Predicting the Rate of Cognitive Decline in Alzheimer Disease: Data From the ICTUS Study.

BACKGROUND: Different rates of cognitive progression have been observed among Alzheimer disease (AD) patients. The present study aimed at evaluating whether the rate of cognitive worsening in AD may be predicted by widely available and easy-to-assess factors. METHODS: Mild to moderate AD patients were recruited in the ICTUS study. Multinomial logistic regression analysis was performed to measure the association between several sociodemographic and clinical variables and 3 different rates of cognitive decline defined by modifications (after 1 year of follow-up) of the Mini Mental State Examination (MMSE) score: (1) "slow" progression, as indicated by a decrease in the MMSE score ≤1 point; (2) "intermediate" progression, decrease in the MMSE score between 2 and 5 points; and (3) "rapid" progression, decrease in the MMSE score ≥6 points. RESULTS: A total of 1005 patients were considered for the present analyses. Overall, most of the study participants (52%) exhibited a slow cognitive course. Higher ADAS-Cog scores at baseline were significantly associated with both "intermediate" and "rapid" decline. Conversely, increasing age was negatively associated with "rapid" cognitive worsening. CONCLUSIONS: A slow progression of cognitive decline is common among AD patients. The influence of age and baseline cognitive impairment should always be carefully considered when designing AD trials and defining study populations.

Is nutrition important to postpone frailty?

PURPOSE OF REVIEW: The purpose of the present study is to provide an updated, systematic review of the recent literature on whether nutrition is important to postpone frailty. RECENT FINDINGS: A systematic review of recent literature (past 12 months) identified nine studies (eight of which using a cross-sectional design) exploring the relationship between nutrition and frailty. A single randomized controlled double-blind trial was published. However, being a pilot study, it was characterized by a relatively small sample size, short follow-up length (i.e., 6 months), and low statistical power. Notably, available evidence shows considerable variability in participants' selection and assessment methods, rendering difficult direct comparisons. Size effects or magnitude of associations across the different studies cannot also be determined. SUMMARY: There is a need for long-term, adequately powered, randomized controlled trials examining nutrition (alone and/or in combination with other appropriate interventions) as a means for postponing frailty in older persons.

Frailty: role of nutrition and exercise.

PURPOSE OF REVIEW: The scope of the current study is to provide an updated, comprehensive review of the recent literature (past 12 months), examining the role of nutrition and exercise on frailty. RECENT FINDINGS: Over the past 12 months, seven studies with different designs explored the relationship between nutrition and frailty, four examined the role of exercise on frailty, and only one study investigated the combination of the two interventions. The only study combining an exercise program with a nutritional consultation reported a short-term (3 months) improvement of the frailty status. Nevertheless, this study (a feasibility pilot trial) was characterized by a relatively small sample size, low response rates, and poor compliance. Notably, available evidence shows considerable variability in participants' selection, assessment methods, and outcomes of interest, so it is difficult to draw direct comparisons. Size effects or magnitude of associations across the different studies cannot also be determined. SUMMARY: The present findings suggest the need of long-term, adequately powered, randomized controlled trials testing nutrition, exercise or both interventions for the treatment of frailty in the elders. Such evidence will greatly support the future design of preventive strategies against disability in older persons.

Cross-sectional study examining the association between diet quality and the prevalence of anxiety and depression in UK undergraduate students.

