Unfairness and the social gradient of metabolic syndrome in the Whitehall II Study

OBJECTIVES: Little work has investigated the relationship between unfairness and risk factors for heart disease. We examine the role of unfairness in predicting the metabolic syndrome and explaining the social gradient of the metabolic syndrome. METHODS: The design is a prospective study with an average follow-up of 5.8 years. Participants were 4128 males and 1715 females of 20 civil service departments in London (Whitehall II study). Sociodemographics, unfairness, employment grade, behavioral risk factors, and other psychosocial factors were measured at baseline (Phase 3, 1991-1993). Waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, fasting glucose, and hypertension were used to define metabolic syndrome at follow-up (Phase 5, 1997-2000), according to the National Cholesterol Education Program/Adult Treatment Panel III guidelines. RESULTS: Unfairness is positively associated with waist circumference, hypertension, triglycerides, and fasting glucose and negatively associated with serum HDL cholesterol. High levels of unfairness are also associated with the metabolic syndrome [odds ratio (OR)=1.72, 95% CI=1.31-2.25], after adjustment for age and gender. After additional adjustment for employment grade, behavioral risk factors, and other psychosocial factors, the relationship between high unfairness and metabolic syndrome weakened but remained significant (OR=1.37, 95% CI=1.00-1.93). When adjusting for unfairness, the social gradient of metabolic syndrome was reduced by approximately 10%. CONCLUSION: Unfairness may be a risk factor for the metabolic syndrome and its components. Future research is needed to study the biological mechanisms linking unfairness and the metabolic syndrome.     

Conversion of amnestic Mild Cognitive Impairment to dementia of Alzheimer type is independent to memory deterioration

BACKGROUND: Mild Cognitive Impairment defines a transitional stage between normal ageing and dementia, and reflects the clinical situation where a person has memory complaints and objective evidence of cognitive impairment but no evidence of dementia. To plan the care of patients with MCI, it is important to predict as accurately as possible potential risk factors modulating the conversion to AD. AIM: To investigate the risk factors associated of conversion to dementia of Alzheimer type (AD) for subjects with amnestic Mild Cognitive Impairment (aMCI). METHODS AND MATERIALS: One hundred nineteen subjects consecutively recruited who met the operational criteria for aMCI (with or without deficits in other cognitive domains). They underwent multidimensional assessment and a neuropsychological battery at baseline and at follow-up, after 1 year. Diagnosis for dementia was based on a deficit in two or more cognitive domains severe enough to affect the participant functional abilities. Subjects converted to AD over time were classified as Demented; subjects that remained unchanged, or became cognitively normal during follow-up, were defined as Stable. RESULTS: Demented MCI (N = 40; 33.6%) were older (mean age 73.5 +/- 8.5 vs. 69.2 +/- 7.0; p = 0.006) when compared to Stable (N = 79; 66.4) and their global cognitive performances, at baseline, were more compromised when assessed by ADAS-Cog (mean score 10.7 +/- 3.9 vs 6.7 +/- 3.4; p = .000) and by MMSE (mean score 26.1 +/- 1.9 vs. 27.3 +/- 1.8; p = 0.002). Demented were similarly compromised in basic activities of daily living (BADL mean 0.2 +/- 0.4 vs 0.1 +/- 0.3 functions lost; p = NS) but more compromised on instrumental daily functions (IADL mean 0.7 +/- 0.8 vs. 0.1 +/- 0.5 functions lost; p = 0.001). The presence of white matter lesions (WML) on CT or MRI was more pronounced in Demented group (p = 0.02). After 1 year; Demented worsened on phonemic verbal fluency (PFL) (p = 0.009), Raven's coloured matrices (p = 0.003), Trail Making test A and B (p = 0.008 and p = 0.007 respectively) and in Instrumental Activities of Daily Living (IADL) (p =0 .000) respect to Stable. Logistic regression analysis revealed that ADAS-Cog basal score, Trail Making B, IADL but not memory deterioration were significantly associated to the conversion to AD. CONCLUSIONS: In subjects with aMCI poor global cognitive performance at baseline, the worsening on executive functions and on functional status but not the worsening on memory functions are independently associated with the conversion to dementia of Alzheimer type at 1 year, follow-up.     

Estrogen receptor 1 polymorphisms and risk of cognitive impairment in older women.

