Impaired cholinergic integrity of the colon and pancreas in dementia with Lewy bodies.

Dementia with Lewy bodies is characterized by a high burden of autonomic dysfunction and Lewy pathology in peripheral organs and components of the sympathetic and parasympathetic nervous system. Parasympathetic terminals may be quantified with 18F-fluoroetoxybenzovesamicol, a PET tracer that binds to the vesicular acetylcholine transporter in cholinergic presynaptic terminals. Parasympathetic imaging may be useful for diagnostics, improving our understanding of autonomic dysfunction and for clarifying the spatiotemporal relationship of neuronal degeneration in prodromal disease. Therefore, we aimed to investigate the cholinergic parasympathetic integrity in peripheral organs and central autonomic regions of subjects with dementia with Lewy bodies and its association with subjective and objective measures of autonomic dysfunction. We hypothesized that organs with known parasympathetic innervation, especially the pancreas and colon, would have impaired cholinergic integrity. To achieve these aims, we conducted a cross-sectional comparison study including 23 newly diagnosed non-diabetic subjects with dementia with Lewy bodies (74 ± 6 years, 83% male) and 21 elderly control subjects (74 ± 6 years, 67% male). We obtained whole-body images to quantify PET uptake in peripheral organs and brain images to quantify PET uptake in regions of the brainstem and hypothalamus. Autonomic dysfunction was assessed with questionnaires and measurements of orthostatic blood pressure. Subjects with dementia with Lewy bodies displayed reduced cholinergic tracer uptake in the pancreas (32% reduction, P = 0.0003) and colon (19% reduction, P = 0.0048), but not in organs with little or no parasympathetic innervation. Tracer uptake in a region of the medulla oblongata overlapping the dorsal motor nucleus of the vagus correlated with autonomic symptoms (rs = -0.54, P = 0.0077) and changes in orthostatic blood pressure (rs = 0.76, P < 0.0001). Tracer uptake in the pedunculopontine region correlated with autonomic symptoms (rs = -0.52, P = 0.0104) and a measure of non-motor symptoms (rs = -0.47, P = 0.0230). In conclusion, our findings provide the first imaging-based evidence of impaired cholinergic integrity of the pancreas and colon in dementia with Lewy bodies. The observed changes may reflect parasympathetic denervation, implying that this process is initiated well before the point of diagnosis. The findings also support that cholinergic denervation in the brainstem contributes to dysautonomia.

Adherence to the EAT-Lancet Diet and Risk of Stroke and Stroke Subtypes: A Cohort Study.

BACKGROUND AND PURPOSE: We investigated the association between adherence to the EAT-Lancet diet, a sustainable and mostly plant-based diet, and risk of stroke and subtypes of stroke in a Danish population. For comparison, we also investigated the Alternate Healthy Eating Index-2010 (AHEI). METHODS: We used the Danish Diet, Cancer and Health cohort (n=55 016) including adults aged 50 to 64 years at baseline (1993-1997). A food frequency questionnaire was used to assess dietary intake and group participants according to adherence to the diets. Stroke cases were identified using a national registry and subsequently validated by review of medical records (n=2253). Cox proportional hazards models were used to estimate hazard ratios and 95% CIs for associations with the EAT-Lancet diet or the AHEI and risk of stroke and stroke subtypes. RESULTS: Adherence to the EAT-Lancet diet was associated with a lower risk of stroke, although not statistically significant (highest versus lowest adherence: hazard ratio, 0.91 [95% CI, 0.76-1.09]). A lower risk was observed for AHEI (0.75 [95% CI, 0.64-0.87]). For stroke subtypes, we found that adherence to the EAT-Lancet diet was associated with a lower risk of subarachnoid hemorrhage (0.30 [95% CI, 0.12-0.73]), and the AHEI was associated with a lower risk of ischemic stroke (0.76 [95% CI, 0.64-0.90]) and intracerebral hemorrhage (0.58 [95% CI, 0.36-0.93]). CONCLUSIONS: Adherence to the EAT-Lancet diet in midlife was associated with a lower risk of subarachnoid stroke, and the AHEI was associated with a lower risk of total stroke, mainly ischemic stroke and intracerebral hemorrhage.

Diabetes and Coronary Artery Disease as Risk Factors for Dementia.

