Dual-tasks and walking fast: relationship to extra-pyramidal signs in advanced Alzheimer disease

Extra-pyramidal signs (EPS) and cadence predicted falls risk in patients with advanced Alzheimer disease (AD). Dual task performance predicts falls with variable success. Dual-task performance and walking fast were examined in advanced AD patients with EPS (EPS+, >3 modified Unified Parkinson's Disease Rating Scale [UPDRS] signs) or without EPS (EPS-, three or less UPDRS signs). Demographics, mental and functional status, behavioral impairment, EPS, and quantitative gait measures (GaitRite) were determined. The effects of an automatic dual-task (simple counting) and of walking fast on spatial and temporal gait characteristics were compared between EPS+ and EPS- subjects using a repeated measures design. Cadence decreased, while stride time, swing time and variability in swing time increased with the dual task. Results were insignificant after adjusting for secondary task performance. With walking fast, speed, cadence and stride length increased while stride time, swing time and double support time decreased. Although EPS+ subjects were slower and had decreased stride length, dual task and walking fast effects did not differ from EPS- subjects. Patient characteristics, the type of secondary task and the specific gait measures examined vary in the literature. In this moderately to severely demented population, EPS did not affect "unconscious" (dual task) or "conscious" (walking fast) gait modulation. Given their high falls risk, and retained ability to modulate walking, EPS+ AD patients may be ideal candidates for interventions aimed at preventing falls.     

C‐reactive protein levels and common polymorphisms of the interleukin‐1 gene cluster and interleukin‐6 gene in patients with coronary heart disease

C‐reactive protein (CRP) is an inflammatory marker associated with increased cardiovascular risk. Production of CRP is regulated by interleukin (IL)‐1β, IL‐1 receptor antagonist and IL‐6. In 160 patients with coronary heart disease (CHD) confirmed by angiography, we examined the relationship between CRP level and five polymorphisms in genes coding for these cytokines: IL‐1B(?511), IL‐1B(+3954), a variable number tandem repeat (VNTR) polymorphism in intron 2 of IL‐1RN [IL‐1RN(VNTR)], IL‐6(?174) and IL‐6(?572). CRP values were logarithmically normalized (log‐CRP) for statistical calculations. In univariate analysis, carrier status for the IL‐1B(+3954)T allele and IL‐1RN(VNTR) allele 2 [IL‐1RN(VNTR)*2] correlated with higher (P < 0.01) and lower (P < 0.05) log‐CRP values, respectively. Among the potential confounding factors analysed, smoking, body mass index, total cholesterol (P < 0.05 for all) and diabetes (P = 0.056) were positively correlated with CRP level. After adjustment for non‐genetic covariates, CRP levels remained significantly (P < 0.01) higher in carriers of IL‐1B(+3954)T than in non‐carriers: mean log‐CRP (with 95% confidence interval) was 0.443 (0.311–0.574) for CT or TT genotypes compared with 0.240 (0.107–0.373) for the CC genotype, which corresponded to back‐transformed CRP levels of 2.77 and 1.74 mg l^?1, respectively. Adjusted association was also significant for IL‐1RN(VNTR)*2 (P < 0.01), with lower CRP levels in the presence of allele 2: the mean log‐CRP value was 0.252 (0.115–0.388) for carriers and 0.421 (0.290–0.552) for non‐carriers (CRP 1.79 and 2.64 mg l^?1, respectively). When alleles of both polymorphisms were entered into the model simultaneously, the association remained significant for IL‐1B(+3954)T (P < 0.05), but not for IL‐1RN(VNTR)*2. We conclude that IL‐1B(+3954)T is associated with higher CRP levels in patients with CHD, and we found that this association was significant after adjustment for major risk factors. Our data also suggest a possible relationship of IL‐1RN(VNTR)*2 with lower CRP levels in the same patients.     

Forced retroevolution of an RNA bacteriophage

The operator hairpin ahead of the replicase gene in RNA bacteriophage MS2 contains overlapping signals for binding the coat protein and ribosomes. Coat protein binding inhibits further translation of the gene and forms the first step in capsid formation. The hairpin sequence was partially randomized to assess the importance of this structure element for the bacteriophage and to monitor alternative solutions that would evolve on the passaging of mutant phages. The evolutionary reconstruction of the operator failed in the majority of mutants. Instead, a poor imitation developed containing only some of the recognition signals for the coat protein. Three mutants were of particular interest in that they contained double nonsense codons in the lysis reading frame that runs through the operator hairpin. The simultaneous reversion of two stop codons into sense codons has a very low probability of occurring. Therefore the phage solved the problem by deleting the nonsense signals and, in fact, the complete operator, except for the initiation codon of the replicase gene. Several revertants were isolated with activities ranging from 1% to 20% of wild type. The operator, long thought to be a critical regulator, now appears to be a dispensable element. In addition, the results indicate how RNA viruses can be forced to step back to an attenuated form.     

Interleukin-6 gene promoter -174G/C polymorphism and insulin resistance: a pilot study.