BACKGROUND: Several genes associated with sporadic Alzheimer's disease have been identified; however, approximately 50% of genetic factors remain unidentified. We investigated whether estrogen receptor 1 (ESR1) polymorphisms are associated with risk of developing cognitive impairment in older women. METHODS: A total of 2625 women > or = 65 years of age completed a modified Mini-Mental Status Exam (mMMSE) at baseline and at 6-8 years of follow-up. We defined cognitive impairment as a mMMSE decline of > or = 3 points, follow-up score < or = 20, or a history of physician-diagnosed dementia. The ESR1 polymorphisms, PvuII (P or p) and XbaI (X or x), were coded so that the capital letter signifies the absence of the restriction site. RESULTS: Women with a p allele had a greater age, education, and baseline-score adjusted decline in mMMSE (for PP, Pp, and pp, respectively:.6 +/-.1,.8 +/-.1, and.9 +/-.1 points, p for trend =.01); women with at least one x allele also had greater score decline (XX, Xx, and xx:.7 +/-.1,.7 +/-.1, and.9 +/-.1 points, p for trend =.02). Six percent (n = 166) of the women developed cognitive impairment. Compared to those who did not develop impairment, more women who developed cognitive impairment had a p allele (62% vs. 56%, p =.03; adjusted odds ration (OR) = 1.33; 95% confidence interval [CI], 1.03-1.72) or an x allele (70% vs. 64%, p =.03; adjusted OR = 1.38; 95% CI, 1.06-1.81). There was no interaction with current estrogen use, or with serum estradiol level and ESR1 polymorphisms (p >.10). CONCLUSIONS: Estrogen receptor 1 polymorphisms are associated with risk of developing cognitive impairment. More research is needed to determine the mechanism whereby ESR1 polymorphisms or linked genes influence cognitive function in older women.     

APOE genotype,memory test performance,and the risk of Alzheimer's disease in the Canadian Study of Health and Aging

OBJECTIVES: This study examined the relation between two risks for Alzheimer's disease (AD): the apolipoprotein (APOE) epsilon4 allele and poor memory test performance. METHODS: In the Canadian Study of Health and Aging (CSHA), a 5-year longitudinal population-based study that screened and followed over 10,000 participants, 2,914 had an initial clinical assessment and 1,624 had APOE genotype testing. All participants were categorized as having no cognitive impairment, cognitive impairment but no dementia, or dementia at both baseline and follow-up. We examined those (n = 209) with a complete neuropsychological assessment at baseline and no evidence of cognitive impairment who had either APOE epsilon3/epsilon3 or epsilon3/epsilon4 genotypes and who had a clinical consensus diagnosis of either no cognitive impairment or AD at follow-up. Delayed free recall memory was evaluated at CSHA-1 with the Buschke Cued Recall Test (BCRT). RESULTS: The risk of AD at follow-up was increased for participants with an APOE epsilon3/epsilon4 genotype when memory test performance was not considered, but logistic regression demonstrated that a model which also considered baseline memory test performance was more predictive of AD. In the more complete model, reduced BCRT free recall scores were associated with an increased risk of AD, whereas the risk associated with the APOE epsilon3/epsilon4 genotype was no longer significant. CONCLUSIONS: For those with no evidence of cognitive impairment, drawn from a population-based sample of elderly persons, the APOE epsilon3/epsilon4 genotype was only associated with an increased risk of AD after 5 years if their memory test performance was relatively poor at baseline. Regardless of the APOE genotype, and in the absence of clinical evidence of cognitive impairment, reduced scores on a test of delayed free recall at baseline was associated with an increased risk of AD after 5 years.     

Mild cognitive impairment in different functional domains and incident Alzheimer's disease

