Rapid cognitive decline in Alzheimer's disease: a literature review.

BACKGROUND: The rate of cognitive decline in Alzheimer's disease (AD) varies considerably between individuals. Predicting rapid cognitive decline might help clinicians provide prognostic information, select subjects for trial intervention and/or reduce costs. METHODS: PubMed and PsycINFO were searched for all the English written studies published until the end of 2010 on rapid cognitive decline in AD and factors associated with it. RESULTS: More than 300 individual articles were retrieved. We selected 82 relevant studies. The main findings of these papers are that younger, more educated and more impaired patients are more likely to show rapid cognitive decline. ApoE alleles seem not to modify the velocity of clinical progression of dementia, or at most could have a very small effect. No inference can be made for all the other variables analysed. CONCLUSIONS: There are many studies on rapid cognitive decline. Results are heterogeneous and often contradictory. No reliable conclusions about factors that may be associated with rapid cognitive decline can yet be drawn.

Determinants of recourse to hospital treatment in the elderly.

BACKGROUND: All over Europe, an increased use of public health services has been noticed, particularly referring to access and hospitalization among elderly in the emergency department (ED). METHODS: Prospective study at a university teaching hospital in Turin, northern Italy, recruiting subjects aged >65 years consecutively attending the medical ED during 1 month. Demography, functional and cognitive status, comorbidity, severity of acute critical illness, previous ED accesses and hospitalization, diagnosis and other relevant data for ED admission and hospitalization were considered. RESULTS: Data were collected for 1632 patients (average age 77.6 years), 89% of the 1834 older subjects who attended the ED during the study period (29.3% of the patients attending the ED). Six hundred and fifty older subjects were admitted to the hospital (62.2% of the hospital admissions). Severity of acute critical illness, presence of chronic obstructive pulmonary disease and heart failure, a high number of drugs being taken, functional dependence and advanced age were independently associated with hospital admission. One-third of the patients appeared to be frequent users of health services with more than two visits/admissions. Higher comorbidity, partial or complete functional dependence, chronic diseases (arrhythmia, pulmonary neoplasm, diseases of the large intestine) and politherapy were associated either with frequent use of the ED and multiple admissions. CONCLUSIONS: Elderly account for a high proportion of hospitalizations, mainly determined by critical health conditions, advanced age and functional dependence. Poor health conditions (high comorbidity and presence of chronic multi-organ diseases), functional dependence but not critical social factors were the main determinants of multiple hospital admissions.

Predictors of rapid cognitive decline in Alzheimer's disease: results from the Australian imaging, biomarkers and lifestyle (AIBL) study of ageing.

BACKGROUND: The AIBL study, which commenced in November 2006, is a two-center prospective study of a cohort of 1112 volunteers aged 60+. The cohort includes 211 patients meeting NINCDS-ADRDA criteria for Alzheimer's disease (AD) (180 probable and 31 possible). We aimed to identify factors associated with rapid cognitive decline over 18 months in this cohort of AD patients. METHODS: We defined rapid cognitive decline as a drop of 6 points or more on the Mini-Mental State Examination (MMSE) between baseline and 18-month follow-up. Analyses were also conducted with a threshold of 4, 5, 7 and 8 points, as well as with and without subjects who had died or were too severely affected to be interviewed at 18 months and after, both including and excluding subjects whose AD diagnosis was "possible" AD. We sought correlations between rapid cognitive decline and demographic, clinical and biological variables. RESULTS: Of the 211 AD patients recruited at baseline, we had available data for 156 (73.9%) patients at 18 months. Fifty-one patients were considered rapid cognitive decliners (32.7%). A higher Clinical Dementia Rating scale (CDR) and higher CDR "sum of boxes" score at baseline were the major predictors of rapid cognitive decline in this population. Furthermore, using logistic regression model analysis, patients treated with a cholinesterase inhibitor (CheI) had a higher risk of being rapid cognitive decliners, as did males and those of younger age. CONCLUSIONS: Almost one third of patients satisfying established research criteria for AD experienced rapid cognitive decline. Worse baseline functional and cognitive status and treatment with a CheI were the major factors associated with rapid cognitive decline over 18 months in this population.

Implications of routinely measuring Ankle-Brachial Index (ABI) among patients attending at a Lipid Clinic.

