Severe hypoglycaemia and cognitive impairment in older patients with diabetes: the Fremantle Diabetes Study

Aims/hypothesis  The aim was to investigate the relationship between severe hypoglycaemia and cognitive impairment in older patients with diabetes. Methods  A sample of 302 diabetic patients aged ≥70 years was assessed for dementia or cognitive impairment without dementia in 2001–2002 and a subsample of non-demented patients (n = 205) was followed to assess cognitive decline. A history of severe hypoglycaemia was determined from self-reports, physician assessments and records of health service use for hypoglycaemia (HSH). Prospective HSH was determined up to 2006. Data analysis, including multiple logistic and Cox regression models, was used to determine whether: (1) there were cross-sectional associations between hypoglycaemia and cognitive status, (2) historical hypoglycaemia predicted cognitive decline, and (3) baseline cognitive status predicted subsequent HSH. Results  There were significant cross-sectional associations between both cognitive impairment and dementia and hypoglycaemia. Independent risk factors for future HSH included dementia (hazard ratio 3.00, 95% CI 1.06–8.48) and inability to self-manage medications (hazard ratio 4.17, 95% CI 1.43–12.13). However, there were no significant associations between historical hypoglycaemia, incident HSH and cognitive decline. Conclusions/interpretation  Dementia is an important risk factor for hypoglycaemia requiring health service utilisation. We found no evidence that hypoglycaemia contributes to cognitive impairment in older patients with diabetes.     

The impact of diabetes mellitus on cognitive decline in the oldest of the old: a prospective population-based study

Aims/hypothesis Diabetes mellitus is a risk factor for the development of cognitive impairment and dementia in the general population up to 75 years of age. As part of the Leiden 85-plus Study we studied the effects of diabetes on cognition in the oldest old.Subjects and methods The Leiden 85-plus Study is a prospective population-based study of 599 persons from age 85 onward. Cognitive function was assessed each year from ages 85 to 90 by means of four neuropsychological tests. The presence of diabetes and vascular disease was recorded at baseline, HbA_1c was assessed by means of a blood sample at ages 85 and 90. The cross-sectional and prospective associations between diabetes and cognitive function were analysed with linear mixed models, adjusted for sex and level of education.Results At age 85, diabetes was associated with a lower level of cognitive functioning on the Letter Digit Coding test and the Stroop Test. Diabetes was not associated with accelerated cognitive decline during follow-up. Within the group of diabetic patients, macrovascular disease was the most important determinant of cognitive dysfunction.Conclusions/interpretation The association between diabetes and accelerated cognitive decline, which has been documented previously in patients up to 75 years of age, may be less evident after age 85. This suggests that the damage occurs in previous years and that therapies aimed at preventing cognitive decline and dementia should focus on the younger old.     

Update on cognitive decline and dementia in elderly patients with diabetes

AimThis article is an update of the relationship between type 2 diabetes (T2D), cognitive dysfunction and dementia in older people.Methods and resultsThe number of older patients consulting for diabetes who also exhibit cognitive difficulties is consistently growing because of the increased longevity of the population as a whole and, according to a number of studies, the increased risk of cognitive impairment and dementia in older diabetic patients. Many studies have demonstrated a link between poor glucose control and deteriorated cognitive function in diabetic patients. A history of severe hypoglycaemic episodes has also been associated with a greater risk of late-in-life cognitive deficits and dementia in patients with T2D. Several processes are thought to promote cognitive decline and dementia in diabetics. Based on both clinical and non-clinical findings, the factors most likely to alter brain function and structure are cerebrovascular complications of diabetes, alterations in glucose and insulin, and recurrent hypoglycaemia. Together with other diabetes complications, cognitive deficits contribute to functional impairment, increased frequency of depression-related symptoms, greater incidence of recurrent hypoglycaemia, poorer adherence to treatment and, finally, poorer prognosis, as evidenced by recent longitudinal studies.ConclusionClinical guidelines have recently been devised for older diabetic patients, particularly those with cognitive deficits and a reduced capacity to self-manage. In the most vulnerable patients, specific treatment strategies have been proposed for glycaemic control to limit metabolic decompensation and avoid the risk of hypoglycaemia. Educational measures, provided mainly to maintain patient autonomy and avoid hospital admission, have also been adapted according to patients’ cognitive and functional status.     

