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Sample records for alzheimers disease patients

  1. Fungal infection in patients with Alzheimer's disease.

    PubMed

    Alonso, Ruth; Pisa, Diana; Marina, Ana Isabel; Morato, Esperanza; Rábano, Alberto; Carrasco, Luis

    2014-01-01

    Alzheimer's disease is a progressive neurodegenerative disorder that leads to dementia mainly among the elderly. This disease is characterized by the presence in the brain of amyloid plaques and neurofibrillary tangles that provoke neuronal cell death, vascular dysfunction, and inflammatory processes. In the present work, we have analyzed the existence of fungal infection in Alzheimer's disease patients. A proteomic analysis provides compelling evidence for the existence of fungal proteins in brain samples from Alzheimer's disease patients. Furthermore, PCR analysis reveals a variety of fungal species in these samples, dependent on the patient and the tissue tested. DNA sequencing demonstrated that several fungal species can be found in brain samples. Together, these results show that fungal macromolecules can be detected in brain from Alzheimer's disease patients. To our knowledge these findings represent the first evidence that fungal infection is detectable in brain samples from Alzheimer's disease patients. The possibility that this may represent a risk factor or may contribute to the etiological cause of Alzheimer's disease is discussed.

  2. Current treatments for patients with Alzheimer disease.

    PubMed

    Osborn, Gerald G; Saunders, Amanda Vaughn

    2010-09-01

    There is neither proven effective prevention for Alzheimer disease nor a cure for patients with this disorder. Nevertheless, a spectrum of biopsychosocial therapeutic measures is available for slowing progression of the illness and enhancing quality of life for patients. These measures include a range of educational, psychological, social, and behavioral interventions that remain fundamental to effective care. Also available are a number of pharmacologic treatments, including prescription medications approved by the US Food and Drug Administration for Alzheimer disease, "off-label" uses of medications to manage target symptoms, and controversial complementary therapies. Physicians must make the earliest possible diagnosis to use these treatments most effectively. Physicians' goals should be to educate patients and their caregivers, to plan long-term care options, to maximally manage concurrent illnesses, to slow and ameliorate the most disabling symptoms, and to preserve effective functioning for as long as possible. The authors review the various current treatments for patients with Alzheimer disease.

  3. Emotional Working Memory in Alzheimer's Disease Patients

    PubMed Central

    Satler, Corina; Tomaz, Carlos

    2011-01-01

    Background Few studies have assessed whether emotional content affects processes supporting working memory in Alzheimer disease (AD) patients. Methods We assessed 22 AD patients and 40 elderly controls (EC) with a delayed matching and non-matching to sample task (DMST/DNMST), and a spatial-delayed recognition span task (SRST; unique/varied) using emotional stimuli. Results AD patients showed decreased performance on both tasks compared with EC. With regard to the valence of the stimuli, we did not observe significant performance differences between groups in the DMST/DNMST. However, both groups remembered a larger number of negative than positive or neutral pictures on unique SRST. Conclusion The results suggest that AD patients show a relative preservation of working memory for emotional information, particularly for negative stimuli. PMID:22163239

  4. Immune blood biomarkers of Alzheimer disease patients.

    PubMed

    Avagyan, Hripsime; Goldenson, Ben; Tse, Eric; Masoumi, Ava; Porter, Verna; Wiedau-Pazos, Martina; Sayre, James; Ong, Reno; Mahanian, Michelle; Koo, Patrick; Bae, Susan; Micic, Miodrag; Liu, Philip T; Rosenthal, Mark J; Fiala, Milan

    2009-05-29

    Alzheimer disease (AD) patients have an impairment of anti-amyloid-beta (Abeta) innate immunity and a defect in immune gene transcription [Fiala, M., Liu, P.T., Espinosa-Jeffrey, A., Rosenthal, M.J., Bernard, G., Ringman, J.M., Sayre, J., Zhang, L., Zaghi, J., Dejbakhsh, S., Chiang, B., Hui, J., Mahanian, M., Baghaee, A., Hong, P., Cashman, J., 2007b. Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcumin. Proc. Natl. Acad. Sci. U. S. A. 104, 12849-12854]. Early diagnosis is a cornerstone of preventive approaches to AD. Phospho-tau and Abeta CSF levels are useful markers of neurodegeneration but not of a process leading to neurodegeneration. To detect an early biomarker of AD, we developed a flow cytometric test of Abeta phagocytosis, which was 94% positive (<400 MFI units) in AD patients (mean age+/-SEM 77+2.2 years; mean score+/-SEM 198.6+/-25.5 MFI units) and 60% positive in MCI patients (77+/-5.6 years; 301+/-106 MFI units). Control subjects, active senior university professors, were 100% negative (74.2+/-4.2 years; 1348+/-174 MFI units). The test had a low specificity in older caregivers and older amyotrophic lateral sclerosis (ALS) patients. We also tested transcriptional regulation of the genes MGAT-III and Toll-like receptor-3 in macrophages. Macrophages of "Type I" patients (a majority of patients) showed gene down regulation at baseline and up regulation by curcuminoids; macrophages of "Type II" patients showed opposite responses. The results of flow cytometric testing suggest that normal Abeta phagocytosis is associated with healthy cognition and lesser risk of AD. The significance of abnormal results in aged persons should be investigated by prospective studies to determine the risk of AD.