BACKGROUND: Little is known about factors that predict transition from mild cognitive impairment to Alzheimer's disease (AD). OBJECTIVE: To examine the relation of impairment in different cognitive systems to risk of developing AD in persons with mild cognitive impairment. METHODS: Participants are 218 older Catholic clergy members from the Religious Orders Study. At baseline, they met criteria for mild cognitive impairment based on a uniform clinical evaluation that included detailed cognitive testing. Evaluations were repeated annually for up to 10 years. Analyses were controlled for age, sex, and education. RESULTS: Eighty two persons (37.6%) developed AD. In separate analyses, episodic memory, semantic memory, working memory, and perceptual speed, but not visuospatial ability, were associated with risk of AD, but when analysed together only episodic memory and perceptual speed were associated with AD incidence, with the effect for episodic memory especially strong. Overall, those with impaired episodic memory were more than twice as likely to develop AD as those with impairment in other cognitive domains (relative risk (RR) = 2.45; 95% confidence interval (CI): 1.53 to 3.92), and they experienced more rapid cognitive decline. Lower episodic memory performance was associated with increased risk of AD throughout the observation period, whereas impairment in other cognitive domains was primarily associated with risk during the following year but not thereafter. CONCLUSION: Among persons with mild cognitive impairment, episodic memory impairment is associated with a substantial and persistent elevation in risk of developing AD compared to impairment in other cognitive systems.     

Impact of cardiovascular risk factors on cognitive function: The Tromsø study

Background and purpose: The role of cardiovascular risk factors in the pathogenesis of cognitive impairment and dementia remains still unclear. We examined the impact of cardiovascular risk factors on cognitive function in a large longitudinal population study. Methods: Subjects were 5033 stroke‐free men and women who participated in a longitudinal population‐based study. Cardiovascular risk factors were measured at baseline, and cognitive function was assessed after 7 years of follow‐up with verbal memory test, digit‐symbol coding test, and tapping test. Results: Diabetes, systolic blood pressure, and current smoking were independently associated with lower cognitive test results in men and women. Low physical activity was independently associated with lower scores in women. We found no consistent association between total‐cholesterol, HDL‐cholesterol, coronary heart disease or BMI, and cognitive test results. Conclusions: Diabetes, smoking, hypertension, and low physical activity were associated with lower cognitive test results. The study suggests that these modifiable risk factors should be emphasized in the prevention of cognitive decline.     

Risk Aversion and Alzheimer Disease in Old Age

Objective: To test the hypothesis that late-life risk aversion is partly a prodromal sign of dementia. Methods: The authors’ design was a longitudinal clinical-pathologic cohort study. The setting included participants’ residences in the Chicago area, and a total of 874 older persons without dementia were enrolled. At baseline, risk aversion was assessed with questions involving choices between certain smaller rewards and uncertain larger rewards. At annual intervals thereafter, participants underwent evaluations that included cognitive testing and diagnosis of mild cognitive impairment (MCI) and dementia. At death, a neuropathologic examination was done to quantify common pathologies linked to dementia. Results: Risk aversion at study onset ranged from 0.05–0.91 (mean: 0.32, standard deviation: 0.31). During a mean of 4.6 years of follow-up, 123 (of 874) developed dementia. Higher risk aversion was associated with higher dementia incidence (hazard ratio [HR]: 2.08; 95% confidence interval: 1.18, 3.65) and more rapid decline in episodic (estimate: –0.062; standard error [SE]: 0.019; t [3677]: –3.33; p < 0.001) and semantic (estimate: –0.039; SE: 0.015; t [3655]: –2.61; p = 0.009) memory but not in other cognitive systems. Of 702 people without cognitive impairment at baseline, 223 developed incident MCI. Higher risk aversion was associated with higher incidence of MCI (HR: 2.10; 95% confidence interval: 1.34, 3.29) and more rapid episodic memory decline. In 181 neuropathologically examined individuals, higher risk aversion was associated with higher levels of plaques, tangles, and cerebral amyloid angiopathy. Conclusion: The results support the hypothesis that high risk aversion in old age is partly an early sign of the pathology of Alzheimer disease.     

