Digit Symbol Substitution Scores Research Articles

Association Between Hypertensive Disorders of Pregnancy and Interval Neurocognitive Decline: An Analysis of the Hispanic Community Health Study/Study of Latinos.

To evaluate whether hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and eclampsia, are associated with cognitive decline later in life among U.S. Hispanic/Latina individuals. The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) is a prospective population-based study of Hispanic/Latino individuals aged 18-74 years from four U.S. communities. This analysis included parous individuals aged 45 years or older who participated in the HCHS/SOL clinic study visit 1 (2008-2011) neurocognitive assessment and subsequently completed a repeat neurocognitive assessment as part of the Study of Latinos-Investigation of Neurocognitive Aging ancillary study visit 2 (2015-2018). Hypertensive disorders of pregnancy were assessed retrospectively by self-report of any gestational hypertension, preeclampsia, or eclampsia. Cognitive functioning was measured at both study visits with the Brief Spanish-English Verbal Learning Test, Digit Symbol Substitution, and Word Fluency. A regression-based approach was used to define cognitive decline at visit 2 as a function of cognition at visit 1 after adjustment for age, education, and follow-up time. Linear regression models were used to determine whether hypertensive disorders of pregnancy or their component diagnoses were associated with standardized cognitive decline after adjustment for sociodemographic characteristics, clinical and behavioral risk factors, and follow-up time. Among 3,554 individuals included in analysis, the mean age was 56.2 years, and 467 of individuals (13.4%) reported at least one hypertensive disorder of pregnancy. Individuals with hypertensive disorders of pregnancy compared with those without were more likely to have higher mean systolic blood pressure, fasting glucose, and body mass index. After an average of 7 years of follow-up, in fully adjusted models, gestational hypertension was associated with a 0.17-SD relative decline in Digit Symbol Substitution scores (95% CI, -0.31 to -0.04) but not other cognitive domains (Brief Spanish-English Verbal Learning Test or Word Fluency). Neither preeclampsia nor eclampsia was associated with neurocognitive differences. The presence of preeclampsia or eclampsia was not associated with interval neurocognitive decline. In this cohort of U.S. Hispanic/Latina individuals, gestational hypertension alone was associated with decreased processing speed and executive functioning later in life.

Elevated serum creatinine levels and risk of cognitive impairment in older adults with diabetes: a NHANES study from 2011-2014.

The brain and kidney have similar microvascular structure, which makes them susceptible to certain common pathophysiological processes. In this study, we examined several indicators of kidney injury/function associated with cognitive function in older diabetic patients in the hope of finding effective markers for detecting cognitive impairment (CI). A total of 2209 older participants (aged ≥60 years) from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) were analyzed for the association between diabetes and CI using a multiple linear regression analysis model. Using the same approach, we also analyzed the relationship between indicators of kidney injury/function and cognitive function (Animal Fluency Test, Digit Symbol Substitution Test) in the diabetic population. Diabetes was associated with CI. In age-adjusted model, older diabetics performed significantly poorer on tests of cognitive function compared to normoglycaemic individuals (1.145 points lower on the Animal Fluency Test (P = 0.005) and 7.868 points reduced on the Digit Symbol Substitution Test (P < 0.001)). In diabetics, we found elevated serum creatinine (SCr) (especially at SCr≥300uM) was associated with lower scores on cognitive function tests after strict adjustment for potential influences on cognitive function. While, albumin/creatinine ratio (ACR) was only associated with Digit Symbol Substitution score (DSS) not Animal Fluency score (AFS), and estimated glomerular filtration rate (eGFR) was only associated with CI (AFS and DSS) at the end-stage renal disease. SCr, as a sensitive indicator of kidney injury, was significantly associated with CI and can potentially be used as an effective marker for screening CI in older diabetics.

The cross‐sectional association between peripheral TNF‐∝, white matter hyperintensities, and cognitive outcomes in the HABS‐HD study