  5. Voluntary Imitation in Alzheimer's Disease Patients.

    PubMed

    Bisio, Ambra; Casteran, Matthieu; Ballay, Yves; Manckoundia, Patrick; Mourey, France; Pozzo, Thierry

    2016-01-01

    Although Alzheimer's disease (AD) primarily manifests as cognitive deficits, the implicit sensorimotor processes that underlie social interactions, such as automatic imitation, seem to be preserved in mild and moderate stages of the disease, as is the ability to communicate with other persons. Nevertheless, when AD patients face more challenging tasks, which do not rely on automatic processes but on explicit voluntary mechanisms and require the patient to pay attention to external events, the cognitive deficits resulting from the disease might negatively affect patients' behavior. The aim of the present study was to investigate whether voluntary motor imitation, i.e., a volitional mechanism that involves observing another person's action and translating this perception into one's own action, was affected in patients with AD. Further, we tested whether this ability was modulated by the nature of the observed stimulus by comparing the ability to reproduce the kinematic features of a human demonstrator with that of a computerized-stimulus. AD patients showed an intact ability to reproduce the velocity of the observed movements, particularly when the stimulus was a human agent. This result suggests that high-level cognitive processes involved in voluntary imitation might be preserved in mild and moderate stages of AD and that voluntary imitation abilities might benefit from the implicit interpersonal communication established between the patient and the human demonstrator.

  6. Alzheimer's disease.

    PubMed

    Scheltens, Philip; Blennow, Kaj; Breteler, Monique M B; de Strooper, Bart; Frisoni, Giovanni B; Salloway, Stephen; Van der Flier, Wiesje Maria

    2016-07-30

    Although the prevalence of dementia continues to increase worldwide, incidence in the western world might have decreased as a result of better vascular care and improved brain health. Alzheimer's disease, the most prevalent cause of dementia, is still defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality as proposed in the original amyloid hypothesis. Age-related, protective, and disease-promoting factors probably interact with the core mechanisms of the disease. Amyloid β42, and tau proteins are established core cerebrospinal biomarkers; novel candidate biomarkers include amyloid β oligomers and synaptic markers. MRI and fluorodeoxyglucose PET are established imaging techniques for diagnosis of Alzheimer's disease. Amyloid PET is gaining traction in the clinical arena, but validity and cost-effectiveness remain to be established. Tau PET might offer new insights and be of great help in differential diagnosis and selection of patients for trials. In the search for understanding the disease mechanism and keys to treatment, research is moving increasingly into the earliest phase of disease. Preclinical Alzheimer's disease is defined as biomarker evidence of Alzheimer's pathological changes in cognitively healthy individuals. Patients with subjective cognitive decline have been identified as a useful population in whom to look for preclinical Alzheimer's disease. Moderately positive results for interventions targeting several lifestyle factors in non-demented elderly patients and moderately positive interim results for lowering amyloid in pre-dementia Alzheimer's disease suggest that, ultimately, there will be a future in which specific anti-Alzheimer's therapy will be combined with lifestyle interventions targeting general brain health to jointly combat the disease. In this Seminar, we discuss the main developments in Alzheimer's research.

  7. [Neuroimaging for patients with Alzheimer disease in routine practice].

    PubMed

    Matsuda, Hiroshi

    2010-07-01

    In routine practice neuroimaging has been applied as an adjunct technique for early and differential diagnosis of Alzheimer disease in routine practice. Of the several neuroimaging modalities, magnetic resonance imaging (MRI) and brain perfusion single-photon emission computed tomography (SPECT) have been commonly used in Japan; further software programs are used to aid statistical analysis of the imaging results. For example voxel-based specific regional analysis system for Alzheimer disease (VSRAD) for MRI and easy Z-score imaging system (eZIS) are used for the analysis of MRI and SPECT. In the early stage of Alzheimer disease, specific findings of regional atrophy and perfusion reduction are observed in some areas. In the posterior cingulate gyrus precuneus and parietal cortex, perfusion reduction was more frequently observed than atrophy. On the other hand, in the medial temporal structures, perfusion reduction was less frequently observed than atrophy. Perfusion reduction in the the posterior cingulate gyrus precuneus and in the parietal cortex was more prominent in the case of patients with early-onset Alzheimer disease than in the case of patients with late-onset Alzheimer disease. Further, atrophy in the medial temporal structures was more prominent in the case of patients with late-onset Alzheimer disease than in the case of those with early-onset Alzheimer disease. These findings are helpful for differentiating of Alzheimer disease from other diseases characterized by dementia.

  8. Sexual Concerns of Male Spouses of Female Alzheimer's Disease Patients.

    ERIC Educational Resources Information Center

    Litz, Brett T.; And Others

    1990-01-01

    Presents case study which highlights attendant cognitive changes that occur in Alzheimer's patient, presenting caregiver with challenges to couple's sexual functioning. Describes man who reported erectile dysfunction directly stemming from stressful changes that had occurred in his relationship to his wife who had Alzheimer's disease. General…

  9. Alzheimer disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000760.htm Alzheimer disease To use the sharing features on this page, ... of brain function that occurs with certain diseases. Alzheimer disease is one form of dementia. It affects memory, ...

  10. Weak central coherence in patients with Alzheimer's disease(•).

    PubMed

    Mårdh, Selina

    2013-03-15

    Central coherence refers to the ability to interpret details of information into a whole. To date, the concept of central coherence is mainly used in research of autism, Asperger's syndrome and recently in the research on eating disorders. The main purpose of the present study was to examine central coherence in patients with Alzheimer's disease. Nine Alzheimer's disease patients and ten age- and gender-matched control subjects, who differed significantly in neurological assessment, were shown a picture of a fire. Compared to control subjects, the Alzheimer's disease patients described the picture in a fragmented way by mentioning details and separate objects without perceiving the context of the fire. In conclusion, patients with Alzheimer's disease are at the weak end of central coherence, and hence suffer from a fragmented view of their surroundings. The findings have important clinical implications for the understanding of patients with Alzheimer's diseaseand also for the possibility of caregivers to meet the Alzheimer's disease individual in an appropriate way in the everyday care.

  11. Changes in Semantic Memory in Early Stage Alzheimer's Disease Patients.

    ERIC Educational Resources Information Center

    Weingartner, Herbert J.; And Others

    1993-01-01

    Contrasts changes in semantic memory in elderly normal controls and Alzheimer's disease (AD) patients before patients expressed symptoms. Found that controls generated more uncommon exemplars from closed semantic categories (fruits and vegetables) than did AD patients prior to presumed onset of AD. AD patients were just as productive as controls…

  12. Clinical aspects of Alzheimer's disease in black and white patients.

    PubMed Central

    Hargrave, R.; Stoeklin, M.; Haan, M.; Reed, B.

