Journal of Alzheimer's Disease - Volume 17, issue 1

Authors: Germain, Sophie | Adam, Stéphane | Olivier, Catherine | Cash, Helen | Ousset, Pierre Jean | Andrieu, Sandrine | Vellas, Bruno | Meulemans, Thierry | Reynish, Emma | Salmon, Eric | the ICTUS-EADC Network

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is characterized by a progressive deterioration of various cognitive and behavioral abilities, and it also has a health impact on the patients' caregiver. Our aim was to determine the patient (and to a lesser extent the caregiver) characteristics that contribute most to the caregiver burden. We used the baseline data from the ICTUS study, a European longitudinal cohort of patients with mild to moderate AD. Data from 1091 patients and their caregivers was used for analysis. Three principal components analyses were performed on variables from the domains of cognition, neuropsychiatric symptoms, and daily function using the MMSE …plus the ADAS-Cog, NPI, and IADL subscores, respectively. These were followed by a stepwise logistic regression to identify patient characteristics which best predict caregiver burden. The regression model (R2 = 0.35, p < 0.001) shows that the best explanatory variables are: 1) neuropsychiatric symptoms (NPI); 2) difficulties in the IADL; 3) time taken by caregiving; 4) demographic variables such as caregiver's age and patient sex; and 5) severity of cognitive impairment. In conclusion, our results demonstrate that although the strongest determinant of the caregiver burden is behavioral disturbance, the impact of the degree of cognitive impairment on burden is also significant. Show more

Keywords: Activities of daily living (ADL), Alzheimer's disease, behavioral symptoms, burden, caregiver, cognitive impairment

DOI: 10.3233/JAD-2009-1016

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 105-114, 2009

Authors: Laske, Christoph | Stellos, Konstantinos | Stransky, Elke | Leyhe, Thomas | Gawaz, Meinrad

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is characterized by massive neuronal cell loss in the brain. Granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor that promotes neuroprotective effects and supports neurogenesis in the brain. In the present study, we found significantly lower G-CSF plasma levels in 50 early AD patients in comparison with 50 age-matched healthy controls. In AD patients, G-CSF levels showed a significant inverse correlation with amyloid-β (Aβ1-42 ) levels in cerebrospinal fluid, but not with levels of tau protein in cerebrospinal fluid or Mini-Mental Status Examination scores. In addition, G-CSF plasma levels were significantly inversely correlated with age in …AD patients and healthy controls. In conclusion, decreased G-CSF plasma levels in early AD patients may contribute to a deficient hematopoietic brain support with putative pathogenic relevance. Further studies are needed to examine whether a modulation of hematopoietic growth factors such as G-CSF could be a promising new therapeutic strategy for AD. Show more

Keywords: Age, Alzheimer's disease, amyloid-β1-42, granulocyte-colony stimulating factor, plasma

DOI: 10.3233/JAD-2009-1017

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 115-123, 2009

Authors: Galimberti, Daniela | Venturelli, Eliana | Villa, Chiara | Fenoglio, Chiara | Clerici, Francesca | Marcone, Alessandra | Benussi, Luisa | Cortini, Francesca | Scalabrini, Diego | Perini, Luca | Restelli, Ilaria | Binetti, Giuliano | Cappa, Stefano | Mariani, Claudio | Bresolin, Nereo | Scarpini, Elio