BACKGROUND: Low (< or = 90) Ankle Brachial Index (ABI) values identify patients at high risk for cardiovascular (CV) disease and mortality. Implications for CV risk classification from routinely measuring ABI in the context of a Lipid Clinic have not been fully investigated. We aimed to evaluate whether and to what extent routine ABI determination on top of conventional risk prediction models may modify CV risk classification. METHODS: Consecutive asymptomatic non-diabetic individuals free from previous CV events attending for a first visit at a Lipid Clinic underwent routine ABI determination and conventional CV risk classification according either to national CUORE model (including age, gender, smoking, total and high density lipoprotein cholesterol, systolic blood pressure and current use of blood pressure lowering drugs) and SCORE model for low risk countries. RESULTS: In the overall sample (320 subjects, mean age 64.8 years) 77 subjects (24.1%) were found to have low ABI value. Forty-two of 250 subjects (16.8%) and 47 of 215 individuals (21.3%) at low or moderate risk according to the CUORE and SCORE models, respectively, were found to have low ABI values, and should be reclassified at high risk. CONCLUSION: In a series of consecutive asymptomatic individuals in a Lipid Clinic, we observed a high prevalence of low ABI values among subjects deemed at low or moderate risk on conventional prediction models, leading to CV high-risk reclassification of roughly one fifth of patients. These findings reinforce recommendations for routine determination of ABI at least within referral primary prevention settings.

Efficacy of oxycodone/acetaminophen and codeine/acetaminophen vs. conventional therapy in elderly women with persistent, moderate to severe osteoarthritis-related pain.

We aimed to evaluate the efficacy and safety of oxycodone/acetaminophen (O/A) and codeine/acetaminophen (C/A) vs. conventional therapy (CT) without opioids in older women suffering from osteoarthritis (OA)-related pain, sub-optimally responsive to prior conventional treatments. We performed a 6 week, randomized, single blind, controlled study in three nursing homes. We enrolled 154 women with painful OA. They were assigned to treatment with O/A (n=52) and C/A (n=52) vs. CT (n=50). We evaluated at baseline and at week 6: average pain in the last week (mean pain, MeP), pain at rest (RP), pain in movement (MP) (numeric rating scale, NRS); depressive symptoms (Beck Depression Inventory-II, BDI-II); functional status (activities of daily living, ADL) and cognitive status (mini mental state evaluation, MMSE). We considered the adverse events (AEs) in the study period. At week 6, MeP, RP and MP were significantly reduced in all three groups (p<0.001); compared to CT, O/A and C/A were associated with greater reductions in MeP (p<0.001 and p=0.004, respectively), in RP (p=0.028 and p=0.032, respectively) in MP (p<0.001 and p=0.002, respectively) and with significant improvement in BDI-II score (p=0.05 and p=0.04, respectively) and ADL value (p=0.04 and p=0.05, respectively). AE rates did not differ between groups.

White-coat effect among older patients with suspected cognitive impairment: prevalence and clinical implications.

OBJECTIVES: To evaluate the prevalence of white-coat effect (WCE), and its association with individual anxiety and insight of disease, among older patients evaluated for suspected cognitive impairment. METHODS: This prospective cohort study, conducted in an Alzheimer Evaluation Unit, involved patients aged 55 years or older with suspected cognitive impairment. WCE was defined as a difference of at least 20 mmHg in systolic or 10 mmHg in diastolic blood pressure (BP) measured either by a physician during the visit or by a nurse (before and after the visit), compared with home self-blood pressure measurement (SBPM). Severity of cognitive impairment was evaluated through the Mini-Mental State Examination (MMSE); the Clinical Insight Rating Scale (CIR) and the Guidelines for the Rating for Awareness Deficits (GRAD) were used to evaluate the subject's insight; anxiety disorder was evaluated using the seven-question Generalized Anxiety Disorder scale (GAD-7). RESULTS: Among 273 subjects, prevalence of WCE was 52%, 32.6% and 30.4%, according to physician and nurse BP measurements, respectively (p = 0.000). Prevalence of WCE did not differ between patients diagnosed with and without dementia, but was higher among patients with than in those without anxiety disorder (70.7% vs 38.2%, p = 0.000). Positive relations were observed between severity of anxiety and insight of disease, which were both inversely related with severity of cognitive impairment. CONCLUSIONS: WCE is extremely common and is correlated to individual anxiety and insight of disease among older outpatients with suspected cognitive impairment; overestimation of hypertension severity might lead to unnecessary drug treatment and greater health costs in this setting.