    1998-01-01

    This article examines the association between ethnicity and psychiatric symptoms in patients with Alzheimer's disease. Data from a cross-sectional study of patients evaluated at nine California Department of Health Alzheimer's Disease Diagnostic and Treatment Centers (ADDTCs) were used. Using the ADDTC patient database, sociodemographic and clinical variables in 207 black patients and 1818 white patients with probable and possible Alzheimer's disease were compared. Logistic and linear regression analysis indicated the following results: 1) black patients had fewer years of education and more often had hypertension, 2) black patients reported shorter duration of illness at the time of initial diagnosis of dementia, 3) black patients had lower Mini-Mental State Examination scores and higher Blessed Roth Dementia Rating Scale scores at the time of initial diagnosis, and 4) black patients more frequently reported insomnia and less frequently reported anxiety. Additional studies are needed to validate these findings and to generate hypotheses about the role of cardiovascular disease and pathophysiology of psychiatric symptoms in ethnic populations with Alzheimer's disease. PMID:9510621

  13. Investigational medications for treatment of patients with Alzheimer disease.

    PubMed

    Potter, Pamela E

    2010-09-01

    Development of effective treatments for patients with Alzheimer disease has been challenging. Currently approved treatments include acetylcholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine hydrochloride. To investigate treatments in development for patients with Alzheimer disease, the author conducted a review of the literature. New approaches for treatment or prevention focus on several general areas, including cholinergic receptor agonists, drugs to decrease β-amyloid and tau levels, antiinflammatory agents, drugs to increase nitric oxide and cyclic guanosine monophosphate levels, and substances to reduce cell death or promote cellular regeneration. The author focuses on medications currently in clinical trials. Cholinergic agents include orthostatic and allosteric muscarinic M1 agonists and nicotinic receptor agonists. Investigational agents that target β-amyloid include vaccines, antibodies, and inhibitors of β-amyloid production. Anti-inflammatory agents, including nonsteroidal anti-inflammatory drugs, the natural product curcumin, and the tumor necrosis factor α inhibitor etanercept, have also been studied. Some drugs currently approved for other uses may also show promise for treatment of patients with Alzheimer disease. Results of clinical trials with many of these investigational drugs have been disappointing, perhaps because of their use with patients in advanced stages of Alzheimer disease. Effective treatment may need to begin earlier-before neurodegeneration becomes severe enough for symptoms to appear.

  14. Semantic Priming for Coordinate Distant Concepts in Alzheimer's Disease Patients

    ERIC Educational Resources Information Center

    Perri, R.; Zannino, G. D.; Caltagirone, C.; Carlesimo, G. A.

    2011-01-01

    Semantic priming paradigms have been used to investigate semantic knowledge in patients with Alzheimer's disease (AD). While priming effects produced by prime-target pairs with associative relatedness reflect processes at both lexical and semantic levels, priming effects produced by words that are semantically related but not associated should…

  15. Memantine-associated hyperkalaemia in a patient with Alzheimer's disease.

    PubMed

    Tsukamoto, Tatsuo; Yamada, Hidetaka; Uchimura, Naohisa

    2013-09-01

    Memantine is an N-methyl-D-aspartate glutamate receptor antagonist that may improve cognitive functions in patients with Alzheimer's disease. It is predominantly excreted unchanged via the kidneys, and patients with decreased creatinine clearance must be treated with lower doses of memantine. However, it is unclear whether memantine itself can lead to renal dysfunction and/or hyperkalaemia. We report a patient with renal impairment and hyperkalaemia possibly associated with memantine administration.

  16. [Cognitive plasticity in Alzheimer's disease patients receiving cognitive stimulation programs].

    PubMed

    Zamarrón Cassinello, Ma Dolores; Tárraga Mestre, Luis; Fernández-Ballesteros, Rocío

    2008-08-01

    The main purpose of this article is to examine whether cognitive plasticity increases after cognitive training in Alzheimer's disease patients. Twenty six patients participated in this study, all of them diagnosed with mild Alzheimer's disease, 17 of them received a cognitive training program during 6 months, and the other 9 were assigned to the control group. Participants were assigned to experimental or control conditions for clinical reasons. In order to assess cognitive plasticity, all patients were assessed before and after treatment with three subtests from the "Bateria de Evaluación de Potencial de Aprendizaje en Demencias" [Assessment Battery of Learning Potential in Dementia] (BEPAD). After treatment, Alzheimer's disease patients improved their performance in all the tasks assessing cognitive plasticity: viso-spatial memory, audio-verbal memory and verbal fluency. However, the cognitive plasticity scores of the patients in the control group decreased. In conclusion, this study showed that cognitive stimulation programs can improve cognitive functioning in mildly demented patients, and patients who do not receive any cognitive interventions may reduce their cognitive functioning.

  17. Positron emission tomography in patients with clinically diagnosed Alzheimer's disease.

    PubMed Central

    McGeer, P L; Kamo, H; Harrop, R; Li, D K; Tuokko, H; McGeer, E G; Adam, M J; Ammann, W; Beattie, B L; Calne, D B

