Dietary patterns and cognition in older persons.

PURPOSE OF REVIEW: The current article reviews recently published evidence of the important role that specific dietary patterns may hold on preventing cognitive impairment and dementia over aging. RECENT FINDINGS: Specific dietary patterns attributed to targeting cardiovascular risk factors may protect against the development of mild cognitive impairment (MCI) and dementia, especially Alzheimer's disease. Numerous epidemiological studies have strongly suggested that multinutrient approaches using the Mediterranean diet (Med diet), dietary approach to systolic hypertension (DASH) and the Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) are associated with a lower risk of cognitive impairment, MCI and Alzheimer's disease in older persons. This multinutrient approach seems to hold better outcomes than single nutrient intervention. There is only one randomized clinical trial (PREDIMED study) showing an improvement in cognitive performance over time in those undergoing a Med diet protocol. SUMMARY: Nutrition is an essential and modifiable risk factor that plays a role on preventing and/or delaying the onset of dementia. There is sufficient evidence to hypothesize testing neuroprotective dietary patterns on cognition in randomized clinical trials in older persons. Healthy dietary patterns such as the Med diet, DASH and MIND deserve further attention in randomized clinical trials on cognitive performance outcomes.

IAGG/IAGG GARN International Survey of End-of-Life Care in Nursing Homes.

This article reports the findings of a survey on end-of-life (EOL) care in nursing homes of 18 long-term care experts across 15 countries. The experts were chosen as a convenience-based sample of known experts in each country. The survey was administered in 2016 and included both open-ended responses for defining hospice care, palliative care, and "end of life," and a series of questions related to the following areas-attitudes toward EOL care, current practice and EOL interventions, structure of care, and routine barriers. Overall experts strongly agreed that hospice and palliative care should be available in long-term care facilities and that both are defined by holistic, interdisciplinary approaches using measures of comfort across domains. However, it appears the experts felt that in most countries the reality fell short of what they believed would be ideal care. As a result, experts call for increased training, communication, and access to specialized EOL services within the nursing home.

Inappropriate prescription of low molecular weight heparins for thromboprophylaxis among older hospitalized patients.

AIM: To investigate the prevalence and clinical correlates of overprescribing and underprescribing of low molecular weight heparins (LMWHs) for thromboprophylaxis among older medical inpatients. METHODS: Eight hundred seventy six patients (mean age 81.5 ± 7.6 years, female gender 57.2 %) enrolled in a multicenter observational study of seven acute care wards of geriatric medicine in Italy. The risk of venous thromboembolism was ascertained by calculating the Padua score for each patient. Patients receiving appropriate prescription of LMHW during stay were compared to those receiving LMHW with a Padua score <4 (overprescribing group). Similarly, patients with a high thromboembolic risk (Padua score ≥4) but not receiving LMHW (underprescribing group) were compared to patients appropriately not receiving LMHW during stay. Independent correlates of overprescribing and underprescribing were investigated by logistic regression analysis. RESULTS: Overall, 42.8 % of patients had a Padua score ≥4. LMWHs were overprescribed in 7.3 % and underprescribed in 25.2 % of patients. The number of lost basic activities of daily living (BADL) (OR = 0.25; 95 % CI 0.15-0.41) and the number of diagnoses (OR = 0.76; 95 % CI 0.61-0.95) were inversely associated with LMWH overprescription. Conversely, older age (75-84 years: OR = 2.39; 95 % CI 1.10-5.19-85 years or more: OR = 3.25, 95 % CI 1.40-7.61), anemia (OR = 1.80, 95 % CI 1.05-3.16), pressure sores (OR = 4.15, 95 % CI 1.20-14.3), number of lost BADL at the admission (OR = 3.92, 95 % CI 2.86-5.37) and number of diagnoses (OR = 1.29, 95 % CI 1.15-1.44) qualified as significant correlates of LMWH underprescription. DISCUSSION: Underprescription and, to a lesser extent, overprescription still represent an issue among older medical inpatients. CONCLUSION: Implementing risk-stratifying scores into clinical practice may improve appropriateness of LMWHs prescribing during hospitalization.

