Wolfgang Krampla

Conversion from cognitive health to mild cognitive impairment and Alzheimer's disease: Prediction by plasma amyloid beta 42, medial temporal lobe atrophy and homocysteine

The changes of plasma amyloid beta (Abeta42) protein, homocysteine and medial temporal lobe atrophy (MTA) were studied by the transition from cognitive health to mild cognitive impairment (MCI) and to Alzheimers disease (AD) in a prospective cohort of individuals aged 75 years. MTA but not plasma Abeta42 measured at baseline predicted which persons remained cognitively healthy (CH) and who developed AD 2.5 years later. The increase of plasma Abeta42 over time significantly distinguished between persons who remained CH on the one hand and MCI converters and AD converters out of cognitive health on the other (CH-to-MCI and CH-to-AD converters). Although both groups showed similar increase of Abeta42 levels, CH-to-AD converters had a higher increase of homocysteine compared to CH-to-MCI converters or to persons remaining CH. In comparison to all cognitive subgroups, the AD converters from MCI at baseline showed the smallest increase of Abeta42 levels and rather no increase of homocysteine. In logistic regression analysis, the increase of plasma Abeta42 but not change of MTA significantly predicted the conversion from CH to MCI, and changes of MTA and homocysteine but not of plasma Abeta42 predicted the conversion from CH to AD. The increase of plasma Abeta42 correctly allocated CH-to-MCI and CH-to-AD converters with low (63%) specificity (for both) and low (60%) sensitivity (54% for AD group). These results indicate that (1) plasma Abeta42 alone is not suitable as a biomarker for AD, (2) in the course of cognitive deterioration of the AD-type the increase of plasma Abeta42 seems to be an initial event, (3) similar to cerebrospinal fluid, changes of plasma Abeta42 may reflect the transition from cognitive health to AD, and (4) whether persons with MCI develop AD may depend on an accumulation of further toxic metabolites such as homocysteine.

Plasma Amyloid Beta-42 Independently Predicts Both Late-Onset Depression and Alzheimer Disease

OBJECTIVES Depression in the elderly might represent a prodromal phase of Alzheimer disease (AD). High levels of plasma amyloid beta-42 (Aβ42) were found in prestages of AD and also in depressed patients in cross-sectional studies. This study examined the association of emerging late-onset depression (LOD) and AD with plasma Aβ42 in a sample of never depressed and not demented persons at baseline. DESIGN Prospective 5-year longitudinal study. PARTICIPANTS A community dwelling of older adults (N = 331) from the Vienna Transdanube Aging study. MEASUREMENTS Laboratory measurements, cognitive functioning, and depressive symptoms were assessed at baseline, 2.5, and 5 years follow-ups. RESULTS After exclusion of converters to AD, regression analysis revealed that higher plasma Aβ42 at baseline was a positive predictor for conversion to first episode of LOD. Independent of whether persons with mild cognitive impairment (MCI) at 2.5 years were included or excluded into regressions, higher plasma Aβ42 at baseline was a significant predictor for the development of probable or possible AD at 5 years. Higher conversion to AD was also associated with male gender but not with either higher scores on the Geriatric Depression Scale (GDS), with stroke or cerebral infarction nor apolipoprotein E ε4 allele. No association was found for an interaction between plasma Aβ42 levels and GDS. CONCLUSIONS Higher plasma Aβ42 at baseline predicted the development of first episode of LOD and conversion to probable or possible AD. Emerging depression as measured by scores on GDS at the 2.5-year follow-up, either alone or as an interaction factor with plasma Aβ42, failed to predict the conversion to AD at 5 years.

