Journal of Alzheimer's Disease - Volume 25, issue 4

Authors: Förster, Stefan | Buschert, Verena C. | Buchholz, Hans-Georg | Teipel, Stefan J. | Friese, Uwe | Zach, Christian | la Fougere, Christian | Rominger, Axel | Drzezga, Alexander | Hampel, Harald | Bartenstein, Peter | Buerger, Katharina

Article Type: Research Article

Abstract: The effect of cognitive intervention on brain metabolism in Alzheimer's disease (AD) is largely unexplored. Therefore, we aimed to investigate clinical cognitive parameters and 18 FDG PET to test for effects of a cognitive intervention in patients with amnestic mild cognitive impairment (aMCI) or mild AD. Patients with aMCI (n = 24) or mild AD (n = 15) were randomly assigned either to cognitive intervention groups (IGs), receiving weekly sessions of group-based multicomponent cognitive intervention, or active control groups (CGs), receiving pencil-paper exercises for self-study. We obtained resting-state FDG-PET scans and neuropsychological testing at baseline and after six-months. Normalized FDG-PET …images were analyzed using voxel-based SPM5 approaches to determine longitudinal changes, group-by-time interactions, and correlations with neuropsychological outcome parameters. Primary global cognitive outcome was determined by analyses of covariance with MMSE and ADAS-cog scores as dependent measures. Both, aMCI and AD subgroups of CGs showed widespread bilateral cortical declines in FDG uptake, while the AD subgroup of IGs showed discrete decline or rather no decline in case of the aMCI subgroup. Group by time analyses revealed strongest attenuation of metabolic decline in the aMCI subgroup of the IGs, involving left superior temporal- and anterior cingulate gyrus. However, correlation analyses revealed only weak non-significant associations between increased FDG uptake and improvement in primary or secondary outcome parameters. Concurrently, there was significant improvement in global cognitive status in the aMCI subgroup of the IGs. A six-month cognitive intervention imparted cognitive benefits in patients with aMCI, which were concurrent with an attenuated decline of glucose metabolism in cortical regions affected by neurodegenerative AD. Show more

Keywords: Alzheimer's disease, cognitive intervention, cognitive stimulation, cognitive training, FDG PET, mild cognitive impairment

DOI: 10.3233/JAD-2011-100996

Citation: Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 695-706, 2011

Authors: Riley, Kathryn P. | Jicha, Gregory A. | Davis, Daron | Abner, Erin L. | Cooper, Gregory E. | Stiles, Nancy | Smith, Charles D. | Kryscio, Richard J. | Nelson, Peter T. | Van Eldik, Linda J. | Schmitt, Frederick A.

Article Type: Research Article

Abstract: Preclinical Alzheimer's disease (pAD) reflects neuropathological findings of AD in cognitively normal subjects. The present study represents an effort to determine if differences could be identified in the longitudinal patterns of cognitive performance in persons classified as pAD compared to those who did not meet criteria for AD at autopsy. We included 121 subjects who were cognitively normal from baseline through their last assessment before death and who underwent autopsy. Participants were classified into two groups: pathologically normal (PN; NIA-Reagan low or no-likelihood of AD, n = 89) and preclinical AD (pAD; NIA-Reagan criteria of intermediate or high-likelihood of AD …in the absence of clinical dementia symptoms, n = 32) followed for a mean 7.5 years prior to death. Longitudinal rates and patterns of change in scores on a standard cognitive battery were compared between these two groups. While cognitive results at baseline and last evaluations revealed no clear cross sectional group differences after adjustment for age, ApoE status, education, and gender, statistically significant differences between the pAD and PN groups in slope of decline were seen on a composite score of cognitive function. Further analyses showed three components of this score reached significance: constructional praxis, delayed recall of a word list, and category verbal fluency. Despite being clinically viewed as normal at enrollment and at the final exam, there are significant differences in rates of cognitive decline in participants classified as pAD compared to those without this pathology. Longitudinal changes in slope of decline in specific cognitive test measures can serve as non-invasive methods for the detection of pAD. Show more