Tighter glycemic control is associated with ADL physical dependency losses in older patients using sulfonylureas or mitiglinides: Results from the DIMORA study.

BACKGROUND: There is growing evidence that tight glycemic control may be more harmful than beneficial in older persons with Type 2 diabetes (T2DM). It remains controversial if tight glycemic control (lower glycated hemoglobin A1c (A1c)) is associated with functional impairments in older frail patients with T2DM. We explored associations between A1c and losses in Activities of Daily Living (ADLs) in diabetic nursing home (NH) patients and tested for differences according to anti-diabetic treatment: diet, anti-diabetic oral drug (AOD), insulin, combined insulin+AOD. METHODS: We conducted a cross-sectional study on 1845 older NH patients with T2DM from 150 sites across Italy. Complete evaluations on ADLs, glycemic control, anti-diabetic treatments, comorbidities, and clinical data were recorded. ANOVA was applied to compare clinical characteristics across A1c tertiles. Multivariate regression models evaluated associations between A1c and ADL losses. RESULTS: Patients had a mean age [SD]=82 [8] years; BMI=25.5 kg/m(2) [4.7]; Fasting Plasma Glucose (FPG)=7.4 [3.0] mmol/l; Post-prandial glucose (PPG)=10.3 [3.6] mmol/l; A1c=7.0% (54 mmol/mol), ADL losses=3.7 [1.8]. Compared to higher A1c tertiles, patients in the lower tertile had greater ADL losses, were more likely to use AODs, while less likely to use insulin or insulin+AOD. After adjusting for multiple confounders, impairments in ADLs were associated with tighter A1c levels (B=-0.014; p=0.002). Regression models according to anti-diabetic treatment showed that tighter A1c levels continued as independent determinants of ADL losses in patients using AODs (B=-0.023; p=0.001), particularly in those using sulfonylureas (B=-0.043; p<0.001) or mitiglinides (B=-0.044; p=0.050). CONCLUSIONS: Tighter glycemic control was associated with ADL physical dependency losses, especially in those using sulfonylureas and mitiglinides.

Disentangling the Impact of Chronic Kidney Disease, Anemia, and Mobility Limitation on Mortality in Older Patients Discharged From Hospital.

BACKGROUNDS: Chronic kidney disease (CKD), anemia, and mobility limitation are important predictors of mortality. We aimed at investigating the interactions between estimated glomerular filtration rate (eGFR), anemia, and physical performance on 1-year mortality in older patients discharged from acute care hospitals. METHODS: Four hundred and eighty seven patients enrolled in a multicenter, prospective observational study were included in the analysis. eGFR was estimated by the Berlin Initiative Study 1 equation. Anemia was defined on the basis of hemoglobin values. Mobility limitation was rated by the Short Physical Performance Battery (SPPB). Covariates included demographics, nutritional status, cognitive performance, and comorbidity. The outcome of the study was mortality over 1-year follow-up. Interactions among study variables were investigated by survival tree analysis. RESULTS: eGFR < 30 mL/min/1.73 m(2), anemia, and SPPB = 0-4 were significantly associated with mortality, as were hypoalbuminemia and cognitive impairment. Survival tree analysis showed that compared to patients with SPPB ≥ 4 and eGFR ≥ 46.7 mL/min/1.73 m(2) (ie, patients with the least mortality), patients with SPPB < 4 and hemoglobin < 12.2 g/dL had the highest risk of mortality [hazard ratio (HR) = 28.9, 95%CI 10.3-81.2]. Patients with SPPB ≥ 4 and eGFR < 46.7 mL/min/1.73 m(2) and those with SPPB > 4, hemoglobin ≥ 12.2g/dL, and eGFR ≥ 58.6 mL/min/1.73 m(2) had intermediate risk (HR = 6.58, 95%CI = 2.15-20.2, and HR = 15.11, 95%CI=4.42-51.7, respectively). Having SPPB < 4, hemoglobin ≥ 12.2 g/dL, and eGFR<58.6 mL/min/l.73 m(2) was not significantly associated with increased mortality (HR = 2.95, 95%CI = 0.74-11.8). CONCLUSIONS: Interactions among eGFR, anemia, and mobility limitation define different profiles of risk in older patients discharged from acute care hospitals, which deserve to be considered to identify patients needing special care and careful follow-up after discharge.

