Structural brain changes and all-cause mortality in the elderly population-the mediating role of inflammation.

While MRI brain changes have been related to mortality during ageing, the role of inflammation in this relationship remains poorly understood. Hence, this study aimed to investigate the impact of MRI changes on all-cause mortality and the mediating role of cytokines. All-cause mortality was evaluated in 268 community dwelling elderly (age 65-83 years) in the MEMO study (Memory and Morbidity in Augsburg elderly). MRI markers of brain atrophy and cerebral small vessel disease (SVD), C-reactive protein (CRP) and a panel of cytokines in serum were assessed. Cox proportional hazard models were used to estimate the association of MRI changes with survival over 9 years. Regression models were used to assess the hypothesis that inflammation is mediating the relationship between MRI-brain changes and mortality. In total, 77 (29 %) deaths occurred during a mean follow up of 9 years. After adjusting for confounders, the degree of global cortical atrophy and the level of the cytokines CRP, TNF-α and IL-8 were of higher significance in study participants who had died at follow-up in comparison to survivors. In Cox proportional hazard models, higher degrees of global cortical atrophy (HR 1.56, p = 0.003) and regional atrophy of the temporal lobe (HR 1.38, p = 0.011) were associated with a significantly increased risk of mortality. Mediation analyses revealed a partial mediation by IL-6 and IL-8 of the effects of global cortical atrophy on mortality. Global cortical brain atrophy is a significant indicator of survival in the elderly. Our study supports a possible role for inflammation in the atrophy pathogenesis. If replicated in other samples, IL-6 and IL-8 level assessment may improve risk prognosis for mortality.

Functional consequences of subcortical white matter lesions and MRI-defined brain infarct in an elderly general population.

The impact of single and combined effects of subcortical white matter lesions (WMLs) and magnetic resonance imaging (MRI)-defined brain infarct on activities of daily living (ADL), depression, and health status perception was analyzed in community-dwelling elderly individuals. The study included 268 participants from the Memory and Morbidity in Augsburg Elderly (MEMO) project, a population-based study on individuals aged 65 to 83 years, conducted in Augsburg, Germany. Cerebral MRI was performed, and 2 geriatric performance tests, scales to assess ADL, depressive symptoms, and self-perceived health status were assessed. The prevalence of large (>10 mm) subcortical WML was 37.7% and of MRI-defined infarct-like lesions was 15.3%. Both vascular lesion types combined were found in 9% of the participants. Large WMLs were associated with significantly more impairments in basic ADL, inferior results in the performance tests, and a worse self-perceived health status compared to those without large WML. Magnetic resonance imaging-defined brain infarct was associated with impairments in performance tests. Participants with both lesion types were limited in all domains and were 2 to 3 times more likely to have impairments in all examined functions. Their risk of impairment in a specific function was considerably higher than the sum of the single risks associated with each lesion type alone. This study suggests that the single and especially the combined occurrence of common vascular brain lesions are associated with functional impairment. Identifying individuals with severe WML combined with MRI-defined brain infarct can help better understand the development of marked impairments in old age.

Association between cytokines and cerebral MRI changes in the aging brain.

The association between cytokines (IL-1 beta, sIL-4R, IL-6, IL-8, IL-10, IL-12, TNF-alpha) and subcortical white matter lesions, cortical atrophy and lacunar infarctions of the aging brain was investigated among 268 elderly community participants. Single pro- and anti-inflammatory cytokines were neither associated with WML nor with atrophy and lacunar infarction. An association between atrophy and the chemokine-cytokine factor (containing sIL-4R, IL-6, IL-8) remained significant after adjustment for age, gender, education, depressive symptoms, diabetes mellitus, cardiovascular diseases (stroke, TIA, myocardial infarction, myocardial insufficiency, arrhythmic heart), hypertension, body-mass index, smoking status and aggregation inhibitors as opposed to single cytokines. Atrophy of the parietal, temporal and occipital lobes was associated with the same cytokine-chemokine factor for both the whole sample or restricted to those without history of stroke/TIA. The results indicate that a combination of chemokine-cytokines rather than single cytokines may contribute to inflammatory processes associated with cortical atrophy in the aging brain.

Single and combined effects of cerebral white matter lesions and lacunar infarctions on cognitive function in an elderly population.

BACKGROUND: This study is to investigate the association between single and combined vascular brain changes (white matter lesions [WMLs], lacunar infarctions) and the cognitive domains of memory, processing speed, and motor function in the elderly adults. METHODS: In a sample of 268 participants aged 65-83 years of the MEMO (Memory and Morbidity in Augsburg Elderly) population-based study in Augsburg, Germany, cerebral magnetic resonance imaging (MRI) was performed and a detailed neuropsychological test battery applied. Analysis of covariance determined the effects of vascular brain changes on domains of cognitive functioning. RESULTS: Strong associations of large WMLs and of MRI-defined lacunar infarction with three different domains of cognitive function even after adjustment for age, gender, and education were found. The combined occurrence of both lesions affected about one in 10 participants and was associated with a strong decrease in cognitive function in all domains. The difference between the groups with only one lesion type (either large WMLs or MRI-defined infarction) and participants affected by both was significant in the domains of processing speed and memory, even after adjustment for important confounders such as age, gender, education, and comorbidities. The effects of both lesion types on cognitive function were not more than additive. CONCLUSIONS: Our study shows that both large WMLs and MRI-defined lacunar infarction contribute to impairments in different cognitive domains. The results suggest that their combined occurrence is associated with stronger reductions in cognitive function than each of the two brain lesion types alone.