Keywords: Alzheimer's disease, cognition, normal, preclinical

DOI: 10.3233/JAD-2011-102133

Citation: Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 707-717, 2011

Authors: Silvestrini, Mauro | Viticchi, Giovanna | Falsetti, Lorenzo | Balucani, Clotilde | Vernieri, Fabrizio | Cerqua, Raffaella | Luzzi, Simona | Bartolini, Marco | Provinciali, Leandro

Article Type: Research Article

Abstract: The aim of this 12-month prospective study was to establish whether severe internal carotid artery stenosis is associated with faster progression of the cognitive impairment in patients with Alzheimer's disease (AD). Four hundred and eleven patients with AD underwent extracranial carotid Doppler ultrasound evaluation. Cerebrovascular reactivity to hypercapnia was measured by means of the breath-holding index (BHI) in those with severe carotid artery stenosis using transcranial Doppler ultrasonography. Cognitive status was quantified with the Mini Mental State Evaluation (MMSE). Ninety-eight patients had severe carotid artery stenosis, 41 right (group 1), and 57 left (group 2), while 313 had no significant …stenosis (group 3). Group 1 and 2 patients showed an increased probability compared with group 3 patients to develop severe dementia (MMSE scores < 21) during the 12-month follow-up period: OR 2.36 (95% CI: 1.14–4.87) and OR 4.90 (95% CI: 2.65–9.04), respectively (p < 0.05, multiple logistic regression analysis). A BHI value ipsilateral to the stenosis < 0.69 predicted a worse MMSE score at 12 months irrespective of the side of the stenosis. These findings suggest that severe internal carotid artery stenosis can be considered as a marker of a faster rate of progression of the cognitive decline in AD. They also indicate that cerebral hemodynamic evaluation could be applied to identify patients at higher risk of rapid cognitive decline, who may benefit from aggressive treatment, and warrant investigation of the advantages of carotid revascularization procedures in these patients. Show more

Keywords: Alzheimer's disease, carotid stenosis, cerebrovascular disease

DOI: 10.3233/JAD-2011-101968

Citation: Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 719-726, 2011

Authors: Arranz, Lorena | De Castro, Nuria M. | Baeza, Isabel | Giménez-Llort, Lydia | De la Fuente, Mónica

Article Type: Research Article

Abstract: We have previously shown that 3xTgAD mice (triple-transgenic mice for Alzheimer's disease, harboring PS1M146V , AβPPSwe , tauP301L transgenes) suffer detrimental changes in some key lymphocyte functions, described as health and longevity markers, with males being more affected than females and showing higher mortality rates. In the present work, 3xTgAD and wild type 129/C57BL6 male and female non- and environmentally enriched mice were used. The enriched environment (EE) began in the adulthood (6 months) and lasted for 5.5 months. The animals were sacrificed at advanced stages of the disease (15 month-old), and spleen, thymus, and plasma were obtained. The …results indicate that 3xTg-AD males are especially benefitted from EE exposure, as shown by the improvement in lymphocyte functional activities such as chemotaxis and natural killer cytotoxicity, as well as in plasma corticosterone levels. By contrast, wild type females seem to be highly sensitive to EE removal, as regards the proliferation capacity of lymphocytes and their intracellular glutathione content. These results support the relevance of gender differences in AD when screening for new strategies for the control of the disease, and suggest that active life, by means of EE, should be maintained until natural death in order to preserve all the positive effects that this strategy exerts on the immune system. Show more

Keywords: Alzheimer's disease, environmental enrichment, immune senescence, 3xTg-AD mice

DOI: 10.3233/JAD-2011-110236

Citation: Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 727-737, 2011

Authors: Zimmermann, Rüdiger | Lelental, Natalia | Ganslandt, Oliver | Maler, Juan Manuel | Kornhuber, Johannes | Lewczuk, Piotr