Serum lipoprotein levels, statin use, and cognitive function in older women

BACKGROUND: Few strategies are available for the prevention of cognitive impairment in elderly persons. Serum lipoprotein levels may be important predictors of cognitive function, and drugs that lower cholesterol may be effective for the prevention of cognitive impairment. OBJECTIVE: To determine whether serum lipoprotein levels, the 4-year change in serum lipoprotein levels, and the use of statin drugs are associated with cognition in older women without dementia. DESIGN, SETTING, AND PARTICIPANTS: An observational study of 1037 postmenopausal women with coronary heart disease enrolled in the Heart and Estrogen/progestin Replacement Study (participants at 10 of 20 centers). MAIN OUTCOME MEASURE: The Modified Mini-Mental State Examination was administered at the end of the study after 4 years of follow-up. Women whose score was less than 84 points (>1.5 SDs below the mean) were classified as having cognitive impairment. Lipoprotein levels (total, high-density lipoprotein, and low-density lipoprotein [LDL] cholesterol and triglycerides) were measured at baseline and at the end of the study; statin use was documented at each visit. RESULTS: Compared with women in the lower quartiles, women in the highest LDL cholesterol quartile at cognitive testing had worse mean plus minus SD Modified Mini-Mental State Examination scores (93.7 plus minus 6.0 vs 91.9 plus minus 7.6; P =.002) and an increased likelihood of cognitive impairment (adjusted odds ratio, 1.76; 95% confidence interval, 1.04-2.97). A reduction in the LDL cholesterol level during the 4 years tended to be associated with a lower odds of impairment (adjusted odds ratio, 0.61; 95% confidence interval, 0.36-1.03) compared with women whose levels increased. Higher total and LDL cholesterol levels, corrected for lipoprotein(a) levels, were also associated with a worse Modified Mini-Mental State Examination score and a higher likelihood of impairment, whereas high-density lipoprotein cholesterol and triglyceride levels were not associated with cognition. Compared with nonusers, statin users had higher mean plus minus SD Modified Mini-Mental State Examination scores (92.7 plus minus 7.1 vs 93.7 plus minus 6.1; P =.02) and a trend for a lower likelihood of cognitive impairment (odds ratio, 0.67; 95% confidence interval, 0.42-1.05), findings that seemed to be independent of lipid levels. CONCLUSIONS: High LDL and total cholesterol levels are associated with cognitive impairment, and lowering these lipoprotein levels may be a strategy for preventing impairment. The association between statin use and better cognitive function in women without dementia requires further study.     

Memory impairment on free and cued selective reminding predicts dementia

OBJECTIVE: To estimate the relative rates of dementia in initially nondemented subjects with and without memory impairment defined by baseline free recall from the Free and Cued Selective Reminding (FCSR) test. BACKGROUND: Our approach to identifying persons at high risk for future dementia is to show the presence of memory impairment not caused by other cognitive deficits by using a memory test that controls attention and cognitive processing. When the conditions of testing are not adequately controlled, prediction is reduced because age-associated memory deficits due to other cognitive deficits are confused with dementia-associated memory deficits. METHODS: Longitudinal evaluation of 264 initially nondemented, elderly community volunteers from the Einstein Aging Study with clinical and psychometric examinations every 12 to 18 months for up to 10 years. MAIN OUTCOME MEASURES: Dementia was defined by an algorithmic definition that required a Blessed Information Memory and Concentration score >8 and clinical evidence of functional decline. RESULTS: Thirty-two incident cases of dementia developed during follow-up. Survival analyses indicated that subjects with impaired free recall at baseline had dementia develop (relative risk = 75.2, 95% CI = 9.9 to 567) over 5 years of follow-up at dramatically higher rates than subjects with intact free recall after adjusting for age, gender, and education. CONCLUSION: Poor performance on free recall from FCSR predicts future dementia. These findings support the existence of a preclinical phase of dementia characterized by memory impairment, which is present for at least 5 years before diagnosis.     

Stability and functional correlates of memory-based classification in older schizophrenia patients.

OBJECTIVE: There is an increasing interest in the usefulness of neurocognitive subtyping of schizophrenia. The classification of schizophrenia patients with cortical versus subcortical impairments has recently been validated with both neuropsychological and neurobiological measures. The authors examined the stability and correlations of these classifications with longitudinal assessments in older, chronically ill schizophrenia patients. METHODS: Older, chronically ill patients (N=589) were classified on the basis of their baseline profile, and a subset (N=243) was followed for periods up to 8 years, with data analyses conducted to evaluate the stability of these profiles, to determine whether classification into cortical or subcortical impairment at baseline predicts changes in self-care and social functioning at endpoint, up to 8 years later. RESULTS: Cortical profiles were most common and most stable over time, with the majority of patients with a subcortical profile at baseline found to have a cortical profile at follow-up. Those patients whose subcortical impairment profile was stable over time had less severe cognitive and functional impairments at baseline than those whose profile was found to be cortical at follow-up. DISCUSSION: Cortical profiles of memory impairment were associated with substantial cognitive impairments at baseline and did not predict risk for subsequent cognitive decline, whereas subcortical profiles were associated with worsening of cognitive impairments in about half of the cases. Those patients with more severe negative symptoms and cognitive and functional impairments within the subcortical group were most likely to decline.     

