CAIDE Dementia Risk Score, Alzheimer and cerebrovascular pathology: a population-based autopsy study.

BACKGROUND: CAIDE Dementia Risk Score is a tool for estimating dementia risk in the general population. Its longitudinal associations with Alzheimer or vascular neuropathology in the oldest old are not known. AIM: To explore the relationship between CAIDE Dementia Risk Score at baseline and neuritic plaques, neurofibrillary tangles, cerebral infarcts and cerebral amyloid angiopathy (CAA) after up to 10-year follow-up in the Vantaa 85 +  population. METHODS: Study population included 149 participants aged ≥85 years, without dementia at baseline, and with available clinical and autopsy data. Methenamine silver staining was used for ß-amyloid and modified Bielschowsky method for neurofibrillary tangles and neuritic plaques. Macroscopic infarcts were identified from cerebral hemispheres, brainstem and cerebellum slices. Standardized methods were used to determine microscopic infarcts, CAA and α-synuclein pathologies. The CAIDE Dementia Risk Score was calculated based on scores for age, sex, BMI, total cholesterol, systolic blood pressure, physical activity and APOEε4 carrier status (range 0-18 points). RESULTS: A CAIDE Dementia Risk Score above 11 points was associated with more cerebral infarctions up to 10 years later: OR (95% CI) was 2.10 (1.06-4.16). No associations were found with other neuropathologies. CONCLUSION: In a population of elderly aged ≥85 years, higher CAIDE Dementia Risk Score was associated with increased risk of cerebral infarcts.

Relationships between white matter hyperintensities, cerebral amyloid angiopathy and dementia in a population-based sample of the oldest old.

Previous reports suggest that brain white matter changes, a surrogate for small vessel disease, are related to cerebral amyloid angiopathy (CAA). However, this relationship has not been explored in population-based studies or in the oldest old (>85 years of age). We studied the relationships between white matter hyperintensities (WMH) determined by post-mortem magnetic resonance imaging (MRI) and neuropathologically assessed CAA in demented and nondemented subjects enrolled in the prospective community-based Finnish Vantaa 85+ Study. In this analysis, we evaluated scans and brain samples from 123 subjects (86% women) with a mean age of 90.6 years. We found CAA to be present in 63 % of the 123 subjects, whereas WMH was present in 74%, and dementia in 59 %. The presence of WMH of any severity did not relate to the presence or the degree of CAA severity, irrespective of the dementia status of the subjects. Furthermore, multivariate regression analysis showed a clear association between CAA and dementia but WMH was not related to dementia in this very old sample. We conclude that severe WMH may not be determined by CAA in this very elderly population.

Wrist-worn accelerometers in assessment of energy expenditure during intensive training.

We assessed the ability of the Polar activity recorder (AR) to measure energy expenditure (EE) during military training. Twenty-four voluntary male conscripts participated in the study and wore an AR on the non-dominant wrist 24 h a day for 7 d. The AR analyzed and stored the frequency of hand movements (f_hand) into memory at 1 min intervals. The relationship between f_hand and EE was studied over a 7 d period of military training using the doubly labeled water (DLW) technique. In addition, the relationship between f_hand and EE was analyzed during walking and running on a treadmill with an indirect calorimeter (IC), and f_hand was measured during a supervised 45 min field march test where the conscripts carried combat gear. EE was expressed as physical activity level (PAL), total energy expenditure (TEE), and activity-induced energy expenditure adjusted for body mass (AEE/BM). Over the 7 d period, f_hand alone explained 46% of inter-individual variation in PAL(DLW). After inclusion of body height and mass in the model used to predict PAL(DLW) from f_hand, a very high positive correlation and a low standard error of estimate (SEE) were observed between the AR and DLW techniques: for TEE r = 0.86 (p < 0.001), the SEE was 6.3%, and for AEE/BM r = 0.84 (p < 0.001), the SEE was 12.8%. In the treadmill exercise, f_hand correlated highly with PAL(IC) (r = 0.97 ± 0.02). In the 45 min field march test, the AR measured similar f_hand as on the treadmill at the same speed. In conclusion, the wrist-worn AR can be regarded as a reliable and valid method for assessing EE during intensive training.

Prevalence and severity of cerebral amyloid angiopathy: a population-based study on very elderly Finns (Vantaa 85+).

BACKGROUND: Cerebral amyloid angiopathy (CAA) is frequent in patients with Alzheimer's disease while its prevalence in different populations is variable. We investigated the prevalence and severity of CAA in a very elderly Finnish population. METHODS: Neuropathological investigation was performed on 306 subjects from the population-based Vantaa 85+ Study (253 women, 53 men, mean age at death 92.3 years). The presence of CAA was analysed in six brain regions by using Congo red and immunohistochemistry with an antibody against amyloid beta peptide. The severity of CAA was assessed by counting the percentage of the CAA-positive blood vessels. RESULTS: In total, 69.6% of the participants (170 women, 43 men) had CAA, with median severity of 1.0%, inter-quartile range (IQR) 0-5.4% and range 0-72.7%. CAA was more prevalent (81.1% vs. 67.2%; P = 0.046) and severe (median 2.7%, IQR 0.4-7.5%, range 0-72.7%) in the men than in the women (median 1.0%, IQR 0-4.6%, range 0-52.8%; P = 0.004). Parietal lobe showed the highest prevalence (57.8%) whereas the severity was highest (median 1.0%, IQR 0-6.0%, range 0-77%) in the frontal lobe. Prevalence of CAA in the six regions was variable, but the severity indices between those regions correlated highly (P < 0.001 for all regions). Meningeal CAA was more prevalent (69.5%) than cortical (59.3%; P < 0.001). CONCLUSION: CAA was highly prevalent, albeit mild, in the very old. The prevalence and severity of CAA were found to be highest in the frontal and parietal lobes respectively - independent of the staining method used (Congo red or amyloid beta peptide).