The prevalence of mental health issues among UK undergraduate students is growing, and poor diet quality appears to be a risk factor for poor mental health although with limited research in this area. Therefore, the objective of this study was to examine the cross-sectional associations between diet quality and common mental disorders (CMD) such as depression and anxiety in UK undergraduate students. A cross-sectional survey consisting of demographic information and validated questionnaires (the Short-Form Food Frequency Questionnaire [SFFFQ] and the Hospital Anxiety and Depression Scale [HADS]) was conducted to measure diet quality and anxiety and depression in young adults in 44 UK-based universities. Multiple regression analysis adjusting for confounding factors was used to assess the associations between them. Undergraduate university students (n = 202, 67% female) with a mean age of 20.9 ± 3.6 years and a mean body mass index (n = 170) of 22.6 ± 3.2 kg/m2 took part in the study. Prevalence of anxiety was high, with 40% of the sample having an anxiety score in the severe range (≥12 points) while the prevalence of depression was lower, with 6% of the population having a depression score in the severe range (≥12 points). Diet quality was significantly higher for females than males (p = 0.034) and was poor for 38% of the sample, being more common in males compared to females, although not significantly so (43% and 36%, respectively). Diet quality was inversely associated with anxiety (ß = -0.427; p = 0.029) and was more likely to be associated with anxiety in females than males (ß = 0.743; p = 0.043). No significant relationship between diet quality and depression was found. Better self-reported health, father's qualification and smoking status were also associated with less anxiety and depression. This research supports other research suggesting that UK universities should explore whether the implementation of dietary interventions and improving the food environment would be a cost-effective option to reduce the high prevalence of anxiety among students.

Public beliefs and willingness to accept COVID-19 vaccines among adults in South-Western Nigeria: A cross-sectional study.

Background: Despite the government's and development partners' unmatched efforts to ensure that every eligible person receives vaccinations, there have been concerns about vaccine fear, government mistrust, vaccine hesitancy and rejection expressed by the public, as well as various conspiracy theories involving the COVID-19 vaccines. This study assessed the public beliefs and willingness to accept COVID-19 vaccines and related factors among residents of Ondo State, Nigeria. Methods: Using a convenience sample technique, a cross-sectional survey of the adult population was carried out in the months of February and March of 2022. Factors influencing beliefs and willingness to accept COVID-19 vaccines were found by using univariate and multivariate statistical analysis. Results: 306 out of 323 respondents completed the survey and were included in the final analysis. The respondents mean age was 28.16 ± 16.2 years. Although n = 223, 72.9% of respondents reported to have received at least one dose of COVID-19 vaccines, (n = 205) 67.0% believed COVID-19 vaccines to be effective. Among the individuals who had not yet had any COVID-19 vaccinations, 2.6% (n = 8) of respondents were willing to accept the vaccines, whereas 14.1% (n = 43) were unwilling. Respondents' beliefs about the efficacy of COVID-19 vaccines were influenced by their gender, occupation, religion and educational attainment (p < 0.005). Conclusion: The study revealed a good level of positive beliefs about the vaccine, which was mirrored in vaccination history. However, those who had not yet received the vaccine were unwilling to do so, opening the door for more aggressive risk communication to be able to alter the course of events. In addition to addressing additional COVID-19 vaccination myths, we advise policy-makers to develop communication strategies that emphasise the safety of the COVID-19 vaccine. It is advised that all relevant stakeholders be included in government COVID-19 vaccination programmes by sharing timely, transparent information that fosters accountability.

Altered mitochondrial microenvironment at the spotlight of musculoskeletal aging and Alzheimer's disease.

Emerging evidence has linked Alzheimer's disease (AD) onset with musculoskeletal aging via a muscle-brain crosstalk mediated by dysregulation of the mitochondrial microenvironment. This study investigated gene expression profiles from skeletal muscle tissues of older healthy adults to identify potential gene biomarkers whose dysregulated expression and protein interactome were involved in AD. Screening of the literature resulted in 12 relevant microarray datasets (GSE25941, GSE28392, GSE28422, GSE47881, GSE47969, GSE59880) in musculoskeletal aging and (GSE4757, GSE5281, GSE16759, GSE28146, GSE48350, GSE84422) in AD. Retrieved differentially expressed genes (DEGs) were used to construct two unique protein-protein interaction networks and clustering gene modules were identified. Overlapping module DEGs in the musculoskeletal aging and AD networks were ranked based on 11 topological algorithms and the five highest-ranked ones were considered as hub genes. The analysis revealed that the dysregulated expression of the mitochondrial microenvironment genes, NDUFAB1, UQCRC1, UQCRFS1, NDUFS3, and MRPL15, overlapped between both musculoskeletal aging and AD networks. Thus, these genes may have a potential role as markers of AD occurrence in musculoskeletal aging. Human studies are warranted to evaluate the functional role and prognostic value of these genes in aging populations with sarcopenia and AD.