    1986-01-01

    Fourteen patients who had clinically diagnosed Alzheimer's disease with mild to severe dementia (mean age 69.1 years) were evaluated by calculation of local cerebral metabolic rate for glucose (LCMR-gl) based on uptake of 18F-2-fluoro-2-deoxyglucose (FDG) detected with positron emission tomography (PET). PET scanning showed that the patients had significantly lower LCMR-gl values than 11 age-matched neurologically normal volunteers (mean age 66.3 years). The differences were most marked in the temporal cortex, followed by the frontal, parietal and occipital cortex. In each case the LCMR-gl value was below the lowest control value in at least one cortical area and usually in several; the reduction in LCMR-gl and the number of regions involved in the patients increased with the severity of the dementia. Deficits noted in neuropsychologic testing generally correlated with those predicted from loss of regional cortical metabolism. The patients with Alzheimer's disease were also examined with magnetic resonance imaging, computed tomography or both; the degree of atrophy found showed only a poor correlation with the neuropsychologic deficit. Significant atrophy was also noted in some of the controls. A detailed analysis of LCMR-gl values in selected cerebral regions of various sizes refuted the hypothesis that the reduction in cortical glucose metabolism in Alzheimer's disease is due to the filling by metabolically inert cerebrospinal fluid of space created by tissue atrophy. Images Fig. 2 Fig. 3 Fig. 4 Fig. 7 Fig. 8 Fig. 9 PMID:3512063

  18. Alzheimer's Disease

    MedlinePlus

    Alzheimer's disease (AD) is the most common form of dementia among older people. Dementia is a brain disorder that seriously affects a person's ability to carry out daily activities. AD begins slowly. It first involves the parts of ...

  19. Rapidly progressive Alzheimer disease.

    PubMed

    Schmidt, Christian; Wolff, Martin; Weitz, Michael; Bartlau, Thomas; Korth, Carsten; Zerr, Inga

    2011-09-01

    Different rates of progression have been observed among patients with Alzheimer disease. Risk factors that accelerate deterioration have been identified and some are being discussed, such as genetics, comorbidity, and the early appearance of Alzheimer disease motor signs. Progressive forms of Alzheimer disease have been reported with rapid cognitive decline and disease duration of only a few years. This short review aims to provide an overview of the current knowledge of rapidly progressive Alzheimer disease. Furthermore, we suggest that rapid, in this context, should be defined as a Mini-Mental State Examination score decrease of 6 points per year.

  20. Mitochondrial DNA sequence analysis of four Alzheimer`s and Parkinson`s disease patients

    SciTech Connect

    Brown, M.D.; Shoffner, J.M.; Wallace, D.C.

    1996-01-22

    The mitochondrial DNA (mtDNA) sequence was determined on 3 patients with Alzheimer`s disease (AD) exhibiting AD plus Parkinson`s disease (PD) neuropathologic changes and one patient with PD. Patient mtDNA sequences were compared to the standard Cambridge sequence to identify base changes. In the first AD + PD patient, 2 of the 15 nucleotide substitutions may contribute to the neuropathology, a nucleotide pair (np) 4336 transition in the tRNA{sup Gln} gene found 7.4 times more frequently in patients than in controls, and a unique np 721 transition in the 12S rRNA gene which was not found in 70 other patients or 905 controls. In the second AD + PD patient, 27 nucleotide substitutions were detected, including an np 3397 transition in the ND1 gene which converts a conserved methionine to a valine. In the third AD + PD patient, 2 polymorphic base substitutions frequently found at increased frequency in Leber`s hereditary optic neuropathy patients were observed, an np 4216 transition in ND1 and an np 13708 transition in the ND5 gene. For the PD patient, 2 novel variants were observed among 25 base substitutions, an np 1709 substitution in the 16S rRNA gene and an np 15851 missense mutation in the cytb gene. Further studies will be required to demonstrate a casual role for these base substitutions in neurodegenerative disease. 68 refs., 2 tabs.

  1. Memantine-induced Myoclonus in a Patient with Alzheimer Disease

    PubMed Central

    Murgai, Aditya A.; LeDoux, Mark S.

    2015-01-01

    Background Myoclonus can be a clinical manifestation of numerous neurodegenerative disorders and an adverse drug reaction to medications used in their treatment. Case Report Herein, we report memantine-induced myoclonus in a patient with Alzheimer disease. The myoclonus seen in our patient was generalized (proximal limbs and trunk), present at rest and with action, and stimulus sensitive. A structured evaluation with the Unified Myoclonus Rating Scale showed that the myoclonus had no significant effect on functional capacity. After discontinuation of memantine, myoclonus slowly resolved over the course of several weeks. Discussion Memantine may cause myoclonus in susceptible individuals. PMID:26317045

  2. Circulating plasmalogen levels and Alzheimer Disease Assessment Scale–Cognitive scores in Alzheimer patients

    PubMed Central

    Wood, Paul L.; Mankidy, Rishikesh; Ritchie, Shawn; Heath, Doug; Wood, Julie A.; Flax, John; Goodenowe, Dayan B.

    2010-01-01

    Background Plasmalogens, which are key structural phospholipids in brain membranes, are decreased in the brain and serum of patients with Alzheimer disease (AD). We performed this pilot study to evaluate the relation between the levels of circulating plasmalogens and Alzheimer Disease Assessment Scale–Cognitive (ADAS-Cog) scores in patients with AD. Methods We evaluated participants’ ADAS-Cog scores and serum plasmalogen levels. For the 40 included AD patients with an ADAS-Cog score between 20 and 46, we retested their ADAS-Cog score 1 year later. The levels of docosahexaenoic acid plasmalogen were measured by use of liquid chromatography–tandem mass spectrometry. Results We found that the ADAS-Cog score increased significantly in AD patients with circulating plasmalogen levels that were ≤ 75% of that of age-matched controls at entry into the study. There was no change in score among participants with normal serum plasmalogen levels at baseline (> 75%). Limitations This was a pilot study with 40 patients, and the results require validation in a larger population. Conclusion Our study demonstrates that decreased levels of plasmalogen precursors in the central nervous system correlate with functional decline (as measured by ADAS-Cog scores) in AD patients. The use of both ADAS-Cog and serum plasmalogen data may be a more accurate way of predicting cognitive decline in AD patients, and may be used to decrease the risk of including patients with no cognitive decline in the placebo arm of a drug trial. PMID:20040248

  3. Cognitive performance on Piagetian tasks by Alzheimer's disease patients.

    PubMed

    Thornbury, J M

    1992-02-01

    The purpose of this study was to examine cognitive abilities in Alzheimer's disease (AD) patients using Piaget's child developmental theory. Thirty elderly AD patients and 30 elderly control subjects were given two traditional Piagetian measures, the Infant Psychological Development Scale and the Concrete Operations Test. Half of the AD subjects (15) were in Piaget's sensorimotor or preoperational stages, while the remaining half of the AD subjects and all elderly control subjects were in Piaget's concrete operational stage, chi 2 [1, N = 60] = 17.42, p less than .001. If subsequent studies confirm that AD patients' cognitive characteristics are similar to Piaget's theoretical model, nursing care might be individualized based on mental competence, thus minimizing the commonly observed caregiver overestimation and underestimation of the AD patient's ability to understand and cooperate.