Advanced technology care innovation for older people in Italy: necessity and opportunity to promote health and wellbeing.

Even though there is a constant and accelerating growth of the aging population worldwide, such a rapid rise is negatively impacting available home and community services not able to encompass the necessities associated with the increased number of older people. In particular, there are increasing demands on e-health care services and smart technologies needed for frail elders with chronic diseases and also for those experiencing active aging. Advanced Technology Care Innovation for older persons encompasses all sectors (assistive technology, robotics, home automation, and home care- and institution-based healthcare monitoring, telemedicine) dedicated to promoting health and wellbeing in all types of living environments. Considering that there is a large concern and demand by older persons to remain in familiar social living surroundings, study projects joined with industries have been currently initiated, especially across Europe to improve health and wellbeing. This article will highlight the latest updates in Europe and, in particular in Italy, regarding scientific projects dedicated to unraveling how diverse needs can be translated into an up-to-date technology innovation for the growing elder population. We will provide information regarding advanced technology designed for those with specific geriatric-correlated conditions in familiar living settings and for individuals aging actively. This is an important action because numerous emerging developments are based on user needs identified by geriatricians, thus, underlining the indispensable role of geriatric medicine toward future guidelines on specific technology.

High prevalence of poor quality drug prescribing in older individuals: a nationwide report from the Italian Medicines Agency (AIFA).

BACKGROUND: Poor quality of drug prescribing in older persons is often associated with increased drug-related adverse events, hospitalization, and mortality. The present study describes a set of prescribing quality indicators developed by the Geriatrics Working Group of the Italian Medicines Agency (AIFA) and estimates their prevalence in the entire elderly (≥ 65 years) population in Italy. METHODS: We performed a cross-sectional study using 2011 data from the OsMed (Osservatorio dei Medicinali) database, which comprises all prescribed drugs that are reimbursed by the Italian National Healthcare System. Yearly prevalence of drug prescribing quality indicators in the Italian older population (n = 12,301,537) was determined. RESULTS: Overall, 13 quality indicators addressing polypharmacy, adherence to treatment of chronic diseases, prescribing cascade, undertreatment, drug-drug interactions, and drugs to be avoided were identified. Polypharmacy was common, with more than 1.3 million individuals taking greater than or equal to 10 drugs (11.3% of the study population). The prevalence of low adherence and undertreatment was also elevated and increased with advancing age, with highest prevalence occurring in individuals aged 85 years and older. Prevalence was less than 3% for quality indicators assessing the prescribing cascade, drug-drug interactions, and drugs to be avoided. CONCLUSIONS: These results confirm the high frequency of suboptimal drug prescribing in older adults, using a database that covers the whole Italian population. In general, this descriptive study may help in prioritizing strategies aimed at improving the quality of prescribing in elderly population.

Change of accent as an atypical onset of non fluent primary progressive aphasia.

Language disorders can be the first symptom of many neurodegenerative diseases, including Alzheimer's disease (AD) and primary progressive aphasia (PPA). The main variants of PPA are: the non-fluent/agrammatic variant, the semantic variant and the logopenic variant.Several additional variants of PPA, however, have been described and are considered as atypical presentations. We describe the case of a woman presenting a progressive isolated language disturbance, characterized by an early dysprosodia, phonological and semantic paraphasias, agrammatism, impairment in repetition, writing of non-words and sentence comprehension. This clinical picture pointed to an atypical presentation of the non-fluent variety. The frequent symptom overlap between the different variants of PPA, most likely reflecting differences in the topography of the pathological changes, needs to be considered in the definition of diagnostic criteria.

