the link between vascular risk factors and dementia has recently attracted considerable attention and the impact of diabetes on a significant correlation of such factors with dementia is consistent [ 14 ] . however , mild cognitive dysfunction remains undetected and untreated in a considerable proportion of patients , resulting in several difficulties when treating diabetic elderly individuals . in screening for dementia - related disorders , handy cognitive tests such as the mini - mental state examination ( mmse ) and the hasegawa dementia scale - revised ( hds - r ) we have proposed screening indices for alzheimer 's disease ( ad ) using some weighted subscales of the mmse and hds - r , which are useful to discriminate early ad in diabetic elderly subjects [ 5 , 6 ] . however , even such brief neuropsychological tests impose burdens on practitioners in ambulatory care , because the number of patients with diabetes is increasing markedly in japan . a more simple and succinct prescreening procedure is thus needed to identify individuals with high risks for cognitive decline among diabetic elderly subjects . in the diagnostic workup for patients with dementia , it is typical to obtain information from an informant about cognitive deficits and problems in daily functioning . it has been postulated that the informant 's perception of cognitive deficits correlates with objective memory testing and can differentiate between groups with and without dementia . a more reliable predictor can be a discrepancy between the demented patient 's and an informant 's reports on cognitive status . however , to obtain information on cognitive deficits from caregivers is usually difficult in the routine care of patients with diabetes . to overcome this dilemma in screening for ad in diabetic elderly subjects , we aimed to develop a disease - specific model for predicting mild to moderate ad . the first goal of this study was to administer a questionnaire about those patients ' perceptions of memory problems and impaired daily functioning that are specifically evident in ad . second , we aimed to test the association of vascular risk factors , such as hypertension , dyslipidemia , and obesity , with ad . the final goal was to propose a predictive index for ad using a comprehensive assessment of these clinical variables and to verify its propriety in nondiabetic participants . a total of 286 diabetic patients and 155 nondiabetic individuals aged 65 or older were recruited from the outpatient 's clinic of the kobe university hospital , japan . the institutional review boards of kobe university hospital approved the research protocol , and written informed consent was obtained from each patient and his or her family members . the diabetic group had 25 subjects with mild to moderate ad and the nondiabetic group had 30 . ad was diagnosed as  probable ad  from a complete medical , neuropsychological , and neuroimaging evaluation by the multidisciplinary geriatric team at each site , based on the criteria from the national institute of neurological and communicative disorders and stroke , and the alzheimer 's disease and related disorders association . in this study , mild to moderate ad was defined as a score of greater than 14 on the mmse . patients were evaluated to rule out other causes of cognitive impairment including alcohol or drug abuse , major depression , delirium , systemic cancer , chronic infections , stroke , hypoxia , severe cardiopulmonary disorders , nutritional disorders , intracranial mass lesions , psychoses , brain trauma , or other neurological disorders including parkinson disease or huntington disease . the cognitively normal participants comprised 261 and 125 participants in the diabetic and nondiabetic groups , respectively . for the primary selection of cognitive normal group , geriatric physicians , who were familiar to consultation of the demented disorders , asked the patients and their caregivers about their complaints on cognitive decline and the daily life function . their cognitive functions were evaluated using the mmse and a computerized test battery for ad screening . they had no neurological or psychiatric disorders . after this consultation , each physician determined their cognitive status as normal . during the first visit , one of three trained research assistants in the geriatric division assessed participants using a self - reported questionnaire that measures perception of memory deficits and impairment of activities in daily living ( adls ) . the questionnaire contained three questions about each patient 's perception of memory problems , which were derived from the cambridge examination for mental disorders of the elderly ( camdex ) interview on memory complaints . ( 1 ) do you have any complaints concerning your memory ? ( 2 ) do other people find you forgetful ? ( 3 ) do you often use notes to avoid forgetting things ? basic adls referred to the ability to complete simple functions including walking and showering , whereas instrumental adls comprised more complex activities required for independent living , including grocery shopping , managing finances , meal preparation , travel outside a familiar locality , taking medication , and using public transportation [ 14 , 15 ] . we assigned  1  and  0  , to  yes  and  no  answers for each question , respectively . information on diabetes and other vascular risk factors for dementia was obtained from clinical charts . body mass index ( bmi ) , blood pressure , levels of hba1c , total cholesterol , triglycerides , and high density lipoprotein ( hdl)-cholesterol , duration of diabetes , therapeutic use of antihyperglycemic agents and/or insulin ( insulin dose and frequency of injection per day ) , and previous hypoglycemic episodes ( number of occasions in the previous year ) were investigated . the participants were also asked questions on the compliance with diet and exercise therapies ( in minutes per week ) by the physicians . logistic regression analysis and  