  4. Treatments for Alzheimer's Disease

    MedlinePlus

    ... 3900 Find your chapter: search by state Home > Alzheimer's Disease > Treatments Overview What Is Dementia? What Is Alzheimer's? ... and move closer to a cure. Treatments for Alzheimer's disease Currently, there is no cure for Alzheimer's. But ...

  5. Finger agnosia and cognitive deficits in patients with Alzheimer's disease.

    PubMed

    Davis, Andrew S; Trotter, Jeffrey S; Hertza, Jeremy; Bell, Christopher D; Dean, Raymond S

    2012-01-01

    The purpose of this study was to examine the presence of finger agnosia in patients with Alzheimer's disease (AD) and to determine if level of finger agnosia was related to cognitive impairment. Finger agnosia is a sensitive measure of cerebral impairment and is associated with neurofunctional areas implicated in AD. Using a standardized and norm-referenced approach, results indicated that patients with AD evidenced significantly decreased performance on tests of bilateral finger agnosia compared with healthy age-matched controls. Finger agnosia was predictive of cognitive dysfunction on four of seven domains, including: Crystallized Language, Fluid Processing, Associative Learning, and Processing Speed. Results suggest that measures of finger agnosia, a short and simple test, may be useful in the early detection of AD.

  6. Analysis of Retinal Peripapillary Segmentation in Early Alzheimer's Disease Patients

    PubMed Central

    Salobrar-Garcia, Elena; Hoyas, Irene; Leal, Mercedes; de Hoz, Rosa; Rojas, Blanca; Ramirez, Ana I.; Salazar, Juan J.; Yubero, Raquel; Gil, Pedro; Triviño, Alberto; Ramirez, José M.

    2015-01-01

    Decreased thickness of the retinal nerve fiber layer (RNFL) may reflect retinal neuronal-ganglion cell death. A decrease in the RNFL has been demonstrated in Alzheimer's disease (AD) in addition to aging by optical coherence tomography (OCT). Twenty-three mild-AD patients and 28 age-matched control subjects with mean Mini-Mental State Examination 23.3 and 28.2, respectively, with no ocular disease or systemic disorders affecting vision, were considered for study. OCT peripapillary and macular segmentation thickness were examined in the right eye of each patient. Compared to controls, eyes of patients with mild-AD patients showed no statistical difference in peripapillary RNFL thickness (P > 0.05); however, sectors 2, 3, 4, 8, 9, and 11 of the papilla showed thinning, while in sectors 1, 5, 6, 7, and 10 there was thickening. Total macular volume and RNFL thickness of the fovea in all four inner quadrants and in the outer temporal quadrants proved to be significantly decreased (P < 0.01). Despite the fact that peripapillary RNFL thickness did not statistically differ in comparison to control eyes, the increase in peripapillary thickness in our mild-AD patients could correspond to an early neurodegeneration stage and may entail the existence of an inflammatory process that could lead to progressive peripapillary fiber damage. PMID:26557684

  7. [Alzheimer and the discovery of Alzheimer's disease].

    PubMed

    Zhagn, Lili; Li, Zhiping

    2014-09-01

    Alzheimer was born in Germany in 1864. In 1887, Alzheimer graduated with a medical doctor degree at the University of Würzburg. In 1888, Alzheimer began to work in the Community Hospital for Mental and Epileptic Patients in Frankfurt am Main for 14 years. During this time, Alzheimer published the six-volume Histologic and Histopathologic Studies of the Cerebral Cortex, with co-author Franz Nissl. In 1903, Alzheimer came to work in the Royal Psychiatric Clinic of the University of Munich. One year later, he published his postdoctoral paper of Histological Studies about the Differential Diagnosis of Progressive Paralysis in 1904. In 1912, Alzheimer was provided the chair of psychiatry at the University of Breslau. On the way to Breslau, Alzheimer got sick, and eventually died in 1915. In 1906, Alzheimer found numerous amyloid plaques and neurofibrillary tangles in the brain of a patient called Auguste under the microscope. In November of the same year, Alzheimer gave a lecture about Auguste's case at the 37(th) Conference of South-West German Psychiatrists in Tübingen, which received little attention. In 1910, Kraepelin mentioned "Alzheimer's disease" for the first time to name the disease of what Auguste got in the 8th edition of Handbook of Psychiatry. Therefore, Alzheimer achieved worldwide recognition.

  8. The minute hand phenomenon in the Clock Test of patients with early Alzheimer disease.

    PubMed

    Leyhe, Thomas; Milian, Monika; Müller, Stephan; Eschweiler, Gerhard W; Saur, Ralf

    2009-06-01

    Common scoring systems for the Clock Test do not sufficiently emphasize the correct time representation by the clock hands. We compared Clock Drawing, Clock Setting, and Clock Reading in healthy control persons, patients with mild cognitive impairment, early Alzheimer disease and progressed Alzheimer disease particularly analyzing clock time representation. We found that healthy control persons and participants with mild cognitive impairment did not show any impairment in Clock Test performance. Patients with early Alzheimer disease could be discriminated from healthy control persons and participants with mild cognitive impairment solely by misplacement of the minute hand in Clock Drawing and Clock Setting. The progressed Alzheimer disease group showed significantly more impairments in all Clock Test variants. It is assumed that early stage Alzheimer disease patient deficits in Clock Tests are mainly determined by a reduced access to semantic memory about the appearance and functionality of a clock.