Validation of the 3-lead tele-ECG versus the 12-lead tele-ECG and the conventional 12-lead ECG method in older people.

We compared the diagnostic accuracy of 3-lead tele-ECGs to both 12-lead tele-ECGs and a conventional 12-lead ECG device (the gold standard). The subjects were older people (n = 107) with a mean age of 66 years. The overall agreement between two cardiologists on interpreting the 3-lead tele-ECG recordings was 97% (kappa = 0.96, P < 0.001) and it was 91% for the 12-lead tele-ECGs (kappa = 0.90, P < 0.001). We also found excellent agreement on the interpretation of the 3-lead tele-ECGs compared to the gold standard: 98% (kappa = 0.96, P < 0.001) and for the 12-lead tele-ECG compared to the gold standard: 98% (kappa = 0.96, P < 0.001). Bland-Altman plots showed that the apparent differences between the techniques were not clinically relevant. The use of a 3-lead tele-ECG device may be useful for reducing the delay in treating specific heart disease conditions, e.g. in older people affected by chronic heart disease who need frequent ECG monitoring.

Frailty and safety: the example of diabetes.

Frailty is considered a syndrome of decreased reserve and resistance to stressors and is clinically expressed as muscle weakness, poor exercise tolerance, factors related to body composition, sarcopenia and disability. In addition, there is a close relationship between age-related metabolic changes and the occurrence of comorbidities that may in turn lead to frailty.Even though the downward spiral of frailty is activated more quickly in older persons with type 2 diabetes, it is reversible with appropriate interventions before reaching a high level of severity. The hazard for geriatric patients with type 2 diabetes is that frailty encompasses diverse complications already associated with or caused by diabetes. Frailty is also associated with cognitive impairment, reduced ability to perform activities of daily living and increased expression of inflammatory and coagulation markers that may contribute to the adverse microvascular effects of diabetes. Although glycaemic control remains the main targeting achievement in type 2 diabetes, especially in well-functioning older persons, this is not appropriate for those with frailty. Frail elderly people with type 2 diabetes are a specific group in need of treatment parameters for both initial and maintenance therapy with oral antidiabetic agents. Therefore, the prescription of an antidiabetic agent in such individuals must take into consideration not only the standard goal of lowering hyperglycaemic levels, but also improving the quality of life and life expectancy. The clinical management of this population is currently particularly demanding, requiring special considerations with good medical decision making. Clinical aspects complicating diabetes care in older people include cognitive decline, physical functional decline and frailty. Available oral antidiabetic drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin), α-glucosidase inhibitors, thiazolidinediones and inhibitors of glucagon-like peptide 1 (GLP-1) degrading enzyme dipeptidyl peptidase 4. In addition, we will discuss injection treatment with GLP-1 analogues. This review will underline the association between diabetes and some frailty components in old patients and how specific antidiabetic agents may play a specific role in improving outcomes.

Telomere/Telomerase system: a new target of statins pleiotropic effect?

Statins are well established drugs for primary and secondary prevention of coronary artery disease (CAD). Despite the well-known ability of statins to lower cholesterol, it is now clear that clinical benefits are also substantially higher than expected and several clinical trials, like JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial) have indicated that such clinical effects are independent of cholesterol reduction. These cholesterol-independent actions have been named "pleiotropic effects" and include: anti-oxidation and anti-inflammatory effects, modulation of immune activation, stabilization of atherosclerotic plaque, decreased platelet activation, inhibition of cardiac hypertrophy, reduction of cytokine-mediated vascular smooth muscle cell (VSMC) proliferation and improvement of endothelial function. Recently, additional pleiotropic effects of statins on "cellular senescence" have been seen in different cell types, including endothelial progenitor cells (EPC), endothelial cells (EC), VSMC and chondrocytes. At the molecular level, the effect of statins on cellular senescence could be mediated by their interaction with the telomere/telomerase system. Recent evidence suggests that the anti-aging effects of statins are linked to their ability to inhibit telomere shortening by reducing either directly and indirectly oxidative telomeric DNA damage, as well as by a telomere capping proteins dependent mechanism. In this review, we discuss the pleiotropic effects of statins, focusing on the telomere/telomerase system. We will also present our current findings regarding leukocyte telomere length in very old people with myocardial infarction on statin therapy.