Leptin up-regulates pro-inflammatory cytokines in discrete cells within mouse colon.

Dysregulation of leptin associated with obesity is implicated in obesity-related colon cancer, but mechanisms are elusive. Increased adiposity and elevated plasma leptin are associated with perturbed metabolism in colon and leptin receptors are expressed on colon epithelium. We hypothesise that obesity increases the sensitivity of the colon to cancer by disrupting leptin-regulated gene targets within colon tissues. PCR arrays were used to firstly identify leptin responsive genes and secondly to identify responses to leptin challenge in wild-type mice, or those lacking leptin (ob/ob). Leptin-regulated genes were localised in the colon using in situ hybridisation. IL6, IL1ß and CXCL1 were up-regulated by leptin and localised to discrete cells in gut epithelium, lamina propria, muscularis and at the peritoneal serosal surface. Leptin regulates pro-inflammatory genes such as IL6, IL1ß and CXCL1, and might increase the risk of colon cancer among obese individuals.

The prognostic value of body-mass index on mortality in older adults with dementia living in nursing homes.

BACKGROUND & AIMS: A protective effect of obesity on death has been reported in the context of various co-morbidities. We studied if the obesity paradox applied to nursing home (NH) older residents according to dementia status. METHODS: Prospective data from 3741 NH residents from France. All-cause mortality was the dependent measure. Subjects were categorized according with body mass index (BMI) as underweight, normal-weight, overweight, and obese. Dementia status was obtained from medical charts. Cox regressions were performed. RESULTS: There were 344 (9.2%) residents who were underweight, 1367 (43.8%) normal weight, 1069 (28.6%) overweight and 691 (18.5%) obese. 1083 (28.9%) people died during follow-up. In residents with dementia, mortality risk was reduced by almost half in overweight and obese people (HRs of 0.60 [0.48-0.76] and 0.53 [0.38-0.75], respectively; p < 0.001), and increased in underweight (HR = 1.65 [1.29-2.12]; p < 0.001) compared to normal-weight residents; moreover, each 1 kg/m2 increase in BMI decreased the risk of death by 12% and 9% in underweight and normal-weight subjects with dementia. For people without dementia, mortality risk was reduced in overweight and obese people (HRs of 0.80 [0.65-0.99], p = 0.042, and 0.77 [0.60-0.99], p = 0.044, respectively) compared to normal-weight; the 1-unit increase in BMI reduced the risk of death (23% reduction) only in underweight people. CONCLUSIONS: This study showed that the presence of dementia amplifies the obesity paradox in very old and functionally limited NH residents. Therefore, weight loss in NH residents, particularly in people with dementia, should be considered with extreme caution even for obese people.

Frailty Index and Incident Mortality, Hospitalization, and Institutionalization in Alzheimer's Disease: Data From the ICTUS Study.

BACKGROUND: The identification of an objective evaluation of frailty capable of predicting adverse outcomes in Alzheimer's disease is increasingly discussed. The purpose of this study was to investigate whether the Frailty Index (FI) predicts hospitalization, institutionalization, and mortality in Alzheimer's disease patients. METHODS: A prospective multicenter cohort study (follow-up = 2 years) that included 1,191 participants with Alzheimer's disease was carried out. The outcomes of interest were incident hospitalization, institutionalization, and mortality. The FI was calculated as the ratio of actual to thirty potential deficits, that is, deficits presented by the participant divided by 30. Severity of dementia was assessed using the Clinical Dementia Rating score. Cox proportional hazard models were performed. RESULTS: Mean age of the study sample was 76.2 (SD = 7.6) years. A quadratic relationship of the FI with age was reported at baseline (R (2) = .045, p < .001). The FI showed a statistically significant association with mortality (age- and gender-adjusted hazard ratio [HR] = 1.019, 95% confidence interval [CI] = 1.002-1.037, p = .031) and hospitalization (age- and gender-adjusted HR = 1.017, 95% CI = 1.006-1.029, p = .004) and a borderline significance with institutionalization. When the Clinical Dementia Rating score was simultaneously included in the age- and gender-adjusted models, the FI confirmed its predictive capacity for hospitalization (HR = 1.019, 95% CI = 1.006-1.032, p = .004), whereas the Clinical Dementia Rating score was the strongest predictor for mortality (HR = 1.922, 95% CI = 1.256-2.941, p = .003) and institutionalization (HR = 1.955, 95%CI = 1.427-2.679, p < .001). CONCLUSIONS: The FI is a robust predictor of adverse outcomes even after the stage of the underlying dementia is considered. Future work should evaluate the clinical implementation of the FI in the assessment of demented individuals in order to improve the personalization of care.