Dehydroepiandrosterone and age-related cognitive decline

In humans the circulating concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease markedly during aging, and have been implicated in age-associated cognitive decline. This has led to the hypothesis that DHEA supplementation during aging may improve memory. In rodents, a cognitive anti-aging effect of DHEA and DHEAS has been observed but it is unclear whether this effect is mediated indirectly through conversion of these steroids to estradiol. Moreover, despite the demonstration of correlations between endogenous DHEA concentrations and cognitive ability in certain human patient populations, such correlations have yet to be convincingly demonstrated during normal human aging. This review highlights important differences between rodents and primates in terms of their circulating DHEA and DHEAS concentrations, and suggests that age-related changes within the human DHEA metabolic pathway may contribute to the relative inefficacy of DHEA replacement therapies in humans. The review also highlights the value of using nonhuman primates as a pragmatic animal model for testing the therapeutic potential of DHEA for age-associate cognitive decline in humans.     

Association between diabetes mellitus and post-stroke cognitive impairment

Stroke survivors suffer from various physical, emotional, and cognitive impairments. These changes are dynamic and depend on multiple factors, including underlying diseases, baseline brain function and pathology, the site of the stroke and the post-stroke inflammation, neurogenesis as well as the subsequent remodeling of the neuro-network. First we review the structural and pathological changes of the brain in stroke survivors with diabetes mellitus, which may lead to post-stroke cognitive dysfunction. Second, we provide evidence of hyperglycemia, diabetes mellitus, hypoglycemia, and their relationship with post-stroke cognitive impairment (PSCI) and post-stroke dementia (PSD). In addition to conventional biomarkers, such as HbA1c, we also provide other novel tools to predict PSCI/PSD, such as glycemic variability, receptor for advanced glycation end products, and gut microbiota. Finally, we attempt to provide some modifying methods for glycemic control, focusing on the prevention of PSCI/PSD.     

Longitudinal associations of depressive symptoms,subjective memory decline,and cognitive functioning among Chinese older adults: Between-person and within-person perspective

ObjectivesWe examined between- and within-person associations between depressive symptoms and cognitive functioning among Chinese older adults (aged 60+) over time. Furthermore, we also investigated whether subjective memory decline (SMD) is uniquely associated with cognitive functioning above and beyond depressive symptoms for both between-person and within-person associations.MethodsAbout 7385 older adults from the China Health and Retirement Longitudinal Study reported their demographic and health status, and completed self-report measures of depressive symptoms and SMD, as well as a battery of cognitive tests, every two years at three times between 2011 and 2015.ResultsThere were significant between-person and within-person associations between depressive symptoms and cognitive functioning. Furthermore, SMD was uniquely associated with cognitive functioning for both within-person and between-person associations after controlling for depressive symptoms.ConclusionsThe results highlight the importance of careful screening and monitoring of depressive symptoms and SMD for the benefits of cognitive functioning among Chinese older adults. More importantly, SMD has practical implications for the care of Chinese older adults given significant cultural stigma attached to mental illness within Chinese culture.     

Identifying residents at greater risk for cognitive decline by Minimum Data Set in long-term care settings

Background/PurposeDementia is associated with an individual's dependency and disability, and poses a great care burden to families and societies. Neuroimaging tools and screening questionnaires are important for early diagnosis. However, factors predicting cognitive decline still remain unknown among the elder population, especially in long-term care settings.MethodsA total of 1279 residents of veteran homes in Taiwan were enrolled in this prospective study. Demographic data and items retrieved from the Minimum Data Set, including resident assessment protocols (RAPs), Minimum Data Set Cognitive Scale scores, and Resource Utilization Group-III Activities of Daily Living (RUG-III ADL) Scale scores, were analyzed. The participants were also screened using the Mini-Mental Status Examination questionnaire and assessed by the 15-item Geriatric Depression Scale.ResultsAll participants were male (mean age: 83.2 ± 5.1 years), and 9.9% developed significant cognitive decline. Obvious discrepancy in the prevalence of dementia and depression was noted between the results of screening tests and physicians' diagnosis. Participants with cancer, chronic lung disease, and poor RUG-III ADL status were at greater risk of hospitalization or death. By contrast, those with poor RUG-III ADL status, positive RAP triggers for cognitive loss/dementia, and higher sum of RAP triggers were at higher risk of developing cognitive decline.ConclusionThe diagnosis of dementia and depression remained lower than expected among the elderly population. As presented here, poor physical function, presence of RAP triggers for cognitive loss/dementia, and a higher sum of RAP triggers were strong predictors for cognitive decline.     