Mediterranean diet and mobility decline in older persons.

We examined whether adherence to a Mediterranean-style diet has positive effects on mobility assessed over a 9-year follow-up in a representative sample of older adults. This research is part of the InCHIANTI Study, a prospective population-based study of older persons in Tuscany, Italy. The sample for this analysis included 935 women and men aged 65 years and older. Adherence to the Mediterranean diet was assessed at baseline by the standard 10-unit Mediterranean diet score (MDS). Lower extremity function was measured at baseline, and at the 3-, 6- and 9-year follow-up visits using the short physical performance battery (SPPB). At baseline, higher adherence to Mediterranean diet was associated with better lower body performance. Participants with higher adherence experienced less decline in SPPB score, which was of 0.9 points higher (p<.0001) at the 3-year-follow, 1.1 points higher (p=0.0004) at the 6-year follow-up and 0.9 points higher (p=0.04) at the 9-year follow-up compared to those with lower adherence. Among participants free of mobility disability at baseline, those with higher adherence had a lower risk (HR=0.71, 95% CI=0.51-0.98, p=0.04) of developing new mobility disability. High adherence to a Mediterranean-style diet is associated with a slower decline of mobility over time in community-dwelling older persons. If replicated, this observation is highly relevant in terms of public health.

Common geriatric conditions and disabilities in older persons with chronic obstructive pulmonary disease.

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is one of the most prevalent chronic diseases among older persons worldwide and the rapid increase in commonly associated COPD-disabilities requires urgent awareness among healthcare professionals. The presence of pulmonary and extrapulmonary comorbidities is highly prevalent among COPD patients and complicates treatment management, especially in advanced age. Some of the most common geriatric conditions in COPD patients lead to respiratory function decline, physical function impairment with limited physical performance, cognitive decline, and depression. Unfortunately, the activation of each component may lead to the progression of the other, which, if not corrected, will lead to critical clinical outcomes such as disability (as seen by the worsening of each condition) and death. RECENT FINDINGS: Studies in older persons with COPD have shown that disability is mainly due to the severity of comorbidities that have been shown to significantly impact treatment options and the prognosis for such individuals. In addition to spirometric functional parameters, exercise performance and efficacy of specific therapeutic interventions may be useful indicators for overall health status and outcomes. The scientific literature underlines the necessity to use additional parameters other than spirometry for COPD patient monitoring. SUMMARY: As disability is a growing phenomenon in COPD and substantially impacts patient perception of the disease, we will highlight the recent literature regarding the importance of common geriatric conditions leading to disability in older COPD patients. In particular, we will discuss the impact of the following conditions in older patients with COPD: respiratory function decline, physical function impairment, and mood disorders. Clinical use for measuring such parameters in COPD elderly will aid in identifying those at risk for severe clinical decline.

Practical management problems of chronic obstructive pulmonary disease in the elderly: acute exacerbations.

PURPOSE OF REVIEW: Acute exacerbations of chronic obstructive pulmonary disease (ECOPDs) have numerous causes and are associated with increased mortality and hospitalization, especially in older patients. The urgent need to identify and enable timely treatment of ECOPDs is a necessity for physicians worldwide. This review will highlight the causes and optimal combinations of available treatments for such events in older populations. RECENT FINDINGS: The exact definition of exacerbations is lacking; however, it is agreed that such events are considered episodes of worsening of symptoms, leading to morbidity and death. The aging process is a consistent determinant for ECOPD events and is associated with worsening of COPD stages. The incidence of ECOPD rises across the worsening stages of COPD. Studies have shown that the frequency of exacerbations increases with age and correlated clinical outcomes are poorer than in younger patients. The risk of mortality has also been shown to be significantly higher after a hospital admission following an acute exacerbation. At the moment, the need to rapidly and correctly treat acute exacerbations is crucially important in the rapidly growing elderly population. SUMMARY: ECOPDs are extremely dangerous events for older patients with severe stages of COPD. There is an urgent need to identify risk factors, identify tolerable treatment guidelines and manage acute exacerbations in older patients with COPD.

