Association between the change in heat shock protein level and cognitive function during follow-up period. ^†

<p>† Linear mixed model was tested.</p><p>Adjusted by age, gender, years of education, follow-up duration, APOE e4, hypertension, and diabetes.</p><p>Abbreviation: K-BNT = Korean version of Boston Naming Test, SVLT = Seoul Verbal Learning Test, RCFT = Rey-Complex Figure Test, COWAT = Controlled Oral Word Association Test.</p><p>Association between the change in heat shock protein level and cognitive function during follow-up period. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119180#t003fn001" target="_blank">^†</a></p

Interactive effects between time and group on change in plasma HSP levels.

<p>Repeated measure ANOVA was tested. Adjusted for age, gender, years of education, follow-up duration, APOE e4, hypertension, and diabetes (HSP70: F = 7.59 <i>p</i> = 0.008; HSP27: F = 0.67, <i>p</i> = 0.416). * <i>p</i> = 0.008.</p

Baseline characteristics of the study participants by activity participation (n = 6,647).

<p>Values are mean ± standard deviation (SD) or <i>n</i> (%).</p><p>^a Group A (participants who did not participate in any type of physical, social, and religious activity frequently), group B (participants who participated in only one type of activity frequently), group C (participants who participated in two or three types of activity frequently).</p><p>^b Analysis of variance (ANOVA) for continuous variables and <i>x</i>²-test for categorical variables.</p><p>K-IADL: Korean version of Instrumental Activities of Daily Living, MMSE-KC: Korean version of Mini Mental State Examination, SGDS-K: Korean version of 15-item Geriatric Depression Scale.</p><p>Baseline characteristics of the study participants by activity participation (n = 6,647).</p

Group classification by physical, social, and religious activity participation (<i>n</i> = 6,647).

<p>^aAt least 30 minutes per session of physical activity.</p><p>Group classification by physical, social, and religious activity participation (<i>n</i> = 6,647).</p

Flow chart of participants.

<p>Flow chart of participants.</p

Higher HbA_1c is Associated with Greater Two-Year Progression of White Matter Hyperintensities

White matter hyperintensity (WMH) lesions on brain MRI images are surrogate markers of cerebral small vessel disease (CSVD). Longitudinal studies examining the association between diabetes and WMH progression have yielded mixed results. Thus, in this study we investigated the association between HbA1c, a biomarker for the presence and severity of hyperglycemia, and longitudinal WMH change after adjusting for known risk factors for WMH progression. We recruited 64 participants from South Korean memory clinics to undergo brain MRI at the baseline and a two-year follow-up. We found: First, higher HbA1c was associated with greater global WMH volume (WMHV) changes after adjusting for known risk factors (B = 7.7E-04, p = 0.025); Second, the association between baseline WMHV and WMHV progression was only significant at diabetic levels of HbA1c (p 6.51%), and non-APOE ɛ4 carriers showed a stronger association between HbA1c and WMHV progression (B = -2.59E-03, p = 0.004); Third, associations of WMHV progression with HbA1c were particularly apparent for deep WMHV change (B = 7.17E-04, p < 0.01) compared to periventricular WMHV change, and for frontal (B = 5.00E-04, p < 0.001) and parietal (B = 1.534-04, p < 0.05) WMHV change compared to occipital and temporal WMHV change. In conclusion, higher HbA1c levels were associated with greater two-year WMHV progression, especially in non-APOE ɛ4 participants or those with diabetic levels of HbA1c. These findings demonstrate that diabetes may potentially exacerbate cerebrovascular and white matter disease.</p