The association between pain and prevalent and incident motoric cognitive risk syndrome in older adults

BackgroundThe Motoric Cognitive Risk Syndrome (MCR) is a pre-dementia syndrome characterized by subjective cognitive complaints and slow gait in the absence of dementia and mobility disability. Worse cognitive and motoric function is associated with chronic pain in older adults. Our aim was to study the association between pain and prevalent and incident MCR in adults aged 65 years and older.MethodsWe analyzed the cross-sectional association between severity of pain and prevalent MCR in 3244 older adults participating in the Health and Retirement Study (2008 wave) using logistic regression analysis adjusting for demographic, peripheral, central or biological risk factors. Additionally, we analyzed the longitudinal association between severity of pain and incident MCR in 362 participants in the Central Control of Mobility in Aging Study, using Cox regression analysis.ResultsThe 155 Health and Retirement Study participants with severe pain had an increased risk of prevalent MCR (n = 249), compared to 2245 individuals without pain (adjusted for demographics OR: 2.78, 95 % CI:1.74–4.45).Over a mean follow-up of 3.01 years (SD 1.38), 29 individuals in the Central Control of Mobility in Aging Study developed incident MCR. Older adults with severe pain had over a five times increased risk of developing incident MCR, compared to those without pain even after adjusting for demographic variables (HR: 5.44, 95 % CI: 1.81–16.40).ConclusionOlder adults with severe pain have a higher prevalence and incidence of MCR. These findings should be further explored to establish if pain is a potentially modifiable risk factor to prevent cognitive decline.     

Cognitive impairment in elderly people with prediabetes or diabetes: A cross-sectional study of the NHANES population

AimTo investigate the cognitive function in people without diabetes, with prediabetes and with diabetes.Methods/DesignThe study design used was a cross-sectional analysis of data in people above 60 years registered in NHANES from 2011 to 2014.Three assessments were used to characterize cognitive function: (a) CERAD Word Learning subtest assessing immediate and delayed learning ability, (b) The Animal Fluency test assesing categorical verbal fluency, and (c) The Digit Symbol Substitution test assessing processing speed, sustained attention, and working memory.Results(A) Memory recall (−0.19, [−0.34; −0.039], p = 0.014) and Delayed memory recall decline was associated with diabetes (−0.285, [−0.503; −0.067], p = 0.01), but not in an adjusted analysis. (B) Animal Fluency score decline was associated with diabetes (−1.185, [−1.688; −0.682], p < 0.001). (C) Digit Symbol score decline was associated with diabetes (−6.897, [−8.491; −5.302], p < 0.001). Prediabetes was not associated with cognitive function.ConclusionsThis study demonstrates an association between cognitive dysfunction and diabetes. Results may also indicate that cognitive decline is not yet present in people with mild impairments of glucose homeostasis.     

Angiotensin-converting enzyme inhibitors and incidence of mild cognitive impairment. The Italian Longitudinal Study on Aging

Midlife elevated blood pressure and hypertension contribute to the development of Alzheimer's disease (AD) and overall dementia. We sought to estimate whether angiotensin-converting enzyme inhibitors (ACE-Is) reduced the risk of developing mild cognitive impairment (MCI) in cognitively normal individuals. In the Italian Longitudinal Study on Aging, we evaluated 1,445 cognitively normal individuals treated for hypertension but without congestive heart failure from a population-based sample from eight Italian municipalities with a 3.5-year follow-up. MCI was diagnosed with current clinical criteria. Dementia, AD, and vascular dementia were diagnosed based on DSM-IIIR criteria, NINCDS–ADRDA criteria, and ICD-10 codes. Among 873 hypertension-treated cognitively normal subjects, there was no significant association between continuous exposure to all ACE-Is and risk of incident MCI compared with other antihypertensive drugs [hazard ratio (HR), 0.45, 95% confidence interval (CI), 0.16–1.28]. Captopril exposure alone did not significantly modify the risk of incident MCI (HR, 1.80, 95% CI, 0.39–8.37). However, the enalapril sub-group alone (HR, 0.17, 95% CI, 0.04 –0.84) or combined with the lisinopril sub-group (HR, 0.27, 95% CI, 0.08–0.96), another ACE-I structurally related to enalapril and with similar potency, were associated with a reduced risk of incident MCI. Study duration exposure to ACE-Is as a “class” was not associated with incident MCI in older hypertensive adults. However, within-class differences linked to different chemical structures and/or drug potencies may exist, with a possible effect of the enalapril and lisinopril sub-groups in reducing the risk of incident MCI.     