Does concealed chronic kidney disease predict survival of older patients discharged from acute care hospitals?

We aimed at verifying whether unrecognized chronic kidney disease (CKD) (i.e., reduced estimated glomerular filtration rate in spite of normal serum creatinine) has prognostic significance in an unselected population of older patients discharged from 11 acute care hospitals located throughout Italy. Our series consisted of 396 participants aged 70 and older. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease (MDRD) study equation. We compared three groups: Normal renal function (normal serum creatinine levels and normal eGFR), concealed (normal serum creatinine levels and reduced eGFR), or overt (increased creatinine levels and reduced eGFR) renal failure. The relationship between renal function and 1-year mortality was evaluated using Kaplan-Meier curves and Cox regression analysis including potential confounders. Overall, 56 patients died over a cumulative follow-up time of 335 months, with an estimated incidence rate of 16.7/100 person-year (PY). The corresponding figures in patients with normal renal function, concealed CKD, and overt CKD were 9.8/100 PY (95% CI, 5.7-15.7), 28.3/100 PY (95% CI, 13.6-52.1), and 23.0 (95% CI, 15.4-33.0), respectively (log rank test p = 0.006). According to the fully adjusted model, both concealed (hazard ratio [HR], 2.35; 95% CI, 1.09-6.01) and overt CKD (HR, 2.09; 95% CI, 1.05-5.34) were significantly associated with the outcome. Concealed CKD contributes to profile the elderly patient at greater risk of death after being discharged from acute care medical wards. If confirmed in broader populations, this finding might have both clinical and epidemiological implications.

Impact of home patient telemonitoring on use of ß-blockers in congestive heart failure.

INTRODUCTION: Congestive heart failure (CHF), which typically affects older people, is characterized by high short- and mid-term mortality rates. However, despite accumulating evidence showing that administration of ß-blockers (ß-adrenoceptor antagonists) can improve the clinical status of CHF patients, use of these agents in adequate dosages in this setting is not routine. One reason for this appears to be a concern about a possible risk of bradyarrhythmia associated with use of ß-blockers. Telecardiology has recently been investigated as a means of constantly monitoring the heart rate of CHF patients in their homes. Its use may allay concerns about the risk of bradyarrhythmia and facilitate a more widespread use of ß-blockers in this context. OBJECTIVES: The primary objectives of this study were to assess the impact of telemonitoring on patients' adherence to prescribed therapeutic regimens, particularly ß-blockers, and to explore whether use of home telemonitoring reduces mortality and rate of re-admission to hospital in elderly CHF patients compared with normal specialized CHF team care. METHODS: A total of 57 patients with CHF (31 New York Heart Association [NYHA] class II, 23 NYHA class III and 3 NYHA class IV), with a mean ± SD age of 78.2 ± 7.3 years, were randomized to a control group who received standard care, based on routinely scheduled clinic visits, from a team specialized in CHF patient management, or to a home telemonitoring group (TM group), managed by the same specialized CHF team. Patients were followed up over 12 months. RESULTS: Compared with the control group, the TM group had a significant increase in the use of ß-blockers, HMG-CoA reductase inhibitors (statins) and aldosterone receptor antagonists. A reduction in nitrate administration compared with baseline was also seen in the TM group. The 12-month occurrence of the primary combined endpoint of mortality and hospital re-admission for CHF was significantly lower in the TM group than in the control group (p < 0.01). CONCLUSIONS: This study showed that a home-care model including telemonitoring of relevant clinical parameters may provide useful support in the management of patients with CHF. Home telemonitoring in CHF patients was associated with increased use of ß-blockers at appropriate doses, suggesting that this strategy reassured physicians regarding the safety of careful use of these agents in this setting. However, larger studies are required to confirm these findings. Our findings indicate that there is a need to investigate relevant parameters in CHF patients at the point of care (i.e. in patients' daily lives), which can in turn optimize ß-blocker and other drug therapy.