High-sensitivity C-reactive protein is not independently associated with peripheral subclinical atherosclerosis.

OBJECTIVE: This study investigated whether high-sensitivity C-reactive protein (hs-CRP) levels are independently associated with subclinical peripheral atherosclerosis. METHODS: Clinical variables, cardiovascular (CV) risk factors, 10-year CV risk, the ankle-brachial Index (ABI), and the carotid intima-media thickness (cIMT) were determined in a sample of consecutive subjects free from previous CV disease, admitted for a first visit at a lipid clinic. RESULTS: In the overall sample (320 subjects, mean age 63 years, 35.8% men), hs-CRP levels were associated with major CV risk factors, 10-year CV risk, lower ABI, and higher cIMT values. In a logistic model, after adjustment for significant covariates, the associations of hs-CRP levels with ABI and cIMT were no longer statistically significant. CONCLUSIONS: Among asymptomatic, moderate- to-high CV risk subjects, hs-CRP levels were associated with severity of peripheral atherosclerosis, but these associations were not independent of traditional CV risk factors, suggesting a limited predictive role of hs-CRP for subclinical atherosclerosis.

Metabolic syndrome in older subjects: coincidence or clustering?

The prevalence of the metabolic syndrome (MS) increases with advancing age. However, aging per se is associated with increased prevalence of most of the abnormalities contributing to the MS. Whether MS in older people consistently identifies a true pathophysiological entity or a casual aggregation of aging-associated metabolic abnormalities, remains to be fully elucidated. In the present study, we aimed to evaluate whether in older subjects the aggregation of metabolic components of the MS, as defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), is consistent with a single latent variable. Age, waist circumference, systolic and diastolic blood pressure, metabolic variables were determined in 152 older (>70 years), non-diabetic, healthy men. Cronbach alpha was used to assess the internal consistency of the components contributing to the MS. Structural equation modeling, using the Normed Fit Index (NFI), the Root Mean Square Error of Approximation (RMSEA), the Comparative Fit Index (CFI), and the Tucker-Lewis Index (TLI) was used to assess the fit to a model with a single latent variable. The Cronbach alpha test showed low internal consistency among the metabolic variables (alpha=0.31). The calculated chi(2) values were 28.31 and 32.52 for model entering hypertension as dichotomous variable and for model entering blood pressure values, respectively, both expressing low fit to a model with a single latent variable. In both models, CFI (0.41 and 0.55), NFI (0.59 and 0.55), RMSEA (0.25 and 0.22) and TLI (-0.31 and -0.12) scores showed a low fit of the metabolic alterations to a single latent variable. These findings suggest caution in making diagnosis of MS at older ages, since metabolic and cardiovascular abnormalities being per se extremely common in elderly people, do not appear to cluster together under a single common factor.

Clinical implications of white-coat effect among patients attending at a lipid clinic.

We evaluated clinical implications of the white-coat effect (WCE) in cardiovascular (CV) risk stratification in the primary prevention setting of a Lipid Clinic. We compared home self blood pressure measurement (SBPM) with office blood pressure (BP) readings and BP measured by a nurse before and after the visit on consecutive subjects, free of previous CV diseases, attending at a Lipid Clinic for a first visit. Additionally, we evaluated whether and to what extent the difference between these measurements affect the 10-year cardiovascular risk calculated according to current guidelines. Mean home self-measured systolic and diastolic BP values were significantly lower than physician's and nurse's readings (p=0.000). A WCE was observed in 60.3% of patients during the physician's visit, and in 33.9% and 36.6% of nurse's measurements before and after visit, respectively. Compared with computation of SBPM, inclusion in risk predictive model of systolic BP values obtained by physician and nurse (before or after visit) resulted in significantly higher calculated CV risk (p=0.000) and in a higher risk-class allocation in 16.5%, 8.5% and 9.4% of patients, respectively (p=0.000). Our findings show that among patients attending at a Lipid Clinic there is a high prevalence of WCE, which is roughly halved when nurse's BP measurements were considered. Nurse's BP measurements before or after the doctor's visit may reduce, but not eliminate at all, the clinic overestimation of BP. The WCE associated with physician's office visit carries a substantial probability of 10-year CV risk overestimation in the primary prevention setting.