AbstractBackgroundLow‐grade inflammation appears with advance age, with the end result of an increase ratio of pro to anti‐inflammatory cytokines. Inflammatory cytokines are considered cerebrovascular disease markers, but the association of cytokine levels with poorer cognition is not conclusive. TNFα, a pro‐inflammatory cytokine, may have a role on neurodegenerative diseases, such as Alzheimer’s disease. The effect of peripheral TNFα on brain structure and cognitive outcomes in cognitively normal older adults is not well understood. A few studies have described this relationship in White cohorts, but there is a lack of research in minorities like Mexican Americans.MethodWe studied 510 cognitively normal Mexican Americans from the Health and Aging Brain Study (HABS‐HD) with signed consent, fasting blood samples, 3T MRI, clinical evaluation, and cognitive testing. TNFα was assayed via a multiple‐plex biomarker assay platform using electrochemiluminescence. White matter hyperintensities (WMH) volume was measured from FLAIR using the Statistical Parametric Mapping Lesion Segmentation Tool. Pearson correlations were used to assess the association between TNFα with WMH, global cognition (MMSE), memory (SEVLT), executive function and attention (Trails B and digit symbol substitution) measures. Linear regression was used to predict the effect of TNF‐α on WMH volume and cognitive measures. APOE4 status was assessed, and age, sex, systolic blood pressure and education were entered as covariates in the models.ResultSeventy percent of the sample were female. Sample means were 62.84 years of age, 9.94 years of education, and 137.33 for systolic blood pressure (SBP). There was not significant difference in TNFα and WMH values between APOE4 carriers and non‐carriers. TNFα had a positive significant correlation with age, education, SBP, WMH volume, and digit symbol substitution scores. Linear regression showed no association between TNFα value and WMH volume nor cognitive measures, with the exception of digit symbol substitution (B = ‐2.62; t = ‐2.03; p = 0.04).ConclusionThese results suggest TNFα peripheral values are not related to WMH volume, but were related to executive‐attention measures. Prospective studies are necessary to evaluate the use of TNFα as a potential biomarker of brain health in Mexican Americans.

Normative data for the Digit Symbol Substitution Test for diverse Hispanic/Latino adults: Results from the Study of Latinos‐Investigation of Neurocognitive Aging (SOL‐INCA)

AbstractBackgroundNeuropsychological assessment plays an important role in identifying mild cognitive impairment and dementia; demographically appropriate norms are essential for interpreting test performance and maximizing diagnostic accuracy. Limited availability of normative data for cognitive tests administered to older Hispanic/Latino adults can lead to diagnostic error. Executive functioning and information processing speed are crucial elements of neuropsychological assessment. To meet the needs of the Hispanic/Latino population, we investigated the associations of age, education, ethnic background, gender, and language on the Digit Symbol Substitution (DSS) test – a subtest of the WAIS‐R – and to provide demographically adjusted norms for a diverse group of Hispanics/Latinos.MethodThe target population for the Study of Latinos‐Investigation of Neurocognitive Aging (SOL‐INCA; 2015–2018) included individuals from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds (n = 6,172). Average age was 63.4±8.3 years, 54.5% were female, and mean education was 11.0±4.6 years. The DSS was administered as part of a larger cognitive protocol in participants’ preferred language (English or Spanish). Lower scores on the DSS are associated with slower processing speed. Demographic adjusted DSS scores, and percentile cut‐points were created using survey‐adjusted regression and quantile regression models.ResultIn covaried regression models, each year increase in age was associated with B = ‐0.54 (p&lt;0.001) units decrease in DSS scores, and each additional year of education with B = 1.42 (p&lt;0.001) units increase in performance. Males had, on average, lower DSS scores than females (B = ‐2.41; p&lt;0.001), and individuals with English as their preferred language performed better than those preferring Spanish (B = 6.18; p&lt;0.001). DSS performance varied significantly by Hispanic/Latino background with, predominantly, Mexicans scoring highest and Dominicans lowest on the DSS.ConclusionWhile other norms for Hispanic/Latino populations exist, results from this study represent the largest and only norms for Hispanic/Latinos living in the US. Representative DSS test norms for diverse groups of US‐based Hispanics/Latinos will advance cognitive assessment and the accuracy of neurocognitive disorder diagnosis in this country. We have developed an online dashboard to facilitate potential clinical use and interpretation (https://solincalab.shinyapps.io/DSST/)

Serum neurofilament light and whole brain volume associate with machine‐learning derived brain‐predicted age in the British 1946 birth cohort

