S. Muratli

Importance of hypoglycemia on the risk of Alzheimer's disease in elderly subjects with diabetes mellitus.

Dear editor We read the article on the study of “Link between type 2 diabetes and Alzheimer’s disease: from epidemiology to mechanism and treatment” by Li et al.1 The review is very detailed and rational, considering the link between diabetes and Alzheimer’s disease and giving a new outlook as type 3 diabetes. It provides important information about the effects of the hyperglycemic complications of diabetes and treatment of dementia. We would like to emphasize a very important aspect of the diabetes–dementia association. The negative effects of acute hypoglycemia on executive function in adults with diabetes are well known.2 Recent data indicate that hypoglycemic events may also precipitate dementia in the chronic period.3–5 In a 27-year long longitudinal study involving 16,667 diabetic subjects with a mean age of 65 years, 11% developed dementia.3 Among subjects who developed dementia, 16.95% had at least one episode of hypoglycemia. Another prospective population-based study that involved 783 elderly adults suggested that subjects who experienced hypoglycemic events had a twofold increased risk of developing dementia compared with those who did not.4 Another study involving 169,114 cases with new-onset dementia indicated that subjects with diabetes had a higher risk of dementia if they had prior cerebrovascular disease, peripheral vascular disease, chronic kidney disease, or a history of one or more hospital admissions for hypoglycemia.5 Contribution of hypoglycemia to the development of dementia was also observed in a cohort study that consisted of 1,342 diabetic patients in Italy.6 In this study, multivariate analysis showed that advanced age, female sex, and hypoglycemic events were independently associated with increased risk of dementia. Moreover, the risk was higher in subjects under oral hypoglycemic drugs. There are also experimental studies regarding the effects of hypoglycemia on the risk of dementia. Hypoglycemia leads to hyperphosphorylation of tau in a study performed on rat brain cells.7 Patients with elderly-onset type 2 diabetes have better glycemic control and lower rates of microvascular complications than elderly subjects with adult-onset diabetes.8 Furthermore, hypoglycemic complications have the potential to be more dangerous because adrenergic symptoms of hypoglycemia are more silent in elderly diabetics.9 Thus, consideration of the adverse effects of hypoglycemia is crucial, especially in frail elderly subjects. Although it is important to control hyperglycemia in elderly subjects, avoidance from hypoglycemia is of paramount importance to lower the risk of dementia. In this context, individualized glycemic targets should be utilized.

Confounders Regarding the Association of Insulin Resistance and Alzheimer Disease.

Confounders Regarding the Association of Insulin Resistance and Alzheimer Disease To the Editor We read the article by Willette et al1 with interest. The findings of this study are important because insulin resistance is a growing health problem, and measures to decrease the incidence of Alzheimer disease (AD) are urgently needed. However, we have some comments on this welldesigned and well-performed study. First, checking fasting glucose levels only once may be insufficient to diagnose or exclude diabetes mellitus (DM). For an accurate diagnosis of DM, fasting glucose levels of 126 mg/dL or greater on 2 occasions (to convert to millimoles per liter, multiply by 0.0555), a glycated hemoglobin level of 6.5% or greater (to convert to proportion of total hemoglobin, multiply by 0.01), a random blood glucose level of 200 mg/dL or greater with accompanying symptoms, or a second-hour blood glucose level at 75-g oral glucose tolerance test of 200 mg/dL or greater are needed. Older adults with DM, especially, may have normal fasting blood glucose levels.2 To draw more accurate conclusions regarding the association of insulin resistance and AD, measuring postprandial glucose levels and/or glycated hemoglobin levels would prove beneficial. Second, reactive hypoglycemic episodes and glucose variability may also increase the risk for AD in those with insulin resistance. A prospective population-based study that involved 783 elderly adults suggested that patients who experienced hypoglycemic events had a 2-fold increased risk for developing dementia compared with those who did not.3 Kim et al4 observed that a greater degree of visit-to-visit glucose variability resulted in deterioration of certain cognitive functions in patients with DM. Notably, this association was independent from mean glucose levels. Thus, in the study by Willette et al,1 glucose variability might have affected brain glucose metabolism negatively in individuals with insulin resistance. Matthews et al5 investigated the association between adherence to a Mediterranean diet and physical activity and brain glucose metabolism and amyloid burden. They showed that physical activity and adherence to a Mediterranean diet were associated with better brain-glucose metabolism and decreased brain-amyloid burden. Interestingly, important confounders, such as apolipoprotein E genotype, hypertension, and insulin resistance, did not attenuate these associations. Thus, physical activity level and diet characteristics may also be important confounders. In conclusion, we suggest that consideration of the factors mentioned here (reactive hypoglycemia, glucose variability, physical activity level, and diet characteristics) would make interpretation of the findings of Willette et al1 more accurate. Future studies regarding the association of insulin resistance and AD would better assess these factors as well.

Body mass index and functional status in community dwelling older Turkish males

Abstract Disability is utmost important on an aging populations health. Obesity is associated with increased risk for disability. On-the-other-hand, higher-BMI is reported as associated with better functionality in older people in some reports defined as “obesity paradox”. There is some evidence on differential relationship between body weight status and functionality by living setting gender, and different populations. We studied the relation between body mass index and functionality in Turkish community dwelling older males accounting for the most confounding factors: age, multimorbidity, polypharmacy and nutritional status. This is a cross-sectional study in a geriatric outpatient clinic of a university hospital. Functionality was assessed with evaluation of activities of daily living (ADL) and instrumental activities of daily living (IADL) scales. Nutrition was assessed by mini-nutritional assessment test. Two hundred seventy-four subjects comprised our study cohort. Mean age was 74.4 ± 7.1 years, BMI was 25.8 ± 4.4 kg/m2. Linear regression analysis revealed significant and independent association of lower BMI with higher ADL and IADL scores (B = 0.047 and B = 0.128, respectively) (p < 0.05) and better nutritional status (B = 1.94 and B = 3.05, respectively) (p < 0.001) but not with the total number of medications. Higher IADL score was associated with younger age and lower total number of diseases (B = 0.121, B = 0.595, respectively) (p < 0.05) while ADL was not. We suggest that lower BMI is associated with better functional status in Turkish community-dwelling male older people. Our study recommends longitudinal studies with higher participants from different populations, genders and living settings are needed to comment more.