Association between diabetes mellitus and post‐stroke cognitive impairment

Stroke survivors suffer from various physical, emotional, and cognitive impairments. These changes are dynamic and depend on multiple factors, including underlying diseases, baseline brain function and pathology, the site of the stroke and the post‐stroke inflammation, neurogenesis as well as the subsequent remodeling of the neuro‐network. First we review the structural and pathological changes of the brain in stroke survivors with diabetes mellitus, which may lead to post‐stroke cognitive dysfunction. Second, we provide evidence of hyperglycemia, diabetes mellitus, hypoglycemia, and their relationship with post‐stroke cognitive impairment (PSCI) and post‐stroke dementia (PSD). In addition to conventional biomarkers, such as HbA1c, we also provide other novel tools to predict PSCI/PSD, such as glycemic variability, receptor for advanced glycation end products, and gut microbiota. Finally, we attempt to provide some modifying methods for glycemic control, focusing on the prevention of PSCI/PSD.     

Effects of group work programs on community-dwelling elderly people with age-associated cognitive decline and/or mild depressive moods: A Kahoku Longitudinal Aging Study

Background:   Age-associated cognitive decline (AACD) is a predictor of dementia and highly prevalent among elderly people. Many elderly people with AACD also suffer from depressive moods. We studied, the effect of group work programs on the cognitive function and quality of life (QOL) of community-dwelling elderly people with AACD and/or mild depressive moods.
Methods:   Thirty-six subjects, with a mean age of 79.8 years, were included in this study. Twenty-one suffered from both AACD and mild depressive moods, nine suffered from mild depressive moods and six from AACD. Subjects were required to participate in a number of group work programs, such as music therapy, handicrafts and so on. They were assigned to one of two groups, and each participated in two 4-month sessions. In the first session, group 1 participated in the group work programs, while group 2 did not (control). In the second session, group 2 participated while group 1 did not. The effect of group work on elderly people with AACD ( n  = 27) and depressive moods ( n  = 31), was evaluated separately.
Results:   Improvement was observed in depressive moods and QOL (visual analogue scale of family relation, friendship and happiness, life satisfaction index) in subjects with cognitive impairment and depressive moods. The effect on cognitive function was shown only in elderly individuals suffering from depressive moods. The improvement in depressive moods and QOL seemed to be accompanied by an improvement in cognitive function but did not continue after completion of the group work program.
Conclusion:   Group work was shown to improve depressive moods, QOL and cognitive function; however, long-term effects require further examination.     

Association between mastication and cognitive status: A systematic review

PurposeA substantial number of elderly people suffer from cognitive impairment and dementia, which are considered to have various risk factors, including masticatory dysfunction; however, the association between mastication and cognition is inconclusive. The objectives of this systematic review were to provide an overview of the literature on (1) the association between mastication and cognitive function and (2) the association between mastication and dementia incidence, in elderly people.Materials and methodsSearches were conducted on five electronic databases (PubMed, EMBASE, CINHL, Cochrane Library, and Pro Quest) and publications were selected that met the following criteria: published between 2005 and 2015, written in English, and assessed associations between mastication and cognitive function, cognitive decline and dementia among population over 40 years old. The included publications were analyzed for study design, main conclusions, and strength of evidence by two reviewers who screened all abstracts and full-text articles, abstracted data and performed quality assessments by using a critical appraisal tool.ResultsA total of 33 articles (22 cross-sectional, and 11 prospective cohort studies) were evaluated. Poorer mastication was associated with lower cognitive function in 15 of the 17 cross-sectional studies and steeper decline in 5 of the 6 prospective studies. Poorer mastication was one of significant risk factors for having dementia or mild memory impairment (MMI) in 4 of 5 cross-sectional studies and for the incidence of dementia or MMI in 4 of 5 prospective studies.ConclusionsMost studies point to a positive association between mastication and cognitive function, including dementia among elderly people.     

The metabolic syndrome and 10-year cognitive and functional decline in very old men. A population-based study

ObjectivesTo describe longitudinal relationships of metabolic syndrome (MetS) to cognitive decline and functional disability in a sample of older non-institutionalized men.Methodsdata from 1991 to 2000 of the Italian cohorts of the Finland, Italy, the Netherlands, Elderly (FINE) study, were used. Global cognitive function and functional disability, defined as limitations in mobility, basic (ADLs) and instrumental activities of daily living (IADLs) were screened in 1991 and 2000. MetS was defined according to the NCEP ATP-III criteria.ResultsThe study sample consisted of 195 men, baseline age 76.1 ± 3.1 years. Baseline MetS was prospectively associated with greater 10-year cognitive and functional decline in ADLs and IADLs. After multiple adjustment including age, education, marital status, ApoE ε4 allele, cerebrovascular disease and initial cognitive and depressive status, MetS predicted cognitive decline (B = −1.684, 95%CI = −2.202 to −1.167, p < 0.001) and risk of IADLs (OR = 1.09, 95% CI = 1.01–1.20, p = 0.048) and ADLs disability (OR = 1.35, 95%CI = 1.12–1.62, p < 0.001). Interestingly, such associations were not attributable to individual altered components of MetS nor to their sum. Incident disability in ADLs and IADLs were not explained by parallel decline in cognitive function.ConclusionsMetS as an entity was associated with accelerated cognitive and functional decline in a population-based sample of very old men.     