Frailty Index and Cognitive Decline in Alzheimer's Disease: Data from the Impact of Cholinergic Treatment USe Study.

OBJECTIVES: To determine whether the Frailty Index (FI) was associated with short-term cognitive decline (according to changes in Mini Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores at 1-year follow-up) in individuals with Alzheimer's disease (AD). DESIGN: Prospective cohort study. SETTING: Impact of Cholinergic Treatment USe study. PARTICIPANTS: Individuals with mild-to-moderate AD (N = 973). MEASUREMENTS: Severity of dementia was assessed using the Clinical Dementia Rating (CDR). FI was calculated as the ratio of actual to potential deficits (deficits present divided by 30). Linear regression analyses were performed and stratified according to severity of dementia. RESULTS: A 1-unit (0.033 points) increase in FI corresponded to significant and clinically relevant cognitive decline, after adjustments for age, sex, and years of education (0.63-4.63 points on the MMSE, P = .01; 2.87-11.1 points on the ADAS-Cog, P = .001) after 1 year of follow-up. Differences in changes in MMSE and ADAS-Cog scores between nonfrail and frail individuals were 0.67 and 1.6 points, respectively. Although statistically significant, the clinical relevance of this finding remains to be further investigated. CONCLUSION: The FI may be a promising instrument for the assessment of the vulnerability of individuals with AD. Its implementation in clinical practice may support clinical decisions by identifying individuals at high risk of negative outcomes, specifically, short-term cognitive decline.

Frailty Index and Quality of Life in Nursing Home Residents: Results From INCUR Study.

BACKGROUND: Frailty is a common clinical syndrome in older adults that carries an increased risk for poor health outcomes. The aim of this study was to examine the relationship between frailty and health-related Quality of Life (QoL) in older nursing home patients. METHODS: The study sample consisted of 590 patients aged 65 years or older. QoL was measured with the Visual Analogue Scale. Frailty was assessed using the Frailty Index as proposed by Rockwood and colleagues. RESULTS: Mean age of the participants was 85.9 (standard deviation [SD] 7.6) years, with 73.6% being female. The mean Frailty Index was 0.40 (SD 0.07) and the mean value of QoL was 67.4 out of 100 (SD 25.9). Before and after adjusting for age, and stratification for sociodemographic, and health-related variables, no significant associations between frailty and QoL were reported. CONCLUSION: In our study, the Frailty Index was not associated with QoL in nursing home residents.

Dietary Magnesium Is Positively Associated With Skeletal Muscle Power and Indices of Muscle Mass and May Attenuate the Association Between Circulating C-Reactive Protein and Muscle Mass in Women.