AbstractBackgroundAge is the biggest risk factor for dementia, yet human brains do not age uniformly. The British 1946 birth cohort, the world’s longest continuously running birth cohort, provides a unique opportunity to assess these variations in biological ageing. So‐called ‘brain age’ is a biomarker of brain ageing, derived from machine‐learning analysis trained on a large sample of healthy brains (N=2001). Brain age has previously been related to cognitive ageing, physiological ageing and mortality risk (DOI: 10.1038/mp.2017.62), supporting the validity of this approach for assessing biological ageing.Method502 participants in the Insight 46 study, all born during one week in 1946, completed baseline cognitive and neuroimaging assessments at age 69‐71. 468 underwent combined 18florbetapir PET‐MRI scans, from which amyloid status (positive/negative), whole brain volume (WBV), total intracranial volume (TIV) and hippocampal volumes (HV) were derived. The T1‐weighted sequence was passed through the Brain‐age algorithm (https://github.com/james‐cole/brainageR), deriving brain predicted‐age (BPA) and brain‐predicted age difference (brain‐PAD; BPA minus chronological age). Serum neurofilament light (NFL) concentration was measured via Simoa immunoassay. A Preclinical Alzheimer’s Cognitive Composite Score (PACC) was calculated as a mean of z‐scores of the Mini‐mental state exam (MMSE), logical memory delayed recall, digit symbol substitution score and the Face‐Name test. Life course metrics (childhood cognitive scores, education level and Framingham Risk scores) were obtained from previous cohort assessments. Multivariate regression models were used to investigate whether life course metrics predict BPA, as well as whether NFL levels, brain volumes, or cognitive scores correlated with BPA, adjusting for chronological age.ResultThere was a significant difference between the 229 females assessed (mean BPA 65.2 years) compared with the 239 males assessed (mean BPA 70.7). BPA was independently associated with serum NFL concentration (p = 0.071) and inversely with whole brain volume (p &lt; 0.001). Life course factors did not predict brain age.ConclusionThe results showed a significant association of BPA, a cross‐sectional imaging metric, with a biochemical marker of neuronal damage (NFL) and sex. BPA has utility as an imaging metric that can integrate multiple modalities contributing to biological age, with potential as a predictive biomarker of cognitive decline.

Subjective cognitive decline is associated with neurocognition in the SOL‐INCA study

AbstractBackgroundSubjective cognitive decline (SCD) is the experience of cognitive decline not yet apparent through formal neuropsychological testing. SCD is required to meet clinical criteria for mild cognitive impairment (MCI) and is a potential early risk marker of neurocognitive changes. Despite increased risk of cognitive decline in US Hispanics/Latinos, SCD research in this group is lacking. We investigated if SCD is cross‐sectionally associated with objective neurocognitive performance in SOL‐INCA, a large community‐based sample of diverse Hispanics/Latinos.MethodParticipants (N=5,282) were age 50+ and without reported dementia. The Everyday Cognition Short Form (ECog‐12) scale measured SCD. A global score, as well as memory and executive ECog‐12 sub‐scale scores, were calculated by averaging across z‐scores of individual items assessing memory and executive functional abilities (all items were averaged for the global score). Objective neurocognitive function was measured with tests of memory (Spanish English Verbal Learning Test‐Sum and Recall scores) and executive functions (word fluency, Trail Making Test A &amp; B, and Digit Symbol Substitution scores). Memory, executive, and global neurocognitive composite scores were created by averaging across z‐scores for each cognitive domain listed above, and across all tests for the global composite. Regression models interrogated associations of ECog‐12 (global and sub‐scale scores) with their respective objective neurocognitive function counterparts (global cognition, memory, and executive function neurocognitive composite scores), adjusting for age, sex, education, Hispanic/Latino background, depression, anxiety, and cardiovascular risk factors.ResultWomen comprised 53% of the sample and 25% of the sample were age 70+. Global score, memory, and executive sub‐scale ECog‐12 scores were significantly associated with global (B= ‐0.14), memory (B= ‐0.11), and executive function (B= ‐0.11) neurocognitive composite scores respectively (all p‐values &lt;.001), such that higher ECog‐12 scores (more complaints) were related to lower neurocognition for all three neurocognitive composites.ConclusionContrary to previous research in non‐Hispanic Whites, SCD is associated with concurrent objective neurocognitive function among Hispanic/Latino community‐dwelling adults. SCD may have utility as an early risk marker in this population. More research is needed to determine the predictive value of SCD reporting within Hispanics/Latinos as well as the utility of informant’s report in predicting neurocognitive change.