Potential contribution of diabetes mellitus to orthostatic blood pressure fall and conversion of mild cognitive impairment to dementia.

Dear editor We read the article “Orthostatic blood pressure in people with mild cognitive impairment predicts conversion to dementia” by Hayakawa et al1 with interest. It is well-known that many individuals with mild cognitive impairment (MCI) progress to dementia.2 However, we do not exactly know which risk factors increase this risk and to what extent. Hypertension is a risk factor for Alzheimer’s disease and vascular dementia. However, the findings of this study make us consider hypotension as a new risk factor for dementia. Furthermore, a recently published 6-year prospective general population cohort study suggested that not only orthostatic hypotension (OH), but also symptoms of OH seemed to be risk factors for cognitive decline.3 Notably, in the study by Elmstahl et al3, hypertension and diabetes mellitus (DM) were more common in subjects with dementia. We would like to make some comments on this well-designed study. The prevalence of DM is rather high in elderly individuals, and diabetic autonomic neuropathy may cause significant autonomic dysfunction. Furthermore, reactive hypoglycemic attacks and glucose variability may also increase the risk of Alzheimer’s disease in subjects with DM.4–6 Glucose variability and hypoglycemic attacks precipitated by insulin resistance may also affect conversion of MCI to dementia.7 Accurate diagnosis of DM is especially important in older adults who may not experience typical symptoms of hyperglycemia and may even have normal fasting blood glucose levels. Thus, the diagnosis of DM may be easily overlooked in elderly subjects.8 However, in the study by Hayakawa et al1, a detailed assessment for the presence or absence of DM is not reported and the rate of DM in the study population seems to be lower than anticipated. We suggest that for an accurate diagnosis of DM, checking fasting glucose, postprandial glucose, and HbA1c levels is essential.8 In conclusion, undiagnosed DM, glucose variability, and postprandial hypoglycemia might have contributed significantly to OH and to conversion of MCI to dementia in this study.

Higher vitamin D levels may be associated with higher levels of sunlight exposure and higher intake of vitamin D by diet

Dear editor We read the article by Al-Eisa et al1 entitled “Correlation between vitamin D levels and muscle fatigue risk factors based on physical activity in healthy older adults,” regarding an important subject – the association among vitamin D deficiency, physical activity, and muscle fatigue; the findings of this study indicate that increased physical activity is associated with higher vitamin D levels and less fatigue. We would like to comment on this well-designed and performed study. In this study, significantly higher levels of vitamin D concentrations were reported in physically active participants compared with those with lower physical activity. However, there were no data on sunlight exposure or the seasons in which the study was conducted. Physically active participants may have higher exposure to sunlight compared with those with lower physical activity. Furthermore, subjects with higher physical activity may have a healthier diet behavior, which means they may have higher vitamin D intake by diet. If these data are not available, it is better to mention this as a limitation of the study. Second, the authors stated that they evaluated fatigue using the visual analog scale (VAS) as well. However, the “Methods” section indicates that VAS was used to assess pain. The authors should clearly mention if VAS was used to assess pain, fatigue, or both. Finally, the mean total and free calcium levels seem to be erroneously reported. In particular, physically active subjects seem to have severe hypercalcemia when their total and free calcium levels in Table 2 are taken into account.

P322: Simplified Nutritional Appetite Questionnaire (SNAQ): an alternative test for geriatric nutritional assessment

Introduction: Nutrition is affected negatively in the old age due to physiological changes, acute-chronic diseases, oral-dental health problems, polypharmacy, economical factors, difficulties in food supply, difficulties in preparing and eating food. In this study we aim to evaluate nutritional status of community-dwelling older people by using Simplified Nutritional Appetite Questionnaire (SNAQ) and Mini Nutritional Assessment – Short Form (MNA-SF). Methods: Patients over 75 years of age admitted to outpatient clinic between 3 January 2013 and 31 December 2013 were enrolled. According to comprehensive geriatric assessment; height-weight measurements, weight loss, special diets and difficulty swallowing asked. The participants were evaluated with Katz Activities of Daily Living (ADL) and Lawton-Brody Instrumental Activities of Daily Living scores (IADL), Simplified Nutritional Appetite Questionnaire, Mini Nutritional Assessment Short-Form. Results: A total of 203 elders were included in the study. 33% were male and 67% were female. Mean age was 80.9 years. As a result of MNA-SF scores 5.4% had malnutrition and 22.7% had malnutrition risk. In our study group mean SNAQ score 15.5±2.4. Due to SNAQ scores total 20.7% (women 25.7%, men 10.4%) were at risk of weight loss (Table 1). We observed that a positive advanced correlation between SNAQ and functionality by ADL, IADL, the hand grip, physical activity and ambulation status (Table 2). Conclusions: Nutrition and appetite status of the elderly is an important part of a comprehensive geriatric assessment. It should be performed routinely. SNAQ form can be preferred as a alternative and a quick method for screening nutrition.