03362nas a2200457 4500008004100000022001400041245015400055210006900209260001300278300001100291490000700302520203900309653000902348653002202357653001502379653001002394653002802404653002602432653001102458653001102469653001502480653003102495653000902526653001702535653002902552653001802581653001602599653001102615653001402626100002102640700002002661700002102681700002202702700002802724700002602752700002302778700002002801700002702821700002002848856003602868 2013 eng d a1534-779600aLong-term survival in adults 65 years and older with white matter hyperintensity: association with performance on the digit symbol substitution test.0 aLongterm survival in adults 65 years and older with white matter c2013 Sep a624-310 v753 a

OBJECTIVE: White matter hyperintensity (WMH) confers increased mortality risk in patients with cardiovascular diseases. However, little is known about differences in survival times among adults 65 years and older who have WMH and live in the community. To characterize the factors that may reduce mortality risk in the presence of WMH, measures of race, sex, apolipoprotein E4, neuroimaging, and cardiometabolic, physiological, and psychosocial characteristics were examined, with a particular focus on information processing as measured by the Digit Symbol Substitution Test (DSST).

METHODS: Cox proportional models were used to estimate mortality risks in a cohort of 3513 adults (74.8 years, 58% women, 84% white) with WMH (0-9 points), DSST (0-90 points), risk factor assessment in 1992 to 1994, and data on mortality and incident stroke in 2009 (median follow-up [range] = 14.2 [0.5-18.1] years).

RESULTS: WMH predicted a 48% greater mortality risk (age-adjusted hazard ratio [HR; 95% confidence interval {CI}] for WMH >3 points = 1.48 [1.35-1.62]). This association was attenuated after adjustment for DSST (HR [CI] = 1.38 [1.27-1.51]) or lacunar infarcts (HR [CI] = 1.37 [1.25,1.50]) but not after adjustment for other factors. The interaction between DSST and WMH was significant (p = .011). In fully adjusted models stratified by WMH of 3 or higher, participants with DSST greater than or equal to median had a 34% lower mortality risk among those with WMH of 3 or higher (n = 532/1217) and a 28% lower mortality risk among those with WMH lower than 3 (n = 1364/2296), compared with participants with DSST less than median (HR [95% CI] = 0.66 [0.55-0.81] and 0.72 [0.62-0.83], respectively).

CONCLUSIONS: WMH is associated with increased long-term mortality risk in community-dwelling adults 65 years and older. The increased risk is attenuated for those with higher DSST. Assessment of cognitive function with DSST may improve risk stratification of individuals with WMH.

10aAged10aApolipoprotein E410aBiomarkers10aBrain10aCardiovascular Diseases10aEpidemiologic Methods10aFemale10aHumans10aLife Style10aMagnetic Resonance Imaging10aMale10aNeuroimaging10aNeuropsychological Tests10aReaction Time10aSex Factors10aStroke10aSurvivors1 aRosano, Caterina1 aChang, Yue-Fang1 aKuller, Lewis, H1 aGuralnik, Jack, M1 aStudenski, Stephanie, A1 aAizenstein, Howard, J1 aGianaros, Peter, J1 aLopez, Oscar, L1 aLongstreth, William, T1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/610702598nas a2200205 4500008004100000022001400041245017200055210006900227260001600296520186400312100002502176700002502201700002202226700001702248700002702265700002102292700002302313700002002336856003602356 2017 eng d a1545-721400aLate-Life Depressive Symptoms as Partial Mediators in the Associations between Subclinical Cardiovascular Disease with Onset of Mild Cognitive Impairment and Dementia.0 aLateLife Depressive Symptoms as Partial Mediators in the Associa c2017 Nov 203 a

OBJECTIVE: To study whether depression contributes to the association between subclinical cardiovascular disease (CVD) and dementia, and identify the contribution's magnitude.

METHODS: Among participants from the Cardiovascular Health Study Cognition Study who did not have baseline CVD-related events (Nā€‰=ā€‰2,450), causal mediation methodology was implemented to examine whether late-life depressive symptoms, defined as 10-item Center for Epidemiologic Studies-Depression (mCES-D) Scale scores ā‰„8 from 2 to 3 years after baseline, partially mediated the association of baseline subclinical CVD (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) with mild cognitive impairment (MCI)/dementia onset occurring between 5 and 10 years from baseline. The total effect was decomposed into direct and indirect effects (via late-life depressive symptoms), obtained from an accelerated failure time model with weights derived from multivariable logistic regression of late-life depressive symptoms on subclinical CVD. Analyses were adjusted by baseline covariates: age, race, sex, poverty status, marital status, body mass index, smoking status, ApoE4 status, and mCES-D.

RESULTS: Participants contributed 20,994 person-years of follow-up with a median follow-up time of 9.4 years. Subclinical CVD was associated with 12% faster time to MCI/dementia (time ratio [TR]: 0.88; 95% CI: 0.83, 0.93). The total effect of subclinical CVD on MCI/dementia onset was decomposed into a direct effect (TR: 0.95, 95% CI: 0.92, 0.98) and indirect effect (TR: 0.92, 95% CI: 0.88, 0.97); 64.5% of the total effect was mediated by late-life depressive symptoms.

CONCLUSIONS: These data suggest late-life depressive symptoms partially mediate the association of subclinical CVD with MCI/dementia onset.

1 aArmstrong, Nicole, M1 aCarlson, Michelle, C1 aSchrack, Jennifer1 aXue, Qian-Li1 aCarnethon, Mercedes, R1 aRosano, Caterina1 aChaves, Paulo, H M1 aGross, Alden, L uhttps://chs-nhlbi.org/node/7544