BACKGROUND: The aim of this pilot study was to evaluate the relationship between interleukin-6 promoter -174G/C (IL-6 -174G/C) polymorphism and insulin resistance (IR) in obese patients with coronary heart disease (CHD). METHODS: Twenty obese male patients with CHD were selected from a larger database of patients (n=606). IL-6 -174G/C genotype was previously analysed and only homozygotes with the CC genotype (n=10) or GG genotype (n=10) were selected. IR was measured using the homeostasis model assessment for IR (HOMA-IR) method. RESULTS: Differences in age, body mass index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), hypertension, IL-6, C-reactive protein and HOMA-IR were not significant between the genotypes (p>0.05), but analysis of a homogeneity-of-slopes model showed that genotype had a significant influence on HOMA-IR (p=0.037), and the interaction between genotype and HDL-C had a pronounced tendency to affect HOMA-IR (p=0.058). Using multiple regression analysis, we found that HDL-C had a significant effect on HOMA-IR (p=0.023), and TG had a tendency to affect HOMA-IR (p=0.066) only in the CC genotype. CONCLUSIONS: Our data show that IL-6 -174G/C polymorphism may have a significant effect on IR. A comparison between the effects of various cardiovascular risk factors showed that HDL-C may have a significant effect on HOMA-IR in the CC genotype but not in the GG genotype. Further research is needed to test the preliminary results.     

C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease.

C-reactive protein (CRP) is an inflammatory marker associated with increased cardiovascular risk. Production of CRP is regulated by interleukin (IL)-1beta, IL-1 receptor antagonist and IL-6. In 160 patients with coronary heart disease (CHD) confirmed by angiography, we examined the relationship between CRP level and five polymorphisms in genes coding for these cytokines: IL-1B(-511), IL-1B(+3954), a variable number tandem repeat (VNTR) polymorphism in intron 2 of IL-1RN [IL-1RN(VNTR)], IL-6(-174) and IL-6(-572). CRP values were logarithmically normalized (log-CRP) for statistical calculations. In univariate analysis, carrier status for the IL-1B(+3954)T allele and IL-1RN(VNTR) allele 2 [IL-1RN(VNTR)*2] correlated with higher (P < 0.01) and lower (P < 0.05) log-CRP values, respectively. Among the potential confounding factors analysed, smoking, body mass index, total cholesterol (P < 0.05 for all) and diabetes (P = 0.056) were positively correlated with CRP level. After adjustment for non-genetic covariates, CRP levels remained significantly (P < 0.01) higher in carriers of IL-1B(+3954)T than in non-carriers: mean log-CRP (with 95% confidence interval) was 0.443 (0.311-0.574) for CT or TT genotypes compared with 0.240 (0.107-0.373) for the CC genotype, which corresponded to back-transformed CRP levels of 2.77 and 1.74 mg l(-1), respectively. Adjusted association was also significant for IL-1RN(VNTR)*2 (P < 0.01), with lower CRP levels in the presence of allele 2: the mean log-CRP value was 0.252 (0.115-0.388) for carriers and 0.421 (0.290-0.552) for non-carriers (CRP 1.79 and 2.64 mg l(-1), respectively). When alleles of both polymorphisms were entered into the model simultaneously, the association remained significant for IL-1B(+3954)T (P < 0.05), but not for IL-1RN(VNTR)*2. We conclude that IL-1B(+3954)T is associated with higher CRP levels in patients with CHD, and we found that this association was significant after adjustment for major risk factors. Our data also suggest a possible relationship of IL-1RN(VNTR)*2 with lower CRP levels in the same patients.     

Motor impairment predicts falls in specialized Alzheimer care units

We sought to identify clinical risk factors for falls in people with advanced Alzheimer disease (AD) in a prospective longitudinal observational study set in specialized AD care units. Forty-two patients with probable or possible AD were recruited. Age, sex, Mini-Mental Status Examination, Clinical Dementia Rating Scale, Neuropsychiatric Inventory/Nursing Home, Morse Fall Scale (MFS), modified Unified Parkinson's Rating Scale (mUPDRS), and gait parameters using a GAITRite Gold Walkway System with and without dual-task performance were examined. Time to a first fall was the primary outcome measure, and independent risk factors were identified. Participating subjects were old (non-fallers age, 82.3 +/- 6.7 years; fallers: 83.1 +/- 9.6 years; p = 0.76) and predominantly women (36 female/6 male). Fallers did not differ from non-fallers on any parameter except the MFS (non-fallers: 35.6 +/- 26.1; fallers: 54.4 +/- 29.8; p = 0.04), the UPDRS (non-fallers: 4.75 +/- 3.98; fallers: 7.61 +/- 4.3, p = 0.03) and cadence (steps per minute: non-fallers: 102.3 +/- 12.3; fallers: 91.7 +/- 16, p = 0.02). Fallers and non-fallers were equally affected by dual-task performance. The hazard ratios for MFS, UPDRS, and cadence were not affected by adjusting for age, sex, MMSE, or NPI scores. In conclusion, falls in advanced AD can be predicted using simple clinical measures of motor impairment or cadence. These measures may be useful for targeting interventions.