Metabolic syndrome and cognitive decline

Over 33% of women and 20% of men aged 65 and older will develop dementia during their lifetime, and many more will develop a milder form of cognitive impairment. Given the anticipated exponential increase in both the incidence and prevalence of cognitive impairment in the next century, it is critical to identify preventative strategies to thwart this critical public health issue. The metabolic syndrome is comprised of five cardiovascular risk factors that include abdominal obesity, hypertriglyceridemia, low high density lipoprotein (HDL) levels, hypertension, and hyperglycemia. The prevalence of the metabolic syndrome, similar to that for cognitive disorders, increases dramatically with age. While several of the individual components of the metabolic syndrome have been linked to risk of developing dementia and cognitive impairment, few studies have looked at the components of the metabolic syndrome as a whole. We found, in two separate studies involving elders of different ethnicities, that the metabolic syndrome is a risk factor for accelerated cognitive aging. This was especially true for elders with the metabolic syndrome and with elevated serum level of inflammation. Several possible mechanisms may explain the association between the metabolic syndrome and cognitive decline including micro- and macro-vascular disease, inflammation, adiposity and insulin resistance. If metabolic syndrome is associated with increased risk of developing cognitive impairment, regardless of mechanism, then early identification and treatment of these individuals might offer avenues for disease course modification.     

Does antipsychotic polypharmacy increase the risk for metabolic syndrome?

OBJECTIVE: To determine whether the coprescribing of two or more antipsychotics, a relatively frequent practice with little data to support its safety and efficacy, is associated with an increased prevalence of metabolic syndrome. METHODS: 364 newly admitted adults treated with second-generation antipsychotics underwent assessments evaluating antipsychotic polytherapy, and of the presence of metabolic syndrome and triglycerides/high-density lipoprotein cholesterol ratio>3.5 (TG/HDL), a sensitive marker of insulin resistance. The correlates of antipsychotic polytherapy and associations with metabolic syndrome and TG/HDL were determined by univariate comparisons and multiple logistic regression analyses. RESULTS: Antipsychotic polytherapy was present in 70 patients (19.2%) and was significantly more likely in patients with schizophrenia and those treated with clozapine, quetiapine or ziprasidone (p<0.0001). Compared with antipsychotic monotherapy, polytherapy was associated with elevated rates of metabolic syndrome (50.0% vs. 34.3%, p=0.015) and TG/HDL (50.7% vs. 35.0%, p=0.016). However, in logistic regression analyses, metabolic syndrome was significantly associated with higher body mass index (BMI), older age, a diagnosis of bipolar disorder or schizophrenia, and cotreatment with a first-generation antipsychotic (r(2): 0.25, p<0.0001). The TG/HDL marker of insulin resistance was associated with higher BMI, male sex, Caucasian race and absence of aripiprazole treatment (r(2): 0.14, p<0.0001). Antipsychotic polypharmacy dropped out of both multivariate models. CONCLUSIONS: Compared with patients receiving antipsychotic monotherapy, patients on antipsychotic polytherapy have higher rates of metabolic syndrome and lipid markers of insulin resistance. However, antipsychotic polytherapy is not independently associated with the prevalence of these abnormalities, which are related to known demographic, clinical and anthropometric risk factors.     

Predictive validity and diagnostic stability of mild cognitive impairment subtypes

BackgroundMild cognitive impairment (MCI) is subclassified into four subtypes by the presence of impairment in the memory domain (amnestic vs nonamnestic) and the number of impaired cognitive domains (single vs multiple). However, predictive validity for outcomes of these criteria and the diagnostic stability of the subtypes are questionable.MethodsWe investigated the outcomes of 140 patients with MCI who participated in the baseline study of the Korean Longitudinal Study on Health and Aging and completed the 18-month follow-up evaluation (mean duration of follow-up = 1.57 ± 0.24 years). We evaluated the predictive validity of the criteria using multinomial logistic regression analyses, and the diagnostic stability of MCI subtypes using annual conversion rates between subtypes.ResultsCompared with the single-domain type (MCIs), the multiple-domain type (MCIm) had a lower chance of reversion to normal cognition (MCIm = 10.94%, MCIs = 43.42%) and higher risk of conversion to dementia (MCIm = 23.44%, MCIs = 5.26%). The difference in the reversion rate between the multiple- and single-domain type was statistically significant (odds ratio = 0.233, 95% confidence interval = 0.070–0.771, P = .017). However, neither the chance of reversion nor the risk of conversion was different between amnestic and nonamnestic subtypes. Among the 81 participants who neither converted to dementia nor reverted to normal cognition, 39 converted to different subtype (annual conversion rate = 17.74%).ConclusionsThe number of impaired cognitive domains, but not the presence of memory impairment, predicted poor outcomes in people with MCI. However, MCI subtype was diagnostically unstable.     