Relation of cerebral small-vessel disease and brain atrophy to mild Parkinsonism in the elderly.

The association between cerebral small-vessel disease, brain atrophy, and the risk and severity of mild parkinsonian signs (MPS) remains unclear. The objective of this study is to examine the effect of lacunar brain infarcts, cerebral white matter lesions (WMLs), and cortical atrophy on the risk and severity of MPS. This study is a cross-sectional community-based cohort study comprising 268 subjects, 65 to 83 years of age, residing in the Augsburg region of southern Germany, and without contraindications for magnetic resonance imaging (MRI) of the brain. Main outcome measures. Subcortical and periventricular WMLs, lacunar brain infarcts, and cortical atrophy determined using a standardized MRI protocol developed for the Rotterdam Scan Study and an established rating scale. MPS, assessed in a standardized neurological examination and based on the Unified Parkinson's Disease Rating Scale motor scale. Lacunar brain infarcts and large subcortical white matter lesions were associated with an elevated risk of resting tremor. More severe cortical atrophy was related to an increased risk of rigidity and bradykinesia. In a linear regression analysis relating each individual MRI measurement with the severity of MPS, the number of lacunar brain infarcts and the degree of brain atrophy were correlated with the severity of resting tremor, whereas the size of subcortical and periventricular WMLs was correlated with the severity of rigidity. A higher degree of brain atrophy was associated with increased severity of either cardinal sign. In our study, presence and volume of lacunar brain infarcts, cerebral WMLs, and cortical atrophy were associated with the risk as well as severity of MPS. Determining the presence of these brain changes using brain imaging might contribute to identify persons at risk for MPS.

Relation of plasma thyroid-stimulating hormone levels to vascular lesions and atrophy of the brain in the elderly.

CONTEXT: Recent studies suggest that thyroid disease is associated with cardiovascular and peripheral vascular disease. However, little is known about the underlying pathophysiology and the relation with cerebrovascular disease or brain atrophy in the elderly. OBJECTIVE: To determine if plasma thyroid-stimulating hormone (TSH) levels are associated with vascular brain changes and cortical atrophy in the elderly. DESIGN: Community based, cross-sectional study. PARTICIPANTS AND SETTING: 268 participants of the Memory and Morbidity in Augsburg Elderly Study, 65-83 years of age and without contraindications for magnetic resonance imaging (MRI) of the brain. MAIN OUTCOME MEASURES: The presence of brain lesions and atrophy was determined using a standardized MRI protocol, an established rating scale and a single rater. Plasma TSH levels were assessed using standard laboratory methods. The association between plasma TSH levels and MRI findings was analyzed using logistic and linear regression models. RESULTS: Higher TSH levels within the normal clinical range were significantly associated with severer cortical atrophy (p = 0.04) and a higher proportion of infarct-like vascular lesions (p = 0.005) in men. These associations were independent of potential confounders, including thyroid hormone therapy, in multivariable regression analysis. No association between plasma TSH levels and both MRI outcomes were observed in women. In addition, neither in men nor in women was an association between TSH levels and white-matter lesions found. CONCLUSIONS: Increasing TSH levels even within the normal clinical range are associated with severer brain atrophy and infarct-like vascular lesions in elderly men.

Functional and cognitive consequences of silent stroke discovered using brain magnetic resonance imaging in an elderly population.

OBJECTIVES: To evaluate the prevalence of silent stroke and its associated consequences on physical, cognitive, and emotional functioning in an elderly population. DESIGN: Population-based cross-sectional survey. SETTING: The Memory and Morbidity in Augsburg Elderly project in the Augsburg region of southern Germany. PARTICIPANTS: Two hundred sixty-seven community-dwelling persons aged 65 to 83. MEASUREMENTS: The presence of silent stroke was determined using magnetic resonance imaging brain scan and a single question asking for physician-diagnosed stroke in each participant. The health effect of silent stroke was assessed using rating scales for self-perceived health status (36-item short-form health survey), activities of daily living (ADLs) and instrumental ADLs, cognitive function, and depression (Center for Epidemiologic Studies Depression scale). RESULTS: Just fewer than 13% (12.7%) of participants were affected by silent stroke. Silent stroke was associated with a history of hypertension, heart surgery, and elevated C-reactive protein. Individuals with silent stroke showed impairments on the Mini-Mental State Examination test and in the cognitive domains of memory, procedural speed, and motor performance. CONCLUSION: The presence of silent stroke has a considerable effect on cognitive performance in those affected. Determining the presence of silent stroke using brain imaging may contribute to identifying individuals at risk for developing gradual neurological deficits.