Plasma amyloid β protein 42 in non-demented persons aged 75 years: Effects of concomitant medication and medial temporal lobe atrophy

Plasma amyloid beta (Abeta42) levels increase with age and are elevated in some patients during the early stages of Alzheimers disease (AD). Although plasma Abeta42 is not useful for diagnosis of AD, it might be a biological risk factor. In the elderly population a considerable variety of concomitant medication is used for the treatment of various disorders. How this co-medication might influence Abeta42 levels is still to be investigated. Through the Vienna Transdanube Aging study (VITA), the authors measured cross-sectional Abeta42 plasma levels during the initial examination of 526 individuals aged 75 years without dementia. The medication considered included: treatment with calcium channel blockers, digitalis, anticoagulants, antihistamines, ergotamine, histamine H(2) receptor antagonists, bronchodilators, pentoxyfilline, neuroleptics, insulin, oral antidiabetics, l-dopa, benzodiazepines, oestrogen, Gingko biloba, vitamins, piracetam, non-steroidal anti-inflammatory drugs (NSAIDs), and statins. Of the study population aged 75 years, 90% were users of some of the above-mentioned medication. Depending on their medial temporal lobe atrophy (MTA), users of insulin showed significantly increased levels of Abeta42, while users of gingko biloba for at least 2 years of drug intake had significantly decreased Abeta42 plasma levels, independent of their MTA. Users of NSAIDs showed a non-significant trend to reduced Abeta42 plasma levels, while users of biguanides showed an increase in Abeta42 plasma levels. In the multiple regression analysis considering possible interactions between various medications statin users showed a significant decrease of Abeta42; insulin users had again significantly higher and long-term gingko biloba users lower plasma Abeta42 levels. Persons with a low degree of MTA had significantly increased Abeta42 plasma levels. Considering the increase of Abeta42 plasma levels as a risk factor for AD, any changes induced by medication by long-term use in the peripheral and possibly also in the central compartment, could be of clinical relevance.

Data From the VITA Study Do Not Support the Concept of Vascular Depression

OBJECTIVE Cerebrovascular lesions that are apparent in magnetic resonance scans and regioselective atrophy of the brain have been proposed as a causative or exacerbating factor in depression with late-life onset. The objective of this study was to investigate whether deep white matter or periventricular hyperintensities, small ischemic lesions, and brain atrophy contribute to late-onset depression in the nondemented elderly. METHOD Based on a group of 606 individuals of identical age (75.8 years, standard deviation: 0.45 years) residing in two districts of Vienna, the authors built a case-control cohort (ratio: 1:4) consisting of 51 individuals with late-onset major or minor depression matched with 204 subjects of identical gender and education status without depression, resulting in two groups that were homogenous with respect to age, place of residence, gender, and education. Scores for focal brain lesions, mediotemporal lobe atrophy, and ventricular enlargement as well as risk factors for vascular disease were compared with cognition and depression status. RESULTS Depressed individuals had significantly lower scores than nondepressed subjects in all measures of cognitive and executive function. No significant relation was found between a diagnosis of depression and any type of discrete brain lesions, but measures of brain atrophy (Cella Media indices, mediotemporal atrophy) showed a clear statistical relation to depression. No relationship was found between depression and lipid parameters. CONCLUSION The authors found no indication that white matter hyperintensities or minor ischemic lesions played a role in our depressed cohort, casting doubt on the vascular hypothesis of late-onset depression.

Conversion from mild cognitive impairment to dementia: Influence of folic acid and vitamin B12 use in the vita cohort

ObjectiveIncreased serum homocysteine and low folate levels are associated with a higher rate of conversion to dementia. This study examined the influence of vitamin B12/folic acid intake on the conversion from mild cognitive impairment (MCI) to dementia.ParticipantsA community dwelling cohort of older adults (N=81) from the Vienna Transdanube aging study with MCI.DesignProspective study with a retrospective evaluation of vitamin intake.MeasurementsLaboratory measurements, brain magnetic resonance imaging, and cognitive functioning were assessed at baseline and at five-year follow-up.ResultsThe self-reported combined use of folic acid and vitamin B12 for more than one year was associated with a lower conversion rate to dementia. Serum levels of homocysteine and vitamin B12 as measured at baseline or at five years were not associated with conversion. Higher folate levels at baseline in females predicted a lower conversion rate to dementia. The assessment of brain morphological parameters by magnetic resonance imaging revealed higher serum folate at baseline, predicting lower medial temporal lobe atrophy and higher levels of homocysteine at baseline, predicting moderate/severe global brain atrophy at five years. Users of vitamin B12 or folate, independent of time and pattern of use, had lower grades of periventricular hyperintensities and lower grades of deep white matter lesions as compared to non-users.ConclusionsThese results from a middle european study support observations on the protective ability of folate in MCI patients with respect to conversion to dementia; they also point to a participation of homocysteine metabolism on processes associated with brain atrophy.