Article Type: Research Article

Abstract: Preanalytical sample handling and storage procedures play an extremely important role in reliably measuring neurochemical dementia diagnostics (NDD) biomarkers: Aβ1-40 , Aβ1-42 , Tau, and pTau181. To test different handling and storage conditions, the following protocols were applied: (a) storage at room temperature for one week, (b) deep-freezing and thawing up to three cycles, (c) deep-freezing, thawing and keeping under +4°C for two days before the analysis, and (d) long-term stability of a deeply frozen sample. Between the first and the seventh day of the storage at room temperature, the percentage of the concentrations (compared to the starting concentrations) fluctuated: …104.3–105.3, 97.6–93.2, 100.6–96.8, and 97.9–90.2 for Aβ1-40 , Aβ1-42 , Tau, and pTau181, respectively. Re-freezing cycles resulted in the percentage fluctuations of the concentrations: 101.1–105.5, 95.4–99.7, 98.3–100.0, and 100.5–101.4 for Aβ1-40 , Aβ1-42 , Tau, and pTau181, respectively. Keeping previously frozen/thawed samples under +4°C for two days resulted in the percentage differences of the concentrations: +15.9, +2.2, −1.1, and −0.1 for Aβ1-40 , Aβ1-42 , Tau, and pTau181, respectively. During long-term stability, the coefficients of linear correlation (R2 ) were: Aβ1-40 , 0.007; Aβ1-42 , 0.02; Tau, 0.011; and pTau181, 0.02, and the corresponding inter-assay coefficients of variation: 13.9%, 13.9%, 11.0%, and 10.7% for Aβ1-40 , Aβ1-42 , Tau, and pTau181, respectively. We conclude that the NDD biomarkers are relatively stable when the cerebrospinal fluid sample is kept at room temperature for about four days; one or two thawing/refreezing cycles do not profoundly affect the biomarkers concentrations, however three cycles result in increased unsystematic variation. The four biomarkers seem to be stable in a sample stored deeply frozen for more than two years. Show more

Keywords: Alzheimer's disease, amyloid-β, cerebrospinal fluid, laboratory quality control, preanalytical sample handling, Tau

DOI: 10.3233/JAD-2011-110212

Citation: Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 739-745, 2011

Authors: Koval, Lyudmyla | Lykhmus, Olena | Kalashnyk, Olena | Bachinskaya, Nataliya | Kravtsova, Ganna | Soldatkina, Mariya | Zouridakis, Marios | Stergiou, Christos | Tzartos, Socrates | Tsetlin, Victor | Komisarenko, Sergiy | Skok, Maryna

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is characterized by a loss of α4β2 and α7 nicotinic acetylcholine receptors (nAChRs) in the brain and severe memory impairments. Previously, we found that antibodies elicited against extracellular domain of α7 nAChR subunit decreased the number of α7 nAChRs in the brains of mice and impaired episodic memory. Here we show that antibodies capable to bind α7(1-208) are present in the blood of both healthy humans and AD patients. In healthy individuals, their capacity to compete with [125 -I]-α-bungarotoxin for the binding to α7(1-208) increased with age. The level of such antibodies was significantly elevated in children …with severe form of obstructive bronchitis and in mice injected with Lewis lung carcinoma cells expressing both α4β2 and α7 nAChRs. Elevated antibody levels were accompanied with decreased surface nAChRs on the blood lymphocytes of children and of mice immunized with α7(1-208). Among AD patients, the level of α7 nAChR-specific antibodies was significantly larger in people 62.5 ± 1.5 years old with moderate or severe AD stages (15.2 ± 1.3 MMSE scores) compared to those of 76 ± 1.5 years old with the mild (22.7 ± 0.1 MMSE scores) AD stage. We concluded that α7(1-208) nAChR-specific antibodies found in the human blood are formed as a result of common infections accompanied with the destruction of respiratory epithelium. Elevated blood plasma levels of α7(1-208) nAChR-specific antibodies are characteristic for the early-onset AD and, therefore, are suggested as one of the risk factors for the development of this form of the disease. Show more

Keywords: Autoantibodies, blood, early-onset Alzheimer's disease, nicotinic acetylcholine receptor, obstructive bronchitis

DOI: 10.3233/JAD-2011-101845

Citation: Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 747-761, 2011

Article Type: Correction

DOI: 10.3233/JAD-2011-1440

Citation: Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 763-763, 2011

Article Type: Other

DOI: 10.3233/JAD-2011-110213

Citation: Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 765-767, 2011