Article Type: Research Article

Abstract: The distribution of the MCP-1 A-2518G single nucleotide polymorphisms (SNP) was analyzed in a population of 212 patients with frontotemporal lobar degeneration (FTLD) compared with 203 age-matched controls. A significantly decreased allelic frequency of the G allele in patients compared with controls was observed (21.1 versus 29.3%, P = 0.011, OR: 0.59, CI: 0.40–0.87). Stratifying according to gender, the association was maintained in male patients versus male controls (17.8 versus 29.4%, P = 0.016, OR = 0.46, 95% CI: 0.25–0.84), but not in female patients compared with female controls (23.5 versus 29.2%, P > 0.05). The frequency of apolipoprotein E …ε4 carriers was increased in patients (26.4 versus 13.8%, P = 0.0015, OR: 2.24, 95% CI: 1.37–3.67). Apolipoprotein E status did not influence the distribution of the A-2518G SNP. Monocyte chemotactic protein (MCP)-1 levels were determined in cerebrospinal fluid (CSF) collected from 23 patients and 17 controls. MCP-1 CSF levels were increased in patients compared with controls (449.01 ± 27.57 versus 364.19 ± 23.75 pg/ml, P = 0.011). Stratifying patients according to the presence of the polymorphic allele, significantly increased CSF MCP-1 levels were observed in carriers of the G allele compared with non-carriers (502.21 ± 44.57 versus 395.87 ± 21.92 pg/ml, P = 0.045). The MCP-1 A-2518G SNP acts as protective factor for sporadic FTLD, possibly by influencing MCP-1 production. Show more

Keywords: Cerebrospinal fluid, monocyte chemotactic protein-1, risk factor, single nucleotide polymorphism, sporadic frontotemporal lobar degeneration

DOI: 10.3233/JAD-2009-1019

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 125-133, 2009

Authors: Sohrabi, Hamid R. | Bates, Kristyn A. | Rodrigues, Mark | Taddei, Kevin | Laws, Simon M. | Lautenschlager, Nicola T. | Dhaliwal, Satvinder S. | Johnston, Amy N.B. | Mackay-Sim, Alan | Gandy, Samuel | Foster, Jonathan K. | Martins, Ralph N.

Article Type: Research Article

Abstract: Olfactory dysfunction has been reported in clinical and preclinical phases of Alzheimer's disease. Subjective memory complaints have been proposed as a potential early indicator for increased risk of Alzheimer's disease, but have also been associated with depression, personality characteristics, and health problems. In this study, we aimed to determine which of these putative markers can predict memory complaints in community-dwelling elderly individuals, focusing on olfactory symptoms. A cohort of 144 elderly volunteers (42 males and 102 females), aged 50 to 86, was recruited from an ongoing longitudinal study. Participants were assessed for olfactory capacities (threshold, discrimination, and identification), subjective memory …complaints, depression, and cognitive functions. Subjective memory complaints were significantly associated with olfactory discrimination and identification but not with threshold. Olfactory functions and depressive symptoms were both significantly associated with subjective memory complaints. In addition, memory complainers were significantly worse than non-complainers with respect to olfactory discrimination, identification, and overall olfactory functioning. The findings suggest that olfactory capacity may be a potentially significant biomarker for identifying community-dwelling elderly with memory complaints who are at increased risk for age-related cognitive decline and Alzheimer's disease. Show more

Keywords: Alzheimer's disease, cognitive decline, depression symptoms, olfactory dysfunction, smell identification, Sniffin' Sticks, subjective memory complaints

DOI: 10.3233/JAD-2009-1020

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 135-142, 2009

Authors: Lloret, Ana | Badía, Mari-Carmen | Mora, Nancy J. | Pallardó, Federico V. | Alonso, Maria-Dolores | Viña, Jose

Article Type: Research Article

Abstract: There is controversy as to whether vitamin E is beneficial in Alzheimer's disease (AD). In this study, we tested if vitamin E prevents oxidative stress and loss of cognition in AD. Fifty-seven AD patients were recruited and divided in two groups: placebo or treated with 800 IU of vitamin E per day for six months. Of these 57 patients, only 33 finished the study. We measured blood oxidized glutathione (GSSG) and used the following cognitive tests: Mini-Mental State Examination, Blessed-Dementia Scale, and Clock Drawing Test. Of those patients treated with vitaimin E, we found two groups. In the first group, …“respondents” to vitamin E, GSSG levels were lower after the treatment and scores on the cognitive tests were maintained. The second group, “non-respondents”, consisted of patients in which vitamin E was not effective in preventing oxidative stress. In these patients, cognition decreased sharply, to levels even lower than those of patients taking placebo. Based on our findings, it appears that vitamin E lowers oxidative stress in some AD patients and maintains cognitive status, however, in those in which vitamin E does not prevent oxidative stress, it is detrimental in terms of cognition. Therefore, supplementation of AD patients with vitamin E cannot be recommended without determination of its antioxidant effect in each patient. Show more

Keywords: Antioxidants, glutathione, neurodegeneration, oxidative stress, prevention

DOI: 10.3233/JAD-2009-1033

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 143-149, 2009

Authors: Grant, William B.