Aerobic fitness, energy balance, and body mass index are associated with training load assessed by activity energy expenditure.

The present study examined whether activity energy expenditure related to body mass (AEE/kg) is associated with maximal aerobic fitness (VO(2max)), energy balance, and body mass index (BMI) during the 2 hardest weeks of the military basic training season (BT). An additional purpose was to study the accuracy of the pre-filled food diary energy intake. Energy expenditure (EE) with doubly labeled water, energy intake (EI), energy balance, and mis-recording was measured from 24 male conscripts with varying VO(2max). AEE/kg was calculated as (EE x 0.9-measured basal metabolic rate)/body mass. The reported EI was lower (P<0.001) than EE (15.48 MJ/day) and mis-recording of the pre-filled diary was -20%. The negative energy balance (-6+/-26%) was non-significant; however, the variation was high. The subjects with a low VO(2max), a high BMI, and a negative energy balance were vulnerable to low AEE/kg. However, in the multivariate regression analysis only BMI remained in the model, explaining 33% of the variation in AEE/kg. During wintertime BT, AEE/kg is affected by energy balance, VO(2max), and BMI. From these three factors, overweight limits high-level training the most. Furthermore, an optimal energy balance facilitates physical performance and enables high training loads to be sustained during the BT season.

Cerebral amyloid angiopathy in a 95+ cohort: complement activation and apolipoprotein E (ApoE) genotype.

There is growing evidence that in Alzheimer's disease (AD) amyloid beta-protein (Abeta) triggers a chronic inflammatory reaction in cerebral amyloid plaques, including complement proteins. Abeta also accumulates cerebrovascularly in age- and AD-associated cerebral amyloid angiopathy (CAA). We investigated complement proteins in CAA in a population-based series using histological and immunohistochemical staining methods. The 74 subjects, aged 95 years or more, had undergone clinical neurological examination and apolipoprotein E (ApoE) genotyping. The brains had been studied for AD post-mortem, allowing us to relate the histopathological findings to clinical and genetic conditions. CAA with congophilic amyloid was found in 36/74 individuals (48.6%). The vascular amyloid deposits immunoreacted with antibodies to Abeta and complements 3d (C3d) and 9 (C9). The positivity in complement stains increased with growing severity of CAA (P = 0.001). The presence of CAA associated with ApoE epsilon4 (P = 0.0005) and overrepresentation of epsilon4 among those with moderate or severe vs. mild CAA (P = 0.03) was demonstrated. The presence of CAA associated with dementia (P = 0.01), which was contributed by both epsilon4+ (P = 0.02) and epsilon4- (P = 0.06) subjects. Our study shows that complement proteins are deposited in the affected vessels in Abeta-associated CAA. They may solely represent the cerebral Abeta- burden associated to inflammatory stimuli, or signal a contribution in the clearance of cerebral Abeta, thereby contributing to the events associated with evolution of clinical dementia. Our results demonstrate a strong association between CAA and ApoE epsilon4 as well as dementia and suggest that the contribution of CAA to dementia is largely independent of ApoE epsilon4.

HER2 oncogene amplification in extramammary Paget's disease.

AIMS: To study HER2 oncogene amplification and over-expression in skin samples of 23 patients with extramammary Paget's disease (EMP). EMP is a rare intra-epidermal adenocarcinoma, which has been reported to over-express the HER2 oncoprotein. METHODS AND RESULTS: HER2 gene amplification, detected by chromogenic in-situ hybridization, was found in 43% (10/23) of the lesions. HER2 protein over-expression (3+ immunostaining intensity) was found in 12 tumours (52%), including all 10 tumours with gene amplification. Two tumours showed low-level (2+) HER2 immunostaining. Mammary Paget's lesions, which were used as controls, showed HER2 amplification and over-expression in all 10 cases studied. CONCLUSIONS: These results indicate that HER-2 protein over-expression in EMP is common and due exclusively to gene amplification. They open up the possibility of HER2-targetted immunotherapy for patients with HER2+ disease.

Pouchitis--recurrence of the inflammatory bowel disease?

The incidence and characteristics of reservoir inflammation after restorative proctocolectomy for ulcerative colitis were studied in a series of 179 patients. The median follow up time was 27 months (range 6-80). Pouchitis occurred in 36 patients (20%) and nine of these (5%) developed a chronic, persisting pouchitis. There were no pouch failures as a result of pouchitis and no significant adverse effect on longterm functional outcome. The overall cumulative risk to develop pouchitis four years after surgery was 23%. The risk of pouchitis is unpredictable on clinical grounds except that there were significantly less patients with left sided colitis in the group who subsequently developed pouchitis. Morphological and histochemical studies showed a greater degree of colonic metaplasia in the pouch mucosa in patients with pouchitis and patients with a chronic pouchitis had the highest degree of changes. The results support the view that pouchitis is a novel manifestation of inflammatory bowel disease in ileal mucosa that has changed slowly to a colon like mucosa.