Associations Between Dietary Fat Quality and Cognitive Function Among Adults: The Hispanic Community Health Study/Study of Latinos

Abstract Objectives Individual fatty acids (FA) within dietary fat classes [saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA), and trans FA (TFA)] may differentially affect risk of cognitive impairment. This has received little attention by most previous studies of diet and cognitive function, and few studies are available among Hispanic/Latinos. Our objective was to quantify associations of dietary FA (DFA) patterns with cognitive function among Hispanic/Latinos residing in the US. Methods This is a cross-sectional analysis of participants of the Hispanic Community Health Study/Study of Latinos, a diverse cohort recruited from 2008–11 (n = 7842, mean age 55 y, 62% female). Dietary data are from two 24-hr recalls; the National Cancer Institute method was used to estimate usual nutrient intake. Total animal and plant MUFA variables and 26 FA were used to derive DFA patterns by principal components analysis. Global cognitive function was calculated as the average z-score from 3 cognitive tests [Word Fluency (WF), Spanish English Verbal Learning Test (B-SEVLT) sum, and Digit Symbol Substitution (DSS)]. Survey linear regression models, were adjusted for a number of confounders including, but not limited to education, depressive symptoms, ethnicity, study site, physical activity, and total energy. Results DFA patterns were characterized by greater consumption of long-chain SFA, animal MUFA, and TFA (Factor 1); short to medium-chain SFA (Factor 2); very-long-chain PUFA (Factor 3); very-long-chain SFA, plant MUFA and essential PUFA (Factor 4). Each 1-SD increase in only Factor 2 or 4 was associated with a 0.03 ± 0.01 SD or 0.02 ± 0.01 SD higher global cognitive function score, respectively (P &amp;lt; 0.05). Factor 2 was positiviely associated with DSS and B-SEVLT scores (P &amp;lt; 0.05). Factors 1 and 4 were positively associated with DSS scores (P &amp;lt; 0.05). Factor 3 was not significantly associated with any cognitive function measure. Conclusions Our findings suggest that intake of short to medium-chain SFA, and of plant based MUFA, SFA, and PUFA, may be associated with a small benefit on global cognitive function among Hispanic/Latino adults. Null associations were observed with a very-long-chain PUFA pattern, which may be partly due to low fish consumption. Prospective studies conducted in similar and other populations are needed to confirm our results. Funding Sources None.

Diurnal blood pressure loads are associated with lower cognitive performances in controlled-hypertensive elderly individuals.

Hypertension in midlife adults is associated with cognitive decline later in life. In individuals treated for hypertension, blood pressure (BP) loads have been associated with end organ damages. This study examines whether BP load inversely correlates with performance in cognitive tasks in normotensive or controlled hypertensive (CHT) individuals. Participants between 60 and 75 years old were divided into normotensive participants who did not receive antihypertensive treatment (n = 49) and CHT patients (n = 28). They were evaluated for BP using ambulatory blood pressure monitoring and cognitive functions with tests assessing cognitive flexibility, working and episodic memory, and processing speed. Analysis of covariance between normotensive and CHT participants revealed lower cognitive performances on immediate and delayed recall and total number of words of the Rey Auditory Verbal Learning Test (P < 0.001). Spearman's correlations between BP loads and cognitive performances revealed inversed associations between diurnal systolic (SBP) loads and performances on the Trail Making Test Part B (TMTB) (P = 0.009), the TMTB-TMT Part A (P = 0.013), the Switching Cost of the color-word interference test (P = 0.020) and the Digit-Symbol Substitution Score tests (P = 0.018) in CHT. Diurnal diastolic (DBP) loads were inversely correlated to the TMTB (P = 0.014) and TMTB-TMT Part A (P = 0.006). In normotensive subjects, diurnal SBP loads were associated with the delayed recall of the Rey Auditory Verbal Learning Test (P = 0.031) and to the three components of the digit span (P < 0.05). Diurnal BP loads are associated with lower cognitive performances in CHT individuals. These results suggest a lowering of target levels of diurnal BPs and/or its variability.

Insulin resistance and cognitive test performance in elderly adults: National health and nutrition examination survey (NHANES)

ObjectivesTo examine the relationship between homeostatic model of insulin resistance (HOMA-IR) and cognitive test performance among population≥60years in a national database. HypothesisHigher insulin resistance is associated with lower cognitive test performance score in the population≥60years. ParticipantsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999–2000 and 2001–2002. MeasurementsCognitive test performance was measured by the Digit Symbol Substitution (DSS) exercise score. The main independent variable was the homeostasis model assessment of insulin resistance (HOMA-IR). We used bivariate analysis and generalized linear model adjusting for age, gender, race, education, body mass index, and systolic and diastolic blood pressures; total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride levels; and physical activity, diabetes mellitus, stroke, and congestive heart failure. STATA 14 was used to analyze the data taking into consideration the design, strata and weight. ResultsOf the 1028 participants, 44% were male and 85% were white. The mean age was 70.0±0.28 (SE) years. Their average HOMA-IR was 3.6±0.14 and they had a mean of 49.2±0.8 correct DSS score in the cognitive test. Adjusting for the confounding variables, HOMA-IR was associated with decline in DSS score (B=−0.30, 95% confidence interval=−0.54 and −0.05, p=0.01). The model explained 44% of the variability of the DSS score (R2=0.44). Significant predictors of decline in DSS score were age, gender, race, and education (p=0.01). ConclusionInsulin resistance as measured by HOMA-IR was independently associated with lower cognitive test performance score among elderly participants aged ≥60years. Longitudinal studies are needed to test the mechanism and the causal relationship.

