associated with lower cognitive ability at baseline, older age, and the interaction of higher education and longer time in the study. The patients residing with a spouse or relative showed slower deterioration in IADL score. A higher mean dose of ChEI, regardless of drug agent, was also related to slower instrumental ADL decline. Prediction models for longitudinal functional outcome were provided. AD severity at baseline is a key factor in obtaining reliable clinical prognoses of the long-term ADL ability. The dosage of ChEI treatment could possibly lead to a different functional outcome.

Women With Peripheral Arterial Disease Experience Faster Functional Decline Than Men With Peripheral Arterial Disease

Women With Peripheral Arterial Disease Experience Faster Functional Decline Than Men With Peripheral Arterial Disease

Leg Symptom Categories and Rates of Mobility Decline in Peripheral Arterial Disease

To determine whether asymptomatic lower extremity peripheral arterial disease (PAD) and leg symptoms other than intermittent claudication (IC) in PAD are associated with faster functional decline than in people with both PAD and IC. Prospective, observational study. Chicago-area medical center. Four hundred fifteen people with PAD followed annually for up to 7 years. At baseline, patients with PAD were categorized into symptom categories, including IC; leg pain on exertion and rest; participants who could walk through exertional leg pain (pain/carry on); and participants who never experienced exertional leg pain, even during the 6-minute walk (always asymptomatic). Outcomes included mobility loss (becoming unable to walk one-quarter of a mile or walk up and down one flight of stairs without assistance) and becoming unable to complete the 6-minute walk without stopping. Analyses adjusted for age, sex, comorbidities, ankle brachial index, and other confounders. Always-asymptomatic participants (hazard ratio (HR)=2.94, 95% confidence interval (CI)=1.39-6.19, P=.005) and those with leg pain on exertion and rest (HR=2.89, 95% CI=1.47-5.68, P=.002) had greater mobility loss than participants with IC. Participants with PAD with leg pain/carry on were less likely (P=.047) to become unable to walk for 6 minutes continuously without stopping than participants with IC. The ABI identifies patients with asymptomatic PAD and those with atypical leg symptoms who are at risk for greater mobility decline than participants without PAD and participants with PAD with IC.

Baseline Lower Extremity Strength and Subsequent Decline in Functional Performance at 6‐Year Follow‐Up in Persons with Lower Extremity Peripheral Arterial Disease

To evaluate associations between baseline lower extremity strength and decline in functional performance over 6 years of follow-up in men and women with lower extremity peripheral arterial disease (PAD). Prospective observational study. Three Chicago-area hospitals. Three hundred seventy-four men and women with PAD. Baseline isometric hip extension, hip flexion, knee flexion, and knee extension strength were measured using a musculoskeletal fitness evaluation chair. Usual and fastest-paced 4-m walking speed, 6-minute walk, and Short Physical Performance Battery (SPPB) were assessed at baseline and annually thereafter. Analyses were adjusted for age, sex, race, ankle-brachial index (ABI), comorbidities, and other confounders. In women with PAD, weaker baseline hip and knee flexion strength were associated with faster average annual decline in usual-pace 4-m walking speed (P trend <.001 and .02, respectively) and SPPB (P trend=.02 and .01, respectively). In women, weaker hip extension strength was associated with faster decline in usual-pace 4-m walking speed and SPPB (P trend=.01 and <.01, respectively). There were no significant associations between baseline strength and decline in 6-minute walk in women. There were no significant associations between any baseline strength measure and functional decline in men. Weaker baseline leg strength is associated with faster functional decline in nonendurance measures of functional performance in women with PAD but not in men with PAD.

Abstract 5790: High Levels of Homocysteine and D-dimer Are Associated With Faster Functional Decline Among Men and Women With Lower Extremity Peripheral Arterial Disease