  9. CSF tau levels influence cortical plasticity in Alzheimer's disease patients.

    PubMed

    Koch, Giacomo; Esposito, Zaira; Kusayanagi, Hajime; Monteleone, Fabrizia; Codecá, Claudia; Di Lorenzo, Francesco; Caltagirone, Carlo; Bernardi, Giorgio; Martorana, Alessandro

    2011-01-01

    Alzheimer's disease (AD) is a neurodegenerative process characterized by progressive neuronal degeneration, reduced levels of neurotransmitters, and altered forms of synaptic plasticity. In animal models of AD, amyloid-β (Aβ) and tau proteins are supposed to interfere with synaptic transmission. In the current study, we investigated the correlation between motor cortical plasticity, measured with 1 Hz repetitive transcranial magnetic stimulation (rTMS), and the levels of Aβ₁₋₄₂, total tau (t-Tau), and phosphorylated tau (p-Tau) detected in cerebrospinal fluid (CSF) of AD patients. We found that the overall rTMS after effects were milder in AD patients in comparison with controls. In AD patients the amount of rTMS-induced inhibition correlated with CSF t-Tau, but not with Aβ₁₋₄₂ CSF levels. Surprisingly, higher CSF t-Tau levels were associated to a stronger inhibition of the motor evoked potentials, implying that the expected effects of the 1 Hz rTMS protocol were more evident in patients with more pathological t-Tau CSF levels. These data could be interpreted as the consequence of CSF t-Tau mediated abnormal excitatory activity and could suggest that CSF t-Tau may impact mechanisms of cortical plasticity.

  10. Neuropathology of parkinsonism in patients with pure Alzheimer's disease.

    PubMed

    Horvath, Judit; Burkhard, Pierre R; Herrmann, François R; Bouras, Constantin; Kövari, Enikö

    2014-01-01

    About one third of Alzheimer's disease (AD) patients develop some parkinsonian features, yet half of them do not have Lewy body pathology at autopsy. The neuropathological substrate of parkinsonism in AD is still unclear. In the present study, we measured neuronal and neurofibrillary tangles (NFTs) densities in the substantia nigra pars compacta (SN) and in the putamen of 22 AD patients, 11 with and 11 without parkinsonism, here defined as the presence of bradykinesia and at least one of resting tremor, rigidity, or gait disorders. Our study showed that parkinsonism associated with AD was related to a significant loss of neurons both in the SN and in the putamen, suggesting pre-and postsynaptic alterations of the nigrostriatal pathway. Neuronal tau deposition was a less important factor as density of NFTs correlated with parkinsonism only in the SN but not in the putamen. We propose that a subgroup of pure AD patients develop parkinsonian symptoms as a result of neuronal loss in the basal ganglia, indicating a prominent subcortical involvement, which appears unrelated to the Braak stage of AD.

  11. Family History of Alzheimer's Disease and Cortical Thickness in Patients With Dementia.

    PubMed

    Ganske, Steffi; Haussmann, Robert; Gruschwitz, Antonia; Werner, Annett; Osterrath, Antje; Baumgaertel, Johanna; Lange, Jan; Donix, Katharina L; Linn, Jennifer; Donix, Markus

    2016-08-01

    A first-degree family history of Alzheimer's disease reflects genetic risks for the neurodegenerative disorder. Recent imaging data suggest localized effects of genetic risks on brain structure in healthy people. It is unknown whether this association can also be found in patients who already have dementia. Our aim was to investigate whether family history risk modulates regional medial temporal lobe cortical thickness in patients with Alzheimer's disease. We performed high-resolution magnetic resonance imaging and cortical unfolding data analysis on 54 patients and 53 nondemented individuals. A first-degree family history of Alzheimer's disease was associated with left hemispheric cortical thinning in the subiculum among patients and controls. The contribution of Alzheimer's disease family history to regional brain anatomy changes independent of cognitive impairment may reflect genetic risks that modulate onset and clinical course of the disease.

  12. Music as a memory enhancer in patients with Alzheimer's disease.

    PubMed

    Simmons-Stern, Nicholas R; Budson, Andrew E; Ally, Brandon A

    2010-08-01

    Musical mnemonics have a long and diverse history of popular use. In addition, music processing in general is often considered spared by the neurodegenerative effects of Alzheimer's disease (AD). Research examining these two phenomena is limited, and no work to our knowledge has explored the effectiveness of musical mnemonics in AD. The present study sought to investigate the effect of music at encoding on the subsequent recognition of associated verbal information. Lyrics of unfamiliar children's songs were presented bimodally at encoding, and visual stimuli were accompanied by either a sung or a spoken recording. Patients with AD demonstrated better recognition accuracy for the sung lyrics than the spoken lyrics, while healthy older adults showed no significant difference between the two conditions. We propose two possible explanations for these findings: first, that the brain areas subserving music processing may be preferentially spared by AD, allowing a more holistic encoding that facilitates recognition, and second, that music heightens arousal in patients with AD, allowing better attention and improved memory.