Digit symbol substitution test score and hyperhomocysteinemia in older adults.

Mounting evidence shows that hyperhomocysteinemia is a risk factor for cognitive decline. This study enrolled subjects with normal serum levels of B12 and folate and performed thorough neuropsychological assessments to illuminate the independent role of homocysteine on cognitive functions.Participants between ages 50 and 85 were enrolled with Modified Hachinski ischemic score of <4, adequate visual and auditory acuity to allow neuropsychological testing, and good general health. Subjects with cognitive impairment resulting from secondary causes were excluded. Each of the participants completed evaluations of general intellectual function, including the Mini-Mental State Examination, Cognitive Abilities Screening Instrument, Clinical Dementia Rating, and a battery of neuropsychological assessments.This study enrolled 225 subjects (90 subjects younger than 65 years and 135 subjects aged 65 years or older). The sex proportion was similar between the 2 age groups. Years of education were significantly fewer in the elderly (7.49 ± 5.40 years) than in the young (9.76 ± 4.39 years, P = 0.001). There was no significant difference in body mass index or levels of vitamin B12 and folate between the 2 age groups. Homocysteine levels were significantly higher in the elderly group compared to the younger group (10.8 ± 2.7 vs. 9.5 ± 2.5 μmol/L, respectively, P = 0.0006). After adjusting for age, sex, and education, only the Digit Symbol Substitution (DSS) score was significantly lower in subjects with hyperhomocysteinemia (homocysteine >12 μmol/L) than those with homocysteine ≤12 μmol/L in the elderly group (DSS score: 7.1 ± 2.7 and 9.0 ± 3.0, respectively, beta = −1.6, 95% confidence interval [CI] = −2.8∼−0.5, P = 0.001) and borderline significance was noted in the combined age group (beta = −1.1, 95% CI = −2.1∼−0.1, P = 0.04). We did not find an association between hyperhomocysteinemia and other neuropsychological assessments.This is the first study to demonstrate a significant association between hyperhomocysteinemia (>12 μmol/L) and low DSS score, suggesting that DSS score may be an independent marker of cognitive impairment in response to hyperhomocysteinemia, especially in the elderly. Further replication studies with larger cohorts are needed to confirm our results.

Effects of Sleep Deprivation on Hypoglycemia-Induced Cognitive Impairment and Recovery in Adults With Type 1 Diabetes.

To ascertain whether hypoglycemia in association with sleep deprivation causes greater cognitive dysfunction than hypoglycemia alone and protracts cognitive recovery after normoglycemia is restored. Fourteen adults with type 1 diabetes underwent a hyperinsulinemic, hypoglycemic clamp on two separate occasions. Before one glucose clamp, the participants stayed awake overnight to induce sleep deprivation. Participants were randomized and counterbalanced to the experimental condition. Cognitive function tests were performed before and during hypoglycemia and for 90 min after restoration of normoglycemia. Cognitive impairment during hypoglycemia did not differ significantly between the sleep-deprived and non-sleep-deprived conditions. However, in the sleep-deprived state, digit symbol substitution scores and choice reaction times were significantly poorer during recovery (P < 0.001) and hypoglycemia symptom scores were significantly higher (P < 0.001), even when symptoms that may have been caused by sleep deprivation, such as tiredness, were removed. Hypoglycemia per se produced a significant decrement in cognitive function; coexisting sleep deprivation did not have an additive effect. However, after restoration of normoglycemia, preceding sleep deprivation was associated with persistence of hypoglycemic symptoms and greater and more prolonged cognitive dysfunction during the recovery period.

Association Between Vestibular and Cognitive Function in U.S. Adults: Data From the National Health and Nutrition Examination Survey.