Snoring and the metabolic syndrome in women

OBJECTIVE: The main objective was to examine the association between metabolic syndrome, snoring and sleep quality among women. METHODS: The study sample comprised healthy women (30-65 years) from the greater Stockholm area. Snoring and sleep quality were measured by the Karolinska Sleep Questionnaire. The metabolic syndrome was defined as the presence of two or more of the following components: (1) fasting serum glucose level > or =7.0 mmol/L; (2) arterial blood pressure > or =140/90 mmHg; (3) fasting serum triglycerides > or =1.7 mmol/L and/or HDL cholesterol <1.05 mmol/L; and (4) obesity (waist-to-hip ratio >0.85 and/or BMI > or =28 kg/m2). RESULTS: After adjustment for age, the risk ratio of metabolic syndrome among snorers as compared to non-snorers was 4.50 (95% CI: 1.71-11.86; p=0.002). This association persisted after controlling for menopausal status, educational level, smoking, fatigue and exercise habits. Poor sleep quality showed a trend (OR: 3.31; 95% CI: 0.89-12.21; p=0.073) towards an increased risk for metabolic syndrome, but this did not reach statistical significance. CONCLUSIONS: Snoring may be a strong predictor for metabolic syndrome in middle-aged women. These findings show that snoring women are not only at increased risk for individual risk factors associated with cardiovascular disease and type 2 diabetes, but also for metabolic syndrome.     

Smoking, drinking, and incident cognitive impairment: a cohort community based study included in the Gospel Oak project

OBJECTIVES: Recent longitudinal studies have reported that smoking increases risk for cognitive impairment and that moderate alcohol intake could be preventive.The association between both cigarette smoking and alcohol drinking and incident cognitive impairment was studied in a representative population. METHODS: This is a 1 year prospective population based cohort study of all residents aged 65 or over in the electoral ward of Gospel Oak in London, UK (n=889). Cognitive impairment was assessed at baseline and 1 year later using the organic brain syndrome (OBS) cognitive impairment scale from the short CARE structured assessment. Subjects who were cognitively impaired at baseline were excluded from this analysis. RESULTS: The prevalence of OBS cognitive impairment was 10.4% at index assessment and the 1 year cumulative incidence of cognitive impairment was 5.7%. Cognitive impairment was not associated with use of alcohol, although there was a non-significant association in the direction of a protective effect against onset of cognitive impairment for moderate drinkers compared with non-drinkers and heavy drinkers. Current smoking status predicted cognitive impairment (risk ratio (RR) 3.7; (95% confidence interval (95% CI)=1.1-12.3) independently from sex, age, alcohol, occupational class, education, handicap, depression, and baseline cognitive function. CONCLUSIONS: Smoking seems to be a prospective risk factor for incident cognitive impairment; thus encouragement of older people to stop smoking could be considered as part of a strategy to reduce the incidence of cognitive impairment.     

Association of inflammatory markers with hearing impairment: The English Longitudinal Study of Ageing