Bidirectional association between depressive symptoms and type 2 diabetes mellitus: The China Health and Retirement Longitudinal Study

ObjectiveTo prospectively examine the bidirectional relationship between depressive symptoms and type 2 diabetes mellitus (T2DM) among middle-aged and elderly Chinese.MethodsParticipants were enrolled in 2011–2012 (Wave 1) and followed up in 2013–2014 (Wave 2) and 2015–2016 (Wave 3) in the China Health and Retirement Longitudinal Study. Depressive symptoms were evaluated by the Chinese language version of 10-item Center for Epidemiological Studies Depression Scale (CESD-10) at three waves. T2DM was assessed by biochemical biomarkers at Wave 1 and reported physician-diagnosis at Wave 2 and 3. Cox proportional hazards regression was applied to calculate hazard ratio (HR) and 95% confidence intervals (CIs) for the bidirectional association.ResultsParticipants with baseline depressive symptoms were 1.33 times as likely to develop T2DM (HR, 1.33; 95% CI: 1.06, 1.66), compared to their counterparts after adjusting for demographic characteristics and T2DM risk factors. The risk of T2DM increased linearly with higher severity of depression as determined by a higher CESD-10 score (P for trend ? 0.001). In addition, baseline T2DM was associated with increased risk of incident depressive symptoms (1.15; 1.00, 1.31) and persistent depressive symptoms (1.35; 1.03, 1.77).ConclusionThere is a positive bidirectional association between depressive symptoms and T2DM in middle-aged and elderly Chinese.     

Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services

Objective: To determine whether cognitive impairment is associated with changes in self-care behaviour and use of health and social services in older subjects with diabetes mellitus. Research design and methods: This was a community based, case-control study of subjects registered with general practices participating in the All Wales Research into Elderly (AWARE) Diabetes Study. The 396 patients aged 65 years or older with known diabetes mellitus were compared with 393 age- and sex-matched, non-diabetic controls. Adjusted odds ratio estimates of normal performance on Mini-Mental State Examination (MMSE) and Clock Drawing Test (numbers and hands) were determined. Information on self-care behaviours and use of services was obtained. Results: A total of 283 (71%) diabetic subjects scored 24 or more on MMSE, compared with 323 (88%) of controls (OR 0.54, P<0.0005). The mean (S.D.) scores were 24.5 (5.1) and 25.7 (4.3), respectively (difference between means 1.22; 95% CI 0.56, 1.88; P<0.001). Clock testing demonstrated that 257 (65%) and 286 (72%) diabetic subjects correctly placed the numbers and hands, respectively, compared with 299 (76%) and 329 (84%) of controls (OR 0.59, P<0.001 and P<0.52, P<0.0005, respectively). Both test scores declined with increasing age, earlier school leaving age and deteriorating visual acuity. Of other variables examined, only need for oral hypoglycaemic drugs or insulin, history of stroke, dementia or Parkinson's disease and symptoms of autonomic neuropathy significantly impaired one or more cognitive test scores. The odds ratios (95% CI) for normal cognitive test results in subjects with diabetes after adjusting for all significant variables was 0.74 (0.56, 0.97), P=0.029 for MMSE scores and 0.63 (0.44, 0.93), P=0.019, and 0.58 (0.38, 0.89), P=0.013, for the numbers and hands parts of the clock test, respectively. In comparison with diabetic subjects with no evidence of cognitive impairment, diabetic subjects with an MMSE score <23 were significantly less likely to be involved in diabetes self-care (P<0.001) and diabetes monitoring (P<0.001). A low MMSE score was also significantly associated with higher hospitalisation in the previous year (P=0.001), reduced ADL (activities of daily living) ability (P<0.001) and increased need for assistance in personal care (P=0.001). Conclusions: Elderly subjects with predominantly Type 2 diabetes mellitus display significant excess of cognitive dysfunction, associated with poorer ability in diabetes self-care and greater dependency. Routine screening of cognition in older subjects with diabetes is recommended.