Vestibular function declines with age, and emerging evidence suggests that vestibular loss is associated with cognitive impairment. Whether vestibular dysfunction is associated with age-related cognitive decline is unknown. We used data from the 1999-2002 National Health and Nutrition Examination Surveys to evaluate the influence of vestibular function on cognitive performance in a nationally representative sample of U.S. adults aged ≥60 years (n = 1,303). Vestibular function was measured with the modified Romberg test, and cognitive function was measured by the digit symbol substitution (DSS) score test. We also developed structural equation models (SEMs) to explore whether vestibular dysfunction and associated cognitive impairment mediate the effect of age on falls and activities of daily living (ADL) difficulty. Vestibular dysfunction was present in 58% of the study population. In multivariate analyses, vestibular dysfunction was associated with a 3.4-point lower DSS score (95% confidence interval: -5.2, -1.6; p < .0001), equivalent to the effect of 5 years of age. Vestibular dysfunction was also associated with a significantly higher odds of ADL difficulty (p = .001), and with a 2.6-fold increase in the odds of falling (p = .017). SEMs suggested that vestibular function mediates 14.3% of the effect of age on cognitive performance. Further SEMs suggested that lower cognitive performance mediates the association between vestibular loss and ADL difficulty as well as falls. This study suggests that vestibular dysfunction partially mediates the association between age and cognitive impairment. Moreover, the cognitive impairment that results from vestibular loss may contribute to ADL difficulty and falls in older individuals.

Effect of renal impairment on cognitive function during a 3-year follow up in elderly patients with type 2 diabetes: Association with microinflammation.

We investigated the effect of renal impairment on cognitive function during a 3-year follow up in elderly type 2 diabetic patients, and an association with microinflammation. Four cognitive function tests - Mini-Mental State Examination (MMSE), word recall, Digit Symbol Substitution (DSS) and Stroop Color Word - were carried out in 67 patients. Renal impairment was defined as the presence of albuminuria and a decline in estimated glomerular filtration (eGFR) <60mL/min/1.73m(2). Inflammatory markers, such as highly sensitive C-reactive protein (hs-CRP), tumor necrotizing factor-α (TNF-α), interleukin (IL)-1β and IL-6, were measured at baseline. At baseline, cognitive decline was found in patients with renal impairment. The DSS test was independently associated with eGFR decline, whereas MMSE tended to be associated with albuminuria after adjusting for confounding factors. Regarding changes in cognitive function and renal impairment, changes in urinary albumin to creatinine ratios were strongly and independently associated with changes in word recall scores. In patients with persistent eGFR decline, there was a tendency toward a greater decrease in MMSE and DSS scores, whereas in those with newly detected albuminuria, there was a tendency toward a greater decrease in word recall scores. Increased baseline levels of hs-CRP, TNF-α and IL-6 were associated with renal impairment and cognitive function, especially DSS tests, respectively. However, the increased levels were not independent predictors for cognitive decline. The present study showed a reciprocal relationship between cognitive decline and renal impairment, especially progression of albuminuria. Thus, monitoring treatment using renal biomarkers will be important for preserving both renal and cognitive function.

Cross-sectional associations of oral health measures with cognitive function in late middle–aged adults: A community-based study

It has not been established to what extent oral health is associated with cognitive function in late middle-aged adults. In this study, which is part of the national Atherosclerosis Risk in Communities (ARIC) study, the authors investigated whether tooth loss and periodontitis are associated with lower cognitive function.The authors analyzed ARIC data measuring cognitive function in 11,097 participants from 1996 through 1998 according to tests of delayed word recall, digit-symbol substitution (DSS) and word fluency; 9,874 participants answered dental screening questions. Of the 8,554 dentate participants, 5,942 received oral examinations. The authors used measures of dental status, number of teeth and periodontitis (classified according to the Biofilm-Gingival Interface Index) in multiple linear regression models to estimate these factors' cross-sectional association with cognitive scores, adjusting for sociodemographic factors, cigarette smoking, alcohol use and diabetes.Approximately 13 percent of participants were edentulous. Of the dentate participants, 27.3 percent had fewer than 20 teeth and 12.4 percent had pocket depth of 4 millimeters or more with severe bleeding. Compared with dentate participants, edentulous participants had lower scores for all cognitive tests. Among the dentate participants, having fewer teeth and gingival bleeding were associated with lower DSS and word fluency test scores, although periodontal pocket depth was not.In this cohort, edentulism was correlated with lower cognitive status. Tooth loss and gingival bleeding were markers of poorer executive function among dentate people. Practical Implications. The association of lower cognitive scores with edentulism suggests that past oral diseases may be a risk indicator for cognitive decline, whereas the association with gingival inflammation indicates a possible effect of cognitive decline on oral health. Practitioners should be aware that both current and historical markers of oral disease might be associated with decline in cognitive function, even in adults of late middle age.