  test were used to compare the demographic , subjective cognitive complaints , and vascular risk factors between subjects with ad and cognitively normal individuals in both groups . any significant items were then entered into a multivariate logistic regression to develop a model for predicting ad , using stepwise selection with an inclusion criteria of p < 0.15 and exclusion criteria of p > 0.2 . using a developed model , a receiver operating characteristic ( roc ) curve was constructed to test the relationship between sensitivity and specificity using varying cutoff points of the model for predicting ad . the demographic and clinical features of diabetic and nondiabetic subjects are presented in table 1 . among the subjects with diabetes , having ad was characterized by being older , being female , having a lower educational level , and having lower diastolic blood pressure compared with cognitively normal controls . in contrast , hba1c levels , duration of diabetes , and lipid profiles were not significantly different between subjects with ad and cognitively normal individuals . although pharmacological treatment of diabetes and previous hypoglycemic episodes have been reported to increase the risk of dementia [ 1 , 17 ] , the incidence of hypoglycemic episodes and the frequency of use of oral antihyperglycemic agents and/or insulin ( insulin doses , frequency of injection ) did not show any difference between the ad and cognitively normal groups . in nondiabetic participants , being female and having a lower bmi and lower diastolic blood pressure were characteristics of patients with mild to moderate ad . the overall mean scores and ranges of the mmse were 20.6 ( 1428 ) and 20.8 ( 1427 ) for ad in the diabetic and nondiabetic elderly subjects , respectively . cognitive status was also evaluated by a computerized neuropsychological test battery for screening ad , of which a score of 14 suggests normal cognition and one of 12 is associated with ad , according to the original study data of the developer . the averaged scores of this cognitive test among the diabetic and nondiabetic elderly subjects were 9.0 and 9.9 for those with ad , and 14.3 and 14.4 for the cognitively normal subjects , respectively . among three distinct questions on subjective memory complaints ( table 2 ) , self - perception of memory dysfunction noticeable by himself / herself was not different between subjects with ad and normal controls in both diabetic and nondiabetic participants , while subjective complaint of memory deficits noticeable by others was significantly increased among the patients with ad . responses to the question about the use of notes to avoid forgetting things tended to decrease in those with ad . although basic adls such as walking and showering were similar between the subjects with ad and the cognitively normal controls , the self - reported achievement of instrumental adls ( grocery shopping , managing finances , meal preparation , travel outside familiar surroundings , correct use of medication , and public transportation ) was significantly impaired in patients with ad among those with diabetes ( table 3 ) . in the nondiabetic group , activities for shower , finance management , cooking , traveling , medication compliance , and use of public transport were impaired in ad . to develop a model for predicting ad using stepwise selection , clinical variables that were shown to be different at p < this showed that advanced age ( p < 0.001 ) , lower education ( p < 0.001 ) , lower diastolic blood pressure ( p = 0.029 ) , memory dysfunction noticeable by others ( p = 0.018 ) , and impaired activity in taking medication ( p = 0.001 ) were independently correlated with ad in diabetic elderly subjects . the predicted probabilities from the multivariate logistic regression analysis in screening for ad were as follows : log p/(1p ) = 0.253x 
 10.078x 
 23.740x 
 31.888x 
 4 + 1.883x 
 51.405x 
 60.453x 
 76.769 ; where x 
 1 = age ( years ) , x 
 2 = diastolic blood pressure ( mmhg ) , x 
 3 = medication ( yes , 1 ; no , 0 ) ,  x 
 4 = shopping ( yes , 1 ; no , 0 ) , x 
 5 = memory dysfunction noticeable by others ( yes , 1 ; no , 0 ) , x 
 6 = travel outside familiar surroundings ( yes , 1 ; no , 0 ) , and x 