Article Type: Research Article

Abstract: The understanding of the role of vitamin D in maintaining optimal health has advanced sharply in the past two decades. There is mounting evidence for beneficial roles for vitamin D in reducing the risk of bone diseases and fractures, many types of cancer, bacterial and viral infections, autoimmune diseases, and cardiovascular diseases. Recently, several reports have also been published regarding the role of vitamin D in neuroprotection. This article develops the hypothesis that vitamin D can reduce the risk of developing dementia, presenting the evidence from observational and laboratory studies. The observational evidence includes that low serum 25-hydroxyvitamin D [25(OH)D] …has been associated with increased risk for cardiovascular diseases, diabetes mellitus, depression, dental caries, osteoporosis, and periodontal disease, all of which are either considered risk factors for dementia or have preceded incidence of dementia. The laboratory evidence includes several findings on the role of vitamin D in neuroprotection and reducing inflammation. Although this evidence is supportive, there do not appear to be observational studies of incidence of dementia with respect to prediagnostic serum 25(OH)D or vitamin D supplementation. Such studies now appear to be warranted. Show more

Keywords: Alzheimer's disease, cardiovascular disease, cathelicidin, periodontal disease, tooth loss, ultraviolet-B, vitamin D, vascular dementia

DOI: 10.3233/JAD-2009-1024

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 151-159, 2009

Authors: Cutuli, Debora | Foti, Francesca | Mandolesi, Laura | De Bartolo, Paola | Gelfo, Francesca | Federico, Francesca | Petrosini, Laura

Article Type: Research Article

Abstract: Since acute and chronic administration of the acetylcholinesterase inhibitors, namely donepezil, improves cognitive functions in patients afflicted by mild to moderate dementia and reverses memory deficits in experimental models of learning and memory, it seemed interesting to assess the effects of chronic donepezil treatment on cognitive functions in adult rats with forebrain cholinergic depletion. Lesions were performed by means of intracerebroventricular injections of the immunotoxin 192 IgG-saporin. The cognitive functions of lesioned animals treated or not treated with donepezil were compared with those of intact animals. Cholinergic depletion affected working memory functions, weakened procedural competencies, affected the acquisition of localizing …knowledge, and evoked remarkable compulsive and perseverative behaviors. In lesioned animals, chronic donepezil treatment ameliorated localizatory capabilities, performances linked to cognitive flexibility and procedural abilities. Furthermore, it attenuated compulsive deficits. The present data indicate positive effects of chronic donepezil treatment on specific cognitive performances, suggesting that an aimed use of acetylcholinesterase inhibitors, targeting some symptoms more than others, may be beneficial in the case of cholinergic hypofunction. The animal model used in the present research may provide an efficient method for analyzing cognition-enhancing drugs before clinical trials. Show more

Keywords: Acetylcholinesterase inhibitor, behavioral testing, cholinergic neurotransmission, cognitive flexibility, forebrain cholinergic system, 192 IgG-saporin, mnesic functions

DOI: 10.3233/JAD-2009-1040

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 161-176, 2009

Authors: De Bartolo, Paola | Gelfo, Francesca | Mandolesi, Laura | Foti, Francesca | Cutuli, Debora | Petrosini, Laura

Article Type: Research Article

Abstract: Although clinical and experimental research has demonstrated that acetylcholinesterase inhibitors, such as donepezil, are able to enhance cognitive functioning in intact subjects as well as in patients affected by different degrees of dementia, no morphological study has ever analyzed whether donepezil treatment is able to modify neocortical neuronal morphology in the intact brain and in response to cholinergic depletion. Spines (number, density, distribution) and branching (length, intersections, nodes) of apical and basal dendrites of III-layer parietal pyramidal neurons were evaluated following chronic donepezil treatment in intact animals and in animals in which the cholinergic lesion was produced by intracerebroventricular injections …of immunotoxin 192 IgG-saporin. In intact animals, the drug treatment provoked a proximal shift of spines towards the cell soma in basal dendrites. In lesioned animals, donepezil treatment reduced the upregulation of the spines induced by the cholinergic lesion in both apical and basal dendrites. Thus, while in the intact brain chronic donepezil treatment induced plastic changes in the dendritic morphology of pyramidal neurons of parietal cortex, in the presence of cholinergic depletion, it prevented the compensatory response of parietal pyramidal neurons to the loss of cholinergic inputs from basal forebrain. Show more