Cognitive Decline and Oral Health in Middle-aged Adults in the ARIC Study

Even before dementia becomes apparent, cognitive decline may contribute to deterioration in oral health. This cohort study of middle-aged adults evaluated associations of six-year change in cognitive function with oral health behaviors and conditions in the Atherosclerosis Risk in Communities (ARIC) study. Cognitive function was measured at study visits in 1990-1992 and 1996-1998 with three tests: (a) Delayed Word Recall (DWR), (b) Digit Symbol Substitution (DSS), and (c) Word Fluency (WF). Cognitive decline scores were computed as ‘studentized’ residuals of 1996-1998 scores regressed against 1990-1992 scores. In 1996-1998, 10,050 participants answered dental screening questions, and 5,878 of 8,782 dentate participants received a comprehensive oral examination. Multiple regression models used cognitive change to predict oral health behaviors and conditions with adjustment for covariates. In the fully adjusted models, greater decline in all three measures of cognitive function was associated with increased odds of complete tooth loss. Greater decline in DSS and WF scores was associated with infrequent toothbrushing. Decline in WF scores was also associated with higher plaque levels. In these middle-aged adults, six-year cognitive decline was modestly associated with less frequent toothbrushing, plaque deposit, and greater odds of edentulism, but not with other oral behaviors or diseases.

Association of Chronic Kidney Disease and Cerebral Small Vessel Disease with Cognitive Impairment in Elderly Patients with Type 2 Diabetes

Background/Aims: In recent years, the relationship between chronic kidney disease (CKD) and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD) is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients. Methods: Seventy-nine type 2 diabetic patients (mean age, 76.0 years) were enrolled in the present study. CKD was defined as the presence of albuminuria and/or a low estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m²). SVD was evaluated by the presence and severity of silent brain infarcts (SBIs) and white matter lesions (WMLs) on brain magnetic resonance imaging. Neuropsychological tests were assessed using four validated cognitive instruments. Results: In multiple linear regression analyses, albuminuria was associated with worse modified Stroop Color Word scores (β = 0.284, p = 0.017) and low eGFR was associated with reduced Digit Symbol Substitution scores (β = -0.224, p = 0.026) after adjustment for age, sex, education years, diabetes duration, hypertension, multiple SBIs, and advanced WMLs. In contrast, there were no significant associations between CKD markers and Mini-Mental State Examination or Word Recall scores. Conclusion: Our findings suggest that albuminuria and low eGFR are associated with frontal lobe dysfunction independently of SVD in elderly type 2 diabetic patients.

Lower Digit Symbol Substitution Score in the Oldest Old is Related to Magnetization Transfer and Diffusion Tensor Imaging of the White Matter

Background: Slowing information processing is common among community-dwelling elderly and it predicts greater mortality and disability risk. Slowing information processing is related to brain macro-structural abnormalities. Specifically, greater global atrophy and greater small vessel disease of the white matter (WM) have been associated with slower processing speed. However, community-dwelling elderly with such macro-structural abnormalities can maintain processing speed. The roles of brain micro-structure for slow processing in very old adults living in the community is uncertain, as epidemiological studies relating these brain markers to cognition and in the context of other health characteristics are sparse. Hypothesis: Information processing is cross-sectionally associated with WM micro-structure independent of overt macro-structural abnormalities and also independent of health related characteristics. Methods: Imaging indices of micro-structure diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), macro-structure white matter hyperintensities (WMH), gray matter (GM) volume, digit symbol substitution test (DSST), and health characteristics were measured in 272 elderly (mean age 83 years old, 43% men, 40% black) living in the community. Results: The DTI- and MTI-indices of micro-structure from the normal appearing WM and not from the normal appearing GM were associated with DSST score independent of WMH and GM volumes. Associations were also independent of age, race, gender, mini-mental score, systolic blood pressure, and prevalent myocardial infarction. Interpretation: DTI and MTI-indices of normal appearing WM are indicators of information processing speed in this cohort of very old adults living in the community. Since processing slowing is a potent index of mortality and disability, these indices may serve as biomarkers in prevention or treatment trials of disability.