 7 = education ( years ) . roc analysis revealed a satisfactory discrimination for predicting ad in diabetic elderly subjects with a sensitivity of 95.2% and a specificity of 90.6% , when the cutoff point of the model was set at 0.7888 ( figure 1(a ) ) . when predicted probabilities from the regression analysis in diabetic participants were applied for nondiabetic subjects , a prediction of ad was discriminated with 56.7% sensitivity and 89.6% specificity . similarly , multivariate logistic regression revealed independent associations of lower diastolic blood pressure ( p = 0.001 ) and medication compliance ( p = 0.017 ) with ad in the nondiabetic group . the predicted probabilities for screening of mild to moderate ad in nondiabetic participants were found to be : log p/(1p ) = 0.156x 
 11.608x 
 22.791x 
 30.919x 
 41.11x 
 5 + 12.6 ; where x 
 1 = diastolic blood pressure ( mmhg ) , x 
 2 = sex ( male , 1 ; female , 0 ) , x 
 3 = medication ( yes , 1 ; no , 0 ) ,  x 
 4 = finance ( yes , 1 ; no , 0 ) , and x 
 5 = travel outside familiar surroundings ( yes , 1 ; no , 0 ) . this study demonstrates a simple but effective strategy that can be used in screening for mild to moderate ad in diabetic elderly subjects . although the significance of an informant 's perception of a patient 's cognitive deficits has been emphasized previously for detecting dementia [ 8 , 9 ] , our results clearly indicate that comprehensive assessment of symptomatic deficits of memory and daily functioning , together with vascular risk factors for dementia , enables the discrimination of a subject developing mild to moderate ad with good sensitivity and specificity . the best prediction was obtained by the multivariate regression model that included older age , lower educational level , lower diastolic blood pressure , memory deficits noticeable by others , and impaired instrumental adls ( shopping , medication , and travel outside familiar surroundings ) , which was specific for diabetic elderly subjects . for nondiabetic participants , a distinct set of variables including female gender , lower diastolic blood pressure , and impairment in dealing with finances , medication , and travel predicted ad . our results for the first time provide a handy and succinct tool to serve as an index for predicting mild to moderate ad in elderly japanese subjects with type 2 diabetes mellitus . this study indicates that particular questions about subjective memory complaints are predictive for ad in diabetic participants . this finding is somewhat surprising , given the rather mixed results in the literature on the value of subjective memory complaints . subjective complaints of memory deficits are often observed among subjects in the early stage of ad , but decrease gradually as the disease progresses . many studies have reported that subjective memory complaints are more often associated with depressed mood rather than cognitive impairment [ 8 , 20 , 21 ] . however , recent community - based studies with longitudinal designs indicate that memory complaints are predictive of cognitive decline and incident dementia , particularly in nondemented individuals with cognitive impairment , although not all studies show this association among aged persons [ 2228 ] . self - reported poor memory is indeed a main component of the diagnostic criteria for mild cognitive impairment . in this connection , a clear definition of memory complaints might be important to explain the divergent results on their significance . thus , this study evaluated the reliability of three different questions on subjective memory complaints originating from the camdex interview . although two out of three questions on self - perception of memory deficits did not predict ad , the last question asking about memory decline noticeable by others was distinguishable even after adjustment with possible confounders , indicating the significance of particular self - reported questionnaires about subjective memory complaints when screening for ad in diabetic elderly subjects . loss of functional , but not of basic adls , proved to be predictive for having mild to moderate ad . even mild degrees of cognitive deterioration can have negative impacts on the ability to perform complex adls [ 3032 ] . these entail complex cognitive abilities that enable an individual to perform tasks that include planning , problem solving , anticipation , and inhibition of irrelevant processing . in a recent review by the committee on research of the american neuropsychiatry association , an expert panel suggested that measures of executive functions correlate strongly with functional capacities . however , clinical assessment of functional abilities in the daily life of subjects with ad is also dependent on accurate information . most instruments designed to assess instrumental adls can be influenced by the patient 's personality , mood , and cognitive status . , it should be mentioned that the capacity for self - observation is considerably preserved in patients with mild to moderate ad , although a decline in patient self - reporting on this issue is less dramatic than that seen in family reports [ 36 , 37 ] . our results indicate that among the adl disability , impaired ability to deal with medication is the most predictive for ad in both diabetic and nondiabetic individuals . besides impaired activity for travel outside familiar surroundings , shopping activity was specifically involved with ad in the diabetic participants , and financial ability