BackgroundHearing impairment is common at an older age and has considerable social, health and economic implications. With an increase in the ageing population, there is a need to identify modifiable risk factors for hearing impairment. A shared aetiology with cardiovascular disease (CVD) has been advanced as CVD risk factors (e.g. obesity, type 2 diabetes) are associated with a greater risk of hearing impairment. Moreover, low-grade inflammation is implicated in the aetiology of CVD. Accordingly, our aim was to investigate the association between several markers of inflammation – C-reactive protein, fibrinogen and white blood cell count – and hearing impairment.MethodsParticipants of the English Longitudinal Study of Ageing aged 50–93 were included. Inflammatory marker data from both wave 4 (baseline, 2008/09) and wave 6 (2012/13) were averaged to measure systemic inflammation. Hearing acuity was measured with a simple handheld tone-producing device at follow-up (2014/15).ResultsAmong 4879 participants with a median age of 63 years at baseline, 1878 (38.4%) people presented hearing impairment at follow-up. All three biomarkers were positively and linearly associated with hearing impairment independent of age and sex. After further adjustment for covariates, including cardiovascular risk factors (smoking, physical activity, obesity, diabetes, hypertension, cholesterol), memory and depression, only the association with white blood cell count remained significant: odds ratio per log-unit increase; 95% confidence interval = 1.46; 1.11, 1.93.ConclusionsWhile white blood cell count was positively associated with hearing impairment in older adults, no relationships were found for two other markers of low-grade inflammation.     

Frequency of cognitive impairment dramatically increases during the first 5 years of multiple sclerosis

Previous studies have demonstrated that cognitive impairment is already present in patients suffering from a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). However, little is known about the course of cognitive impairment after the occurrence of a CIS. In order to characterise the early evolution of cognitive impairment, the authors assessed during a 5-year follow-up period a group of 24 CIS patients with high risk of developing MS. Longitudinal neuropsychological assessment was performed at two time points (baseline and year 5) in patients and controls (baseline and year 1). At year 5, 54% of patients showed cognitive impairment against 29% at baseline. Multiple regression models showed that patients with a higher T(2) lesion load at baseline had a higher cognitive impairment at year 5. This longitudinal study performed in CIS patients showed that the frequency of cognitive impairment increases dramatically during the first 5 years following a CIS and that the cognitive status at year 5 was predictable by conventional MRI parameters recorded at baseline.     

Differential evolution of cognitive impairment in nondemented older persons: results from the Kungsholmen Project

OBJECTIVE: This study was a prospective, population-based examination of the evolution of cognitive impairment, no dementia (CIND). METHOD: Subjects 75 years old or older living in Stockholm were assessed at baseline and 3 and 6 years later. The severity of CIND was based on age- and education-specific norms on the Mini-Mental State Examination and was classified as mild (N=212), moderate (N=96), or severe (N=57). Mortality, progression to dementia (DSM-III-R), cognitive stability, and cognitive improvement were studied as main outcomes. RESULTS: Of the individuals with mild CIND, 63 (34%) died, 65 (35%) progressed to dementia, 21 (11%) remained stable, and 46 (25%) improved between baseline and first follow-up. The relative risks of progressing to dementia by first follow-up in the subjects with mild, moderate, and severe CIND were 3.6, 5.4, and 7.0, respectively. The relative risk of death decreased with increasing severity of impairment. Individuals who improved at first follow-up did not have a significantly higher risk of later progressing to dementia than subjects who had never been impaired (relative risk=1.4). The absence of a subjective memory complaint predicted improvement (odds ratio=5.4). CONCLUSIONS: CIND is a heterogeneous condition: similar proportions of subjects progress to dementia, death, and cognitive improvement over 3 years. There is no increased future risk of progressing to dementia in CIND subjects who improve during that period.     

Probable Alzheimer's disease patients presenting as "focal temporal lobe dysfunction" show a slow rate of cognitive decline

Several authors have recently shown that anterograde amnesia is often associated with semantic memory impairment in amnesic MCI patients. Similarly, after the MCI condition, some patients who convert to Alzheimer's disease (AD) show the classic onset (cAD) characterized by the impairment of memory and executive functions, whereas other AD patients show isolated defects of episodic and semantic memory without deficits in other cognitive domains. The latter have been considered an AD variant characterized by 'focal Temporal Lobe Dysfunction' (TLD). The aim of the present study was to assess the differences in disease progression between cAD and TLD. For this purpose a continuous series of newly diagnosed probable AD patients presenting as cAD (n = 30) and TLD (n = 25), matched for severity, and 65 healthy controls underwent a comprehensive neuropsychological evaluation at baseline; TLD and cAD were re-evaluated at a 24-month follow-up. At follow-up, TLD patients showed no significant worsening of cognitive functions, whereas cAD subjects displayed a significant worsening in all explored cognitive domains. In conclusion, our results confirm that probable AD presenting as TLD represents a specific onset of AD characterized by a slower rate of progression.