Age-related loss of skeletal muscle mass and strength are risk factors for sarcopenia, osteoporosis, falls, fractures, frailty, and mortality. Dietary magnesium (Mg) could play a role in prevention of age-related loss of skeletal muscle mass, power, and strength directly through physiological mechanisms or indirectly through an impact on chronic low-grade inflammation, itself a risk factor for loss of skeletal muscle mass and strength. In a cross-sectional study of 2570 women aged 18 to 79 years, we examined associations between intakes of Mg, estimated using a food-frequency questionnaire (FFQ), dual-energy X-ray absorptiometry (DXA)-derived measures of muscle mass (fat-free mass as a percentage of body weight [FFM%], fat-free mass index [FFMI, kg/m(2)]), leg explosive power (LEP), and grip strength (n = 949 only). We also examined associations between circulating hs-CRP (C-reactive protein) and muscle mass and LEP, and explored the potential attenuation of these relationships by Mg. We compared our findings with those of age and protein intake. Endpoints were calculated by quintile of Mg and adjusted for relevant confounders. Significant positive associations were found between a higher Mg and indices of skeletal muscle mass and LEP, and also with hs-CRP, after adjustment for covariates. Contrasting extreme quintiles of Mg intake showed differences of 2.6% for FFM% (p trend < 0.001), 0.4 kg/m(2) for FFMI (p trend = 0.005), and 19.6 watts/kg for LEP (p trend < 0.001). Compared with protein, these positive associations were 7 times greater for FFM% and 2.5 times greater for LEP. We also found that higher hs-CRP was negatively associated with skeletal muscle mass and, in statistical modeling, that a higher dietary Mg attenuated this negative relationship by 6.5%, with greater attenuation in women older than 50 years. No association was found between Mg and grip strength. Our results suggest that dietary magnesium may aid conservation of age-related loss of skeletal muscle mass and power in women of all ages.

Refining Mild-to-Moderate Alzheimer Disease Screening: A Tool for Clinicians.

OBJECTIVES: Recent evidence suggests that a substantial minority of people clinically diagnosed with probable Alzheimer disease (AD) in fact do not fulfill the neuropathological criteria for the disease. A clinical hallmark of these phenocopies of AD is that these individuals tend to remain cognitively stable for extended periods of time, in contrast to their peers with confirmed AD who show a progressive decline. We aimed to examine the prevalence of patients clinically diagnosed with mild-to-moderate AD who do not experience the expected clinically significant cognitive decline and identify markers easily available in routine medical practice predictive of a stable cognitive prognosis in this population. DESIGN: Data were obtained from two independent, longitudinal, observational multicenter studies in patients with mild-to-moderate AD. SETTING: The two studies were the European "Impact of Cholinergic Treatment Use" (ICTUS) and the French "REseau sur la maladie d'Alzheimer FRançais" (REAL.FR). PARTICIPANTS: We used prospective data of 756 patients enrolled in ICTUS and 340 enrolled in REAL.FR. MEASUREMENTS: A prediction rule of cognitive decline was derived on ICTUS using classification and regression tree analysis and then cross-validated on REAL.FR. A range of demographic, clinical and cognitive variables were tested as predictor variables. RESULTS: Overall, 27.9% of patients in ICTUS and 20.9% in REAL.FR did not decline over 2 years. We identified optimized cut-points on the verbal memory items of the Alzheimer Disease Assessment Scale-Cognitive Subscale capable of classifying patients at baseline into those who went on to decline and those who remained stable or improved over the duration of the trial. CONCLUSION: The application of this simple rule would allow the identification of dementia cases where a more detailed differential diagnostic examination (eg, with biomarkers) is warranted. These findings are promising toward the refinement of AD screening in the clinic. For a further optimization of our classification rule, we encourage others to use our methodological approach on other episodic memory assessment tools designed to detect even small cognitive changes in patients with AD.

Frailty Index and Mortality in Nursing Home Residents in France: Results From the INCUR Study.