BACKGROUND. We assessed associations of baseline biomarker levels with functional decline among participants with lower extremity peripheral arterial disease (PAD). METHODS. Participants were 352 men and women with an ankle brachial index (ABI) &lt; 0.90 who attended a baseline and up to three annual follow-up visits. Baseline levels of homocysteine, C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer were obtained. Participants performed a six-minute walk test and the short physical performance battery (SPPB) at baseline and annually. The SPPB is a composite measure of lower extremity functioning scored on a 0 –12 scale (12= best). Outcomes were average annual decline in six-minute walk distance, average annual decline in the SPPB, and mobility loss. Mobility loss was defined as becoming unable to walk 1/4 mile or walk up and down one flight of stairs without assistance, among those without baseline mobility limitations. Results adjust for age, sex, race, body mass index, ABI, smoking, comorbidities, and other potential confounders. RESULTS . The 352 participants were average age 75±8 and 47% were women. The average ABI was 0.63 ± 0.16 and 33% had diabetes mellitus. Average baseline six-minute walk distance and SPPB scores were 1,101 feet ± 432 and 9 ± 3, respectively. Adjusting for confounders, higher CRP levels were associated with more rapid decline in six-minute walk performance (1 st (lowest) Tertile -50 feet/year; 2 nd Tertile -44 feet/year; 3 rd (highest) Tertile -65 feet/year, p trend value = 0.04). Higher CRP levels were also associated with more rapid decline in the SPPB (1 st (lowest) Tertile 0.3/year; 2 nd Tertile -0.3/year; 3 rd (highest) Tertile -0.5/year, p trend = 0.02). Similarly, higher levels of homocysteine were associated with more rapid decline in the SPPB (1 st Tertile 0.3/year; 2 nd Tertile -0.4/year; 3 rd Tertile -0.5/year, p trend = 0.03). Higher levels of homocysteine were also associated with higher rates of mobility loss, p trend = 0.04). IL-6 and D-dimer were not significantly associated with declining functional performance. CONCLUSIONS . This study demonstrates, for the first time, that higher baseline levels of CRP and homocysteine are associated with faster rates of decline in functional performance among men and women with PAD.

How could the Gompertz–Makeham law evolve

In line with the origin of life from the chemical world, biological mortality kinetics is suggested to originate from chemical decomposition kinetics described by the Arrhenius equation k= A*exp(− E/ RT). Another chemical legacy of living bodies is that, by using the appropriate properties of their constituent molecules, they incorporate all their potencies, including adverse ones. In early evolution, acquiring an ability to use new molecules to increase disintegration barrier E might be associated with new adverse interactions, yielding products that might accumulate in organisms and compromise their viability. Thus, the main variable of the Arrhenius equation changed from T in chemistry to E in biology; mortality turned to rise exponentially as E declined with increasing age; and survivorship patterns turned to feature slow initial and fast late descent making the bulk of each finite cohort to expire within a short final period of its lifespan. Numerical modelling shows that such acquisition of new functions associated with faster functional decline may increase the efficiency of investing resources into progeny, in line with the antagonistic pleiotropy theory of ageing. Any evolved time trajectories of functional changes were translated into changes in mortality through exponent according to the generalised Gompertz–Makeham law μ= C( t)+ Λ*exp[− E( t)], which is reduced to the conventional form when E( t)= E 0 −γt and C is constant. The proposed model explains the origin of the linear mid-age functional decline followed by its deceleration at later ages and the positive correlation between the initial vitality and the rate of ageing.

Disruptive Behavior as a Predictor in Alzheimer Disease

Disruptive behavior is common in Alzheimer disease (AD). There are conflicting reports regarding its ability to predict cognitive decline, functional decline, institutionalization, and mortality. To examine whether the presence of disruptive behavior has predictive value for important outcomes in AD. Using the Columbia University Scale for Psychopathology in Alzheimer Disease (administered every 6 months, for a total of 3438 visit-assessments and an average of 6.9 per patient), the presence of disruptive behavior (wandering, verbal outbursts, physical threats/violence, agitation/restlessness, and sundowning) was extracted and examined as a time-dependent predictor in Cox models. The models controlled for the recruitment cohort, recruitment center, informant status, sex, age, education, a comorbidity index, baseline cognitive and functional performance, and neuroleptic use. Five university-based AD centers in the United States and Europe (Predictors Study). Four hundred ninety-seven patients with early-stage AD (mean Folstein Mini-Mental State Examination score, 20 of 30 at entry) who were recruited and who underwent semiannual follow-up for as long as 14 (mean, 4.4) years. Cognitive (Columbia Mini-Mental State Examination score, < or = 20 of 57 [approximate Folstein Mini-Mental State Examination score, < or = 10 of 30]) and functional (Blessed Dementia Rating Scale score, parts I and II, > or = 10) ratings, institutionalization equivalent index, and death. At least 1 disruptive behavioral symptom was noted in 48% of patients at baseline and in 83% at any evaluation. Their presence was associated with increased risks of cognitive decline (hazard ratio 1.45 [95% confidence interval (CI), 1.03-2.03]), functional decline (1.66 [95% CI, 1.17-2.36]), and institutionalization (1.47 [95% CI, 1.10-1.97]). Sundowning was associated with faster cognitive decline, wandering with faster functional decline and institutionalization, and agitation/restlessness with faster cognitive and functional decline. There was no association between disruptive behavior and mortality (hazard ratio, 0.94 [95% CI, 0.71-1.25]). Disruptive behavior is very common in AD and predicts cognitive decline, functional decline, and institutionalization but not mortality.