Bispectral Index Monitoring during Sedation with Sevoflurane, Midazolam, and Propofol

Bispectral Index (BIS) has been used to measure sedation depth. Ideally, to guide anesthetic management, range of BIS scores at different sedation levels should not overlap, and BIS should be independent of drug used. This study assessed ability of BIS to predict sedation depth between sevoflurane, propofol, and midazolam. Quality of recovery was also compared. Patients undergoing surgery with local or regional anesthesia and sedation were randomized to sevoflurane (n = 23), midazolam (n = 21), or propofol (n = 22). Sedation was titrated to Observers's Assessment of Alertness-Sedation score of 3 (responds slowly to voice). BIS and Observers's Assessment of Alertness-Sedation were measured every 5 min. BIS prediction probability (PK) was compared between drugs. Recovery was assessed by BIS and Digit Symbol Substitution and memory tests. Bispectral Index of responders to voice was significantly different from nonresponders (86 +/- 10 vs. 74 +/- 14, mean +/- SD; P < 0.001) However, wide variability and overlap in BIS were observed (25th-75th percentile, responders vs. non-responders: 79-96 vs. 65-83). BIS of responders was different for sevoflurane versus propofol and midazolam. BIS was a better predictor of propofol sedation than sevoflurane or midazolam (PK = 0.87 +/- 0.11, 0.76 +/- 0.01, and 0.69 +/- 0.02, respectively; P < 0.05). At 10 min after the procedure, 76, 48, and 24% of sevoflurane, propofol, midazolam patients, respectively, returned to baseline Digit Symbol Substitution scores (P < 0.05). Excitement-disinhibition occurred in 70, 36, and 5% of sevoflurane, propofol, and midazolam patients, respectively (P < 0.05). Individual BIS scores demonstrate significant variability, making it difficult to predict sedation depth. The relation between BIS and sedation depth may not be independent of anesthetic agent. Quality of recovery was similar between drugs, but excitement occurred frequently with sevoflurane.

Neuropsychological and Pharmacokinetic Assessment of Hospice Inpatients Receiving Morphine

Eighteen inpatients receiving morphine for cancer pain in a palliative care unit were recruited to a study employing a range of neuropsychological tests to assess cognitive function. The tests employed were National Adult Reading Test, Williams Delayed Recall Test, Immediate Memory for Digits, Trailing Making Test, and the Digit Symbol Substitution Test. These data were correlated with biochemical tests of renal and hepatic function, morphine dose, route of administration, plasma morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations. Despite having no clinical evidence of impairment of cognitive function, the level of current intellectual functioning (Symbol Digit Substitution Test) was on average two standard deviations below normal. Immediate memory appeared to be well preserved, but Delayed Recall and Trailing Making Test scores were significantly above normal. There was no significant correlation between morphine dose, or plasma morphine and M3G and M6G concentrations, and the neuropsychological test results, although a weak correlation was found between plasma morphine concentration and digits forward ( r = −0.47, p < 0.05) and Digit Symbol Substitution scores ( r = −0.46, p < 0.05). Seven patients had some degree of nausea or vomiting, ascribed as an opioid adverse effect, and had higher serum creatinine concentrations, worse neuropsychological performance, and significantly higher plasma M3G concentrations ( p < 0.05). These data provide some evidence to suggest that cognitive functioning in patients with advanced cancer receiving morphine may be significantly impaired despite apparent clinical normality. From these data it is not possible to determine what relative causal contribution the disease and the drug made to these observations, although renal function, plasma morphine, and M3G concentrations may be important. Future research should address a broad range of neuropsychological testing to assist in the modification of practices aimed at enhancement of quality of life, such as opioid substitution or rotation.

Reduced awareness of hypoglycaemia in the elderly despite an intact counter-regulatory response

We investigated awareness of hypoglycaemia and its counter-regulatory hormone response in six young (ages 24-49, mean 30 years) and seven elderly (ages 65-80, mean 72 years) healthy non-diabetic subjects. A hyperinsulinaemic glucose clamp was used to control blood glucose level on two separate occasions. During the hypoglycaemic study, blood glucose was lowered in a stepwise manner to plateaus of 3.5, 3.0 and 2.5 mmol/l. A symptom score, visual reaction time test and digit symbol substitution test was completed pre-study, and at the end of each plateau. Pulse rate, blood pressure and counter-regulatory hormone measurements were taken every 15-30 min. The euglycaemic study was identical except that blood glucose remained at the fasting level. During hypoglycaemia, the elderly group had lower symptom scores than the young group (total relative score at glucose 2.5 mmol/l, mean +/- SEM: elderly -1 +/- 2.5, young 23 +/- 6.7, p < 0.01) and fewer individual symptoms despite a similar counter-regulatory hormone response. There was no difference in deterioration of the visual reaction times or digit symbol substitution scores during hypoglycaemia between the age groups. Unlike the young group, the elderly subjects had no tachycardia in response to hypoglycaemia. Their reduced awareness of hypoglycaemia may be due to an impaired end-organ response to counter-regulatory hormones, resulting in fewer symptoms.