OBJECTIVE: The objective of this study was to examine whether the capacity of an age-related deficit accumulation index (the so-called Frailty Index [FI] proposed by Rockwood) to predict mortality in a nursing home population. DESIGN, SETTING, AND PARTICIPANTS: Data are from a longitudinal cohort study (ie, the Incidence of pNeumonia and related ConseqUences in nursing home Residents [INCUR]) of 773 older persons (74.4% women) living in 13 French nursing homes. MEASUREMENTS: The FI was computed as the ratio between actual and 30 potential deficits the participant might have presented at the baseline visit (range between 0 [no deficit] and 1 [30 deficits]). Death events were monitored and detected over a 12-month follow-up. The risk of death was estimated using Cox proportional hazards models. RESULTS: Mean age of participants was 86.2 (SD 7.5) years, with a mean FI of 0.35 (SD 0.11). At the end of the follow-up, 135 (17.4%) death events were recorded. A positive association between the FI and mortality (per 0.01 FI increment: age- and gender-adjusted hazard ratio 1.018, 95% confidence interval 1.002-1.035, P = .03) was reported. The use of the traditional 0.25 cut-point for detecting the frailty status is inadequate in this population. CONCLUSION: The FI is able to predict mortality even in very old and complex elders, such as nursing home residents.

Effects of Gingko biloba supplementation in Alzheimer's disease patients receiving cholinesterase inhibitors: data from the ICTUS study.

Ginkgo biloba (Gb) is currently the most investigated and adopted herbal remedy for cognitive disorders and Alzheimer's disease (AD). Nevertheless, its efficacy in the prevention and treatment of dementia still remains controversial. Specifically, the added effects of Gb in subjects already receiving "conventional" anti-dementia treatments have been to date very scarcely investigated. We evaluated whether the use of Gb is associated with additional cognitive and functional benefit in AD patients already in treatment with cholinesterase inhibitors (ChEIs). Data are from mild to moderate AD patients under ChEI treatment recruited in the Impact of Cholinergic Treatment USe (ICTUS) study. Mixed model analyses were performed to measure six-monthly modifications in the Mini Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score, and the Activities of Daily Living (ADL) scale over a follow-up of 1 year according to the additional Gb supplementation. A total of 828 subjects were considered for the present analyses. Significantly different modifications at the MMSE score over the 12-month follow-up were reported between patients on combined therapy compared to those only taking ChEIs. On the contrary, the modification of the ADAS-Cog score between the two groups did not show statistically significant differences, although similar trends were noticed. No significant modifications of the two adopted outcome measures were observed at the mid-term 6-month evaluation. The modifications over time of the ADL score did not show statistically significant differences between the two groups of interest. Our findings suggest that Gb may provide some added cognitive benefits in AD patients already under ChEIs treatment. The clinical meaningfulness of such effects remains to be confirmed and clarified.

Nutritional status and the incidence of pneumonia in nursing home residents: results from the INCUR study.

OBJECTIVES: To examine the predictive value of the Mini Nutritional Assessment-short form (MNA-SF) and its individual items on the incidence of pneumonia. DESIGN: Prospective observational cohort study over 1-year of follow-up. PARTICIPANTS: A total of 773 older persons (74.4% women) living in 13 French nursing homes from the Incidence of pNeumonia and related ConseqUences in nursing home Residents (INCUR) study. MEASUREMENTS: Nutritional status was assessed using the MNA-SF questionnaire at baseline. Diagnosis of pneumonia was based on clinical conditions retrieved from a medical chart. Cox proportional hazard models were applied to test whether the MNA-SF score and its single components predict pneumonia events over 1 year of follow-up. RESULTS: After 1 year of follow-up, 160 (21%) incident cases of pneumonia were recorded. Mean age of participants was 86.2 (SD 7.5) years. Mean MNA-SF score was 9.8 (SD 2.4), with more than half of the participants (58.7%) being at risk of malnutrition (8-11 points). The total MNA-SF score and its categories did not predict the studied outcome. However, a single component of the MNA-SF score, specifically decreased mobility, was a significant risk factor for pneumonia (hazard ratio 2.289; 95% confidence interval 1.357-3.860; P = .002), independently of potential confounders. CONCLUSIONS: The total MNA-SF score did not predict the incidence of pneumonia. However, decreased mobility was a significant risk factor, implying that individual components of the MNA-SF should be more carefully explored to verify whether they might be used for detecting specific declines of the health status in nursing home residents, thus potentially improving the risk profile estimation of such a complex population.