in the nondiabetic subjects . shopping and managing finances are classified in the identical subdomain of functional adls that correspond to the identical staging of dementia . errors in shopping tasks are more likely to be associated with decrements in visual searching skills , selective attention , and rapid information processing . impaired attention and decreased information processing speed have been reported in aged persons with type 2 diabetes . there is a growing consensus that vascular disease may exacerbate or contribute to the manifestation of symptoms in subjects with dementia . have reported that a late - life dementia risk index , composed of age , cognitive test performance , body mass index , apolipoprotein e 4 alleles , cerebral white matter disease , ventricular enlargement , internal carotid artery thickening , history of bypass surgery , slow physical performance , and lack of alcohol consumption , can accurately stratify older adults into those with low , moderate , and high risk of developing dementia . it has been postulated that midlife high blood pressure is a risk for late - life cognitive impairment and dementia , and low diastolic pressure in older adults might be associated with the subsequent development of dementia and ad [ 43 , 44 ] . accelerated atherosclerosis and low perfusion of cerebral blood flow in diabetic elderly subjects could be implicated in a mechanism of how abnormal blood pressure affects the onset of dementia . in contrast , no predictive power for other aspects of diabetes , including hba1c level , lipid abnormalities , obesity , hypoglycemia , or treatment modality was found in the present study [ 1 , 17 ] . there were several biases in the selection of our participants , who were treated in the outpatient clinic of the kobe university hospital . they tended to have serious diabetic complications and other morbidities , while they were also motivated for treatment of their illness . despite this , our data might represent a best - case scenario for practitioners because we approached many physicians treating diabetes in aged persons . in addition , the effects of depressive mood on cognitive status were not evaluated , although patients with major depression were excluded from our participants . finally , it might be possible that cognitive normal subjects include some individuals with mild cognitive impairment , because detailed cognitive tests were not performed in the cognitive normal group . however , geriatric physicians , who were familiar to consultation of the demented disorders , asked the patients and their caregivers about their complaints on cognitive decline and the daily life function . their cognitive functions were evaluated using the mmse and a computerized test battery for ad screening . after this consultation , the advantage of screening for mild to moderate ad using this discriminating index has been clearly demonstrated in diabetic elderly subjects . second , the model for predicting ad is so succinct and easily available that nonclinical staff in outpatient clinics could administer it with ease . this would greatly improve the burden of practitioners who must face several clinical problems in elderly patients with diabetes . when considering a total scheme for detecting ad in diabetic elderly subjects , such persons can then continue to a secondary evaluation using brief cognitive tests such as the mmse and hds - r [ 5 , 6 ] and ultimately consult with specialists for dementia - related disorders . we have proposed the importance of this maneuver in prescreening for ad , using this self - reported questionnaire and including vascular risk factors in the model . the clinical relevance of this index aimed at prescreening for ad should be validated by further investigations .
background / aims . diabetes might increase the risk of alzheimer 's disease ( ad ) . for detecting dementia , it is typical to obtain informants ' perceptions of cognitive deficits , but such interviews are usually difficult in routine care . 
 we aimed to develop a model for predicting mild to moderate ad using a self - reported questionnaire and by evaluating vascular risk factors for dementia in elderly subjects with diabetes . 
 methods . 
 we recruited 286 diabetic and 155 nondiabetic elderly subjects . 
 there were 25 patients with ad and 261 cognitively normal individuals versus 30 with ad and 125 normal subjects , respectively . 
 each participant answered subjective questions on memory deficits and daily functioning . 
 information on vascular risk factors was obtained from clinical charts , and multivariate logistic regression was used to develop a model for predicting ad . results . 
 the predicted probabilities used in screening for ad in diabetic subjects constituted age , education , lower diastolic blood pressure , subjective complaints of memory dysfunction noticeable by others , and impaired medication , shopping , and travel outside a familiar locality . 
 receiver operating characteristic analysis revealed a satisfactory discrimination for ad specific for diabetic elderly subjects , with 95.2% sensitivity and 90.6% specificity . 
 conclusion . 
 this is the first useful index that can prescreen for ad in elderly subjects with diabetes .