AIM: Diabetes is associated with increased risk of dementia, but it is still debated to which degree this risk depends on the presence of atherosclerotic cardiovascular disease. We hypothesized that patients with diabetes and co-existing coronary artery disease (CAD), as a marker of systemic atherosclerotic cardiovascular disease, have substantially higher risk of developing dementia. METHODS: Patients ≥65 years, who underwent coronary angiography were stratified by diabetes and CAD. Outcomes were all-cause dementia, Alzheimer's dementia, and vascular dementia. We estimated adjusted hazard ratios (aHRs) using patients with neither diabetes nor CAD as a reference. RESULTS: A total of 103,859 patients were included. Of these, 23,189 (22%) had neither diabetes nor CAD, 3,876 (4%) had diabetes, 61,020 (59%) had CAD, and 15,774 (15%) had diabetes and CAD. During a median follow-up of 6.3 years, 5,592 (5.5%) patients were diagnosed with all-cause dementia. Patients with diabetes and CAD had the highest hazard rate of all-cause dementia (aHR 1.37, 95% CI 1.24-1.51), including Alzheimer's dementia (aHR 1.41, 95% CI 1.23-1.62) and vascular dementia (aHR 2.03, 95% CI 1.69-2.45). Patients with diabetes alone (aHR 1.14, 95% CI 0.97-1.33) or CAD alone (aHR 1.11, 95% CI 1.03-1.20) had a modestly increased rate of all-cause dementia. CONCLUSION: The combination of diabetes and CAD is associated with increased rate of dementia, in particular vascular dementia, suggesting that the diabetes-related risk of dementia is partly mediated through concomitant atherosclerotic cardiovascular disease. This underscores the importance of atherosclerotic cardiovascular disease prevention in diabetes patients to reduce cognitive decline.

We used national Danish healthcare registries to follow 103,859 patients examined by coronary angiography for up to 10 years to estimate the risk of dementia associated with diabetes and/or coronary artery disease. We found that diabetes and coronary artery disease are, separately, only modest risk factors of dementia. However, diabetes and coronary artery disease in combination were associated with highest risk of dementia, in particular vascular dementia. Out results suggests that the risk of dementia associated with diabetes is partly mediated through the presence atherosclerotic cardiovascular disease, which underscores the importance of atherosclerotic cardiovascular disease prevention in diabetes patients to reduce the risk of cognitive decline.

Risk and Subtypes of Stroke Following New-Onset Postoperative Atrial Fibrillation in Coronary Bypass Surgery: A Population-Based Cohort Study.

Background New-onset postoperative atrial fibrillation (POAF) develops in approximately one-third of patients undergoing cardiac surgery and is associated with a higher incidence of ischemic stroke and increased mortality. However, it remains unknown to what extent ischemic stroke events in patients with POAF are cardioembolic and whether anticoagulant therapy is indicated. We investigated the long-term risk and pathogenesis of postoperative stroke in patients undergoing coronary artery bypass grafting experiencing POAF. Methods and Results This was a register-based cohort study. Data from the WDHR (Western Denmark Heart Registry) were linked with the DNPR (Danish National Patient Register), the Danish National Prescription Register, and the Cause of Death Register. All stroke diagnoses were verified, and ischemic stroke cases were subclassified according to pathogenesis. Furthermore, investigations of all-cause mortality and the use of anticoagulation medicine for the individual patient were performed. A total of 7813 patients without a preoperative history of atrial fibrillation underwent isolated coronary artery bypass grafting between January 1, 2010, and December 31, 2018, in Western Denmark. POAF was registered in 2049 (26.2%) patients, and a postoperative ischemic stroke was registered in 195 (2.5%) of the patients. After adjustment, there was no difference in the risk of ischemic stroke (hazard ratio [HR], 1.08 [95% CI, 0.74-1.56]) or all-cause mortality (HR, 1.09 [95% CI, 0.98-1.23]) between patients who developed POAF and non-POAF patients. Although not statistically significant, patients with POAF had a higher incidence rate (IR; per 1000 patient-years) of cardioembolic stroke (IR, 1 [95% CI, 0.6-1.6] versus IR, 0.5 [95% CI, 0.3-0.8]), whereas non-POAF patients had a higher incidence rate of large-artery occlusion stroke (IR, 1.1 [95% CI, 0.8-1.5] versus IR, 0.7 [95% CI, 0.4-1.4]). Early initiation of anticoagulation medicine was not associated with a lower risk of ischemic stroke. However, patients with POAF were more likely to die of cardiovascular causes than non-POAF patients (P<0.001). Conclusions We found no difference in the adjusted risk of postoperative stroke or all-cause mortality in POAF versus non-POAF patients. Patients with POAF after coronary artery bypass grafting presented with a higher, although not significant, proportion of ischemic strokes of the cardioembolic type.