  13. From here to epilepsy: the risk of seizure in patients with Alzheimer's disease.

    PubMed

    Nicastro, Nicolas; Assal, Frédéric; Seeck, Margitta

    2016-03-01

    To describe the association between Alzheimer's disease and seizures by reviewing epidemiological data from available literature and to assess the putative pathophysiological links between neurodegeneration and altered cortical excitability. We also discuss specific antiepileptic treatment strategies in patients with Alzheimer's disease, as well as transient epileptic amnesia as a possible crossroads between degeneration and epilepsy. Regarding epidemiology, we searched publications in Pubmed, Medline, Scopus and Web of Science (until September 2015) using the keywords "incidence", "prevalence" and "frequency", as well as "Alzheimer's disease" and "seizures". In addition, therapeutic aspects for seizures in Alzheimer's disease were searched using the key words "antiepileptic drugs", "seizure treatment" and "Alzheimer". The prevalence and incidence rates of seizures were found to be increased 2 to 6-fold in patients with Alzheimer's disease compared to age-adjusted control patients. Treatment strategies have mainly been extrapolated from elderly patients without dementia, except for one single randomised trial, in which levetiracetam, lamotrigine and phenobarbital efficacy and tolerance were investigated in patients with Alzheimer's disease. Mouse models appear to show a major role of amyloid precursor protein and its cleavage products in the generation of cortical hyperexcitability. A link between Alzheimer's disease and epilepsy has long been described and recent cohort studies have more clearly delineated risk factors associated with the genesis of seizures, such as early onset and possibly severity of dementia. As genetic forms of Alzheimer's disease and experimental mouse models suggest, beta-amyloid may play a prominent role in the propagation of synchronised abnormal discharges, perhaps more via an excitatory mode than a direct neurodegenerative effect.

  14. Naming ability in patients with mild to moderate Alzheimer's disease: what changes occur with the evolution of the disease?

    PubMed Central

    Silagi, Marcela Lima; Bertolucci, Paulo Henrique Ferreira; Ortiz, Karin Zazo

    2015-01-01

    OBJECTIVES: Naming deficit is a linguistic symptom that appears in the initial phase of Alzheimer's disease, but the types of naming errors and the ways in which this deficit changes over the course of the disease are unclear. We analyzed the performance of patients with Alzheimer's disease on naming tasks during the mild and moderate phases and verified how this linguistic skill deteriorates over the course of the disease. METHODS: A reduced version of the Boston Naming Test was administered to 30 patients with mild Alzheimer's disease, 30 patients with moderate Alzheimer's disease and 30 healthy controls. Errors were classified as verbal semantic paraphasia, verbal phonemic paraphasia, no response (pure anomia), circumlocution, unrelated verbal paraphasia, visual errors or intrusion errors. RESULTS: The patients with moderate Alzheimer's disease had significantly fewer correct answers than did both the control group and the group with mild Alzheimer's disease. With regard to the pattern of errors, verbal semantic paraphasia errors were the most frequent errors in all three groups. Additionally, as the disease severity increased, there was an increase in the number of no-response errors (pure anomia). The group with moderate Alzheimer's disease demonstrated a greater incidence of visual errors and unrelated verbal paraphasias compared with the other two groups and presented a more variable pattern of errors. CONCLUSIONS: Performance on nominative tasks worsened as the disease progressed in terms of both the quantity and the type of errors encountered. This result reflects impairment at different levels of linguistic processing. PMID:26106961

  15. Treatment of Alzheimer disease.

    PubMed

    Winslow, Bradford T; Onysko, Mary K; Stob, Christian M; Hazlewood, Kathleen A

    2011-06-15

    Alzheimer disease is the most common form of dementia, affecting nearly one-half [corrected] of Americans older than 85 years. It is characterized by progressive memory loss and cognitive decline. Amyloid plaque accumulation, neurofibrillary tau tangles, and depletion of acetylcholine are among the pathologic manifestations of Alzheimer disease. Although there are no proven modalities for preventing Alzheimer disease, hypertension treatment, omega-3 fatty acid supplementation, physical activity, and cognitive engagement demonstrate modest potential. Acetylcholinesterase inhibitors are first-line medications for the treatment of Alzheimer disease, and are associated with mild improvements in cognitive function, behavior, and activities of daily living; however, the clinical relevance of these effects is unclear. The most common adverse effects of acetylcholinesterase inhibitors are nausea, vomiting, diarrhea, dizziness, confusion, and cardiac arrhythmias. Short-term use of the N-methyl-D-aspartate receptor antagonist memantine can modestly improve measures of cognition, behavior, and activities of daily living in patients with moderate to severe Alzheimer disease. Memantine can also be used in combination with acetylcholinesterase inhibitors. Memantine is generally well tolerated, but whether its benefits produce clinically meaningful improvement is controversial. Although N-methyl-D-aspartate receptor antagonists and acetylcholinesterase inhibitors can slow the progression of Alzheimer disease, no pharmacologic agents can reverse the progression. Atypical antipsychotics can improve some behavioral symptoms, but have been associated with increased mortality rates in older patients with dementia. There is conflicting evidence about the benefit of selegiline, testosterone, and ginkgo for the treatment of Alzheimer disease. There is no evidence supporting the beneficial effects of vitamin E, estrogen, or nonsteroidal anti-inflammatory drug therapy.

  16. Alzheimer's Disease and Depression.

    ERIC Educational Resources Information Center

    Teri, Linda; Wagner, Amy

    1992-01-01

    Reviews research on depression in Alzheimer's disease (AD). Discusses evidence suggesting that depression affects many AD patients and can have profound effects on patient long-term functioning and caregiver well-being. Notes that field is dominated by studies of prevalence, as opposed to studies of etiology, association with other aspects of…

  17. Efficacy of music therapy in treatment for the patients with Alzheimer's disease.

    PubMed

    Fukui, H; Arai, A; Toyoshima, K

    2012-01-01

    We report that music therapy is effective in the treatment of Alzheimer's disease. We found that the secretion of 17β-estradiol and testosterone, hormones that are supposed to have preventive effects on Alzheimer's disease, is significantly increased by music therapy. During the sessions, patients with Alzheimer's disease were allowed to listen to music and songs with verbal contact from the therapist. It was found that problematic behaviors such as poriomania (fugue) had decreased. Music therapy has the potential as an alternative treatment for adverse hormone replacement therapy.