Moving against frailty: does physical activity matter?

Frailty is a common condition in older persons and has been described as a geriatric syndrome resulting from age-related cumulative declines across multiple physiologic systems, with impaired homeostatic reserve and a reduced capacity of the organism to resist stress. Therefore, frailty is considered as a state of high vulnerability for adverse health outcomes, such as disability, falls, hospitalization, institutionalization, and mortality. Regular physical activity has been shown to protect against diverse components of the frailty syndrome in men and women of all ages and frailty is not a contra-indication to physical activity, rather it may be one of the most important reasons to prescribe physical exercise. It has been recognized that physical activity can have an impact on different components of the frailty syndrome. This review will address the role of physical activity on the most relevant components of frailty syndrome, with specific reference to: (i) sarcopenia, as a condition which frequently overlaps with frailty; (ii) functional impairment, considering the role of physical inactivity as one of the strongest predictors of physical disability in elders; (iii) cognitive performance, including evidence on how exercise and physical activity decrease the risk of early cognitive decline and poor cognition in late life; and (iv) depression by reviewing the effect of exercise on improving mood and increasing positive well-being.

Rosiglitazone and cognitive stability in older individuals with type 2 diabetes and mild cognitive impairment.

OBJECTIVE: Studies have suggested that insulin resistance plays a role in cognitive impairment in individuals with type 2 diabetes. We aimed to determine whether an improvement in insulin resistance could explain cognitive performance variations over 36 weeks in older individuals with mild cognitive impairment (MCI) and type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 97 older individuals (mean +/- SD age 76 +/- 6 years) who had recently (<2 months) started an antidiabetes treatment of metformin (500 mg twice a day) (n = 30) or metformin (500 mg/day)+rosiglitazone (4 mg/day) (n = 32) or diet (n = 35) volunteered. The neuropsychological test battery consisted of the Mini-Mental State Examination (MMSE), Rey Verbal Auditory Learning Test (RAVLT) total recall, and Trail Making Tests (TMT-A and TMT-B) performed at baseline and every 12 weeks for 36 weeks along with clinical testing. RESULTS: At baseline, no significant differences were found between groups in clinical or neuropsychological parameters. Mean +/- SD values in the entire population were as follows: A1C 7.5 +/- 0.5%, fasting plasma glucose (FPG) 8.6 +/- 1.3 mmol/l, fasting plasma insulin (FPI) 148 +/- 74 pmol/l, MMSE 24.9 +/- 2.4, TMT-A 61.6 +/- 42.0, TMT-B 162.8 +/- 78.7, the difference between TMT-B and TMT-A [DIFFBA] 101.2 +/- 58.1, and RAVLT 24.3 +/- 2.1. At follow-up, ANOVA models tested changes in metabolic control parameters (FPI, FPG, and A1C). Such parameters improved in the metformin and metformin/rosiglitazone groups (P(trend) < 0.05 in both groups). ANCOVA repeated models showed that results for the metformin/rosiglitazone group remained stable for all neuropsychological tests, and results for the diet group remained stable for the MMSE and TMT-A and declined for the TMT-B (P(trend) = 0.024), executive efficiency (DIFFBA) (P(trend) = 0.026), and RAVLT memory test (P(trend) = 0.011). Results for the metformin group remained stable for the MMSE and TMTs but declined for the RAVLT (P(trend) = 0.011). With use of linear mixed-effects models, the interaction term, FPI x time, correlated with cognitive stability on the RAVLT in the metformin/rosiglitazone group (beta = -1.899; P = 0.009). CONCLUSIONS: Rosiglitazone may protect against cognitive decline in older individuals with type 2 diabetes and MCI.