Risk Factors for Alzheimer Dementia in a Community-Based Birth Cohort at the Age of 75 Years

Background: Few prospective community-based cohort studies have so far concentrated specifically on the risk factors for Alzheimer dementia (AD) with onset after the age of 75 years. Methods: We prospectively investigated a birth cohort of 585 nondemented inhabitants in the area on the East bank of the river Danube who were born between 1925 and 1926. They were investigated at the age of 75 years and followed up after 30 months. The follow-up was possible with 488 probands; 36 died, and 61 refused to participate. Results: In multivariate analysis an elevated risk for late-onset AD could be found for (1) history of depressive episodes (OR = 2.09; 95% CI = 1.25–3.48); (2) the Ε4 allele of the APOE gene (OR = 1.86; 95% CI = 1.08–3.23); (3) lower serum level of folate (OR = 0.92; 95% CI = 0.87–0.98); (4) no chronic use of nonsteroidal anti-inflammatory drugs (OR = 0.40; 95% CI = 0.20–0.81), and (5) lower education (OR = 1.43; 95% CI = 1.03–2.00). Conclusions: Five risk factors for late-onset AD could be confirmed, which might be targets for preventive strategies.

High cortisol and low folate are the only routine blood tests predicting probable Alzheimer's disease after age 75-results of the Vienna Transdanube Aging Study.

low on the dementia knowledge questionnaire expressed interest in further dementia education. These results suggest that the lack of initiative to seek help observed in the Chinese-American immigrant community may not be entirely due to a low level of knowledge about the illness. Alternative reasons could include a deficiency of appropriate Chinese-language educational materials or a lack of awareness about dementia health services. When presented with easily accessible educational opportunities to learn about dementia, Chinese-American immigrants are willing to participate, so it is important that individuals in this ethnic community be given appropriate resources to correct their misconceptions about dementia, leading to early recognition of its symptoms and the use of treatments and services.

Disproportionate subarachnoid space hydrocephalus—outcome and perivascular space

We sought to identify the prevalence of MRI features of disproportionately enlarged subarachnoid space hydrocephalus in possible idiopathic normal pressure hydrocephalus (DESH‐iNPH) and to describe the clinico‐radiological features and outcomes of a community‐based investigation (The Vienna Trans‐Danube Aging study).

MRI features of Binswanger's disease predict prognosis and associated pathology.

To identify the prevalence of MRI features of Binswangers disease (BD), specifically MRI with diffuse white matter lesions and scattered multiple lacunes (BD‐MRI), and to describe neurological features and pathological outcomes of a community‐based cohort study.

Reduction in Serum Aquaporin-4 Antibody Titers During Development of a Tumor-Like Brain Lesion in a Patient With Neuromyelitis Optica: A Serum Antibody–Consuming Effect?

Abstract Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the CNS with severe involvement of the optic nerve and spinal cord. Highly specific serum IgG autoantibodies (NMO-IgG) that react with aquaporin-4 (AQP4), the most abundant CNS water channel protein, are found in patients with NMO. However, in vivo evidence combining the results of AQP4 antibody serum levels and brain pathology is lacking. We report a patient with NMO whose AQP4 antibody levels decreased simultaneously with clinical deterioration caused by the development of a tumor-like brain lesion. In the seminecrotic biopsied brain lesion, there was activated complement complex, whereas only very scattered immunoreactivity to AQP4 protein was detectable. The decrease in serum AQP4 antibody levels and the loss of AQP4 in the tumor-like lesion could represent a “serum antibody–consuming effect” during lesion formation.