Keywords: Acetylcholinesterase inhibitors, cholinergic basal forebrain, 192 IgG-saporin, neuronal morphology, parietal cortex, rat

DOI: 10.3233/JAD-2009-1035

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 177-191, 2009

Authors: Rodrigues, Letícia | Biasibetti, Regina | Swarowsky, Alessandra | Leite, Marina C | Quincozes-Santos, André | Quilfeldt, Jorge A | Achaval, Matilde | Gonçalves, Carlos-Alberto

Article Type: Research Article

Abstract: Although the exact cause of Alzheimer's disease remains elusive, many possible risk factors and pathological alterations have been used in the elaboration of in vitro and in vivo models of this disease in rodents, including intracerebral infusion of streptozotocin (STZ). Using this model, we evaluated spatial cognitive deficit and neurochemical hippocampal alterations, particularly astroglial protein markers such as glial fibrillary acidic protein (GFAP) and S100B, glutathione content, nitric oxide production, and cerebrospinal fluid (CSF) S100B. In addition, prevention of these alterations by aminoguanidine administration was evaluated. Results confirm a spatial cognitive deficit and nitrative stress in this dementia model as …well as specific astroglial alterations, particularly S100B accumulation in the hippocampus and decreased CSF S100B. The hippocampal astroglial activation occurred independently of the significant alteration in GFAP content. Moreover, all these alterations were completely prevented by aminoguanidine administration, confirming the neuroprotective potential of this compound, but suggesting that nitrative stress and/or glycation may be underlying these alterations. These findings contribute to the understanding of diseases accompanied by cognitive deficits and the STZ-model of dementia. Show more

Keywords: Aminoguanidine, astrocyte, hippocampus, nitrosative stress, S100B, streptozotocin

DOI: 10.3233/JAD-2009-1034

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 193-202, 2009

Authors: Angelucci, Francesco | Bernardini, Sergio | Gravina, Paolo | Bellincampi, Lorenza | Trequattrini, Alberto | Di Iulio, Fulvia | Vanni, Diego | Federici, Giorgio | Caltagirone, Carlo | Bossù, Paola | Spalletta, Gianfranco

Article Type: Research Article

Abstract: Although the etiology of psychotic symptoms (hallucinations and delusions) in Alzheimer's disease is still not known, alterations in serotonergic neurotransmission have been proposed. In a 3-year follow-up study, we evaluated the association of serotonin (5-HT) receptor 5-HT2a 102T/C polymorphism (allelic variants CC, CT and TT) with psychotic symptom severity and response to treatment with atypical antipsychotics (risperidone, olanzapine and quietapine) in 80 patients with a diagnosis of probable Alzheimer's disease. The Neuropsychiatric Inventory (NPI) was administered to determine the frequency and severity (FxS) of psychotic and other behavioral symptoms. There was a significant difference in the NPI FxS delusion score …among the three variants of the 5-HT2a 102T/C polymorphism, with patients carrying the TT genotype the most delusional during the follow-up period. In particular, NPI FxS delusion score was higher in TT than in CC genotype at year 2. Moreover, patients with delusion symptoms carrying the CT and TT genotypes were resistant to the treatment with antipsychotic drugs. Thus our study, although at preliminary level, suggests that the presence of T allele of the 102T/C polymorphism in patients with Alzheimer's disease is associated with both increased presence of delusion symptoms and treatment-resistance to second generation antipsychotic drugs. Show more

Keywords: Alzheimer's disease, antipsychotic drugs, delusions, hallucinations, 5-HT2A receptor

DOI: 10.3233/JAD-2009-1031

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 203-211, 2009