  18. Perception of Fechner Illusory Colors in Alzheimer Disease Patients

    PubMed Central

    Kaubrys, Gintaras; Bukina, Vera; Bingelytė, Ieva; Taluntis, Vladas

    2016-01-01

    Background Alzheimer disease (AD) primarily affects cognition. A variety of visual disorders was established in AD. Fechner illusory colors are produced by a rotating disk with a black and white pattern. The purpose of our research was to explore the perception of illusory colors in AD. Material/Methods W recruited 40 AD patients (MMSE ≥14) and 40 normal controls (CG group) matched by age, education, gender in this prospective, cross-sectional, case-control study. An achromatic Benham’s disk attached to a device to control the speed and direction of rotation was used to produce illusory colors. Primary, secondary, and tertiary RGB system colors were used for matching of illusory and physical colors. Results Subjects in the AD group perceived less illusory colors in 5 arcs (p<0.05) of the 8 arcs assessed. The biggest difference was found between AD and CG groups for pure blue (χ2=26.87, p<0.001 clockwise, χ2=22.75, p<0.001 counter-clockwise). Groups did not differ in perception of pure yellow opponent colors (p>0.05). Mixed colors of the blue-yellow axis were perceived less often in AD, but more frequently than pure blue (#0000FF). The sequence of colors on Benham’s disk followed a complex pattern, different from the order of physical spectral colors and opponent processes-based colors. Conclusions AD patients retained reduced perception of illusory colors. The perception of pure blue illusory color is almost absent in AD. The asymmetrical shift to the yellow opponent is observed in AD with red prevailing over green constituent. This may indicate cortical rather than retinal impairment. PMID:27902677

  19. Cerebrolysin in Alzheimer's disease.

    PubMed

    Antón Álvarez, X; Fuentes, Patricio

    2011-07-01

    Cerebrolysin is a neuropeptide preparation mimicking the action of endogenous neurotrophic factors. Positive effects of Cerebrolysin on β-amyloid- and tau-related pathologies, neuroinflammation, neurotrophic factors, oxidative stress, excitotoxicity, neurotransmission, brain metabolism, neuroplasticity, neuronal apoptosis and degeneration, neurogenesis and cognition were demonstrated in experimental conditions. These pleiotropic effects of Cerebrolysin on Alzheimer's disease-related pathogenic events are consistent with a neurotrophic-like mode of action, and seems to involve the activation of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase-3 β intracellular signaling pathway. The clinical efficacy of Cerebrolysin in Alzheimer's disease was evaluated in several randomized, double-blind, clinical trials, showing consistent benefits on global clinical function and cognition, improvements in behavior at high doses, and minor effects on daily living activities in patients with mild to moderate Alzheimer's disease, as well as in subgroups of moderate to moderately severe patients. In addition, the clinical benefits of Cerebrolysin were largely maintained for several months after ending treatment, a finding that supports its discontinuous administration. Cerebrolysin was generally well tolerated and did not induce significant adverse events in Alzheimer's patients. Although long-term studies are needed, the data available suggest that Cerebrolysin is effective as monotherapy and constitutes a promising option for combined therapy in Alzheimer's disease.

  20. Seizures in an Alzheimer's disease patient as a complication of colonoscopy premedication with meperidine.

    PubMed

    Nagler, Jerry; Hammarth, Patricia M; Poppers, David M

    2008-01-01

    We describe the first reported case of generalized tonic-clonic seizures induced by meperidine premedication for a colonoscopy procedure in a 63-year-old woman with Alzheimer's disease. The active metabolite of meperidine, normeperidine, is postulated to be the precipitating cause of the seizures, although a cholinesterase inhibitor and an N-methyl-D: -aspartate receptor antagonist, both routinely used for treatment of Alzheimer's disease, may have contributed by reducing the seizure threshold. The neuronal changes which occur in Alzheimer's disease can themselves also predispose to seizures. We recommend avoidance of meperidine for all flexible endoscopic procedures on patients with Alzheimer's disease and in any patient with a condition that predisposes to seizures, and suggest the use of alternative opioids.

  1. [Biomarkers of Alzheimer disease].

    PubMed

    Rachel, Wojciech; Grela, Agatha; Zyss, Tomasz; Zieba, Andrzej; Piekoszewski, Wojciech

    2014-01-01

    Cognitive impairment is one of the most abundant age-related psychiatric disorders. The outcome of cognitive impairment in Alzheimer's disease has both individual (the patients and their families) and socio-economic effects. The prevalence of Alzheimer's disease doubles after the age of 65 years, every 4.5 years. An etiologically heterogenic group of disorders related to aging as well as genetic and environmental interactions probably underlie the impairment in Alzheimer's disease. Those factors cause the degeneration of brain tissue which leads to significant cognitive dysfunction. There are two main hypotheses that are linked to the process of neurodegeneration: (i) amyloid cascade and (ii) the role of secretases and dysfunction of mitochondria. From the therapeutic standpoint it is crucial to get an early diagnosis and start with an adequate treatment. The undeniable progress in the field of biomarker research should lead to a better understanding of the early stages of the disorder. So far, the best recognised and described biomarkers of Alzheimer's disease, which can be detected in both cerebrospinal fluid and blood, are: beta-amyloid, tau-protein and phosphorylated tau-protein (phospho-tau). The article discusses the usefulness of the known biomarkers of Alzheimer's disease in early diagnosis.

  2. The Missing Link between Faces and Names: Evidence from Alzheimer's Disease Patients

    ERIC Educational Resources Information Center

    Calabria, Marco; Sabio, Alicia; Martin, Clara; Hernandez, Mireia; Juncadella, Montserrat; Gascon-Bayarri, Jordi; Rene, Ramon; Ortiz-Gil, Jordi; Ugas, Lidia; Costa, Albert

    2012-01-01

    Retrieval of proper names is a cause of concern and complaint among elderly adults and it is an early symptom of patients suffering from neurodegenerative diseases such as Alzheimer's disease (AD). While it is well established that AD patients have deficits of proper name retrieval, the nature of such impairment is not yet fully understood.…

  3. The Short-Term Effects of In-Hospital Respite on the Patient with Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Seltzer, Benjamin; And Others

    1988-01-01

    Assessed cognitive and functional status levels of Alzheimer's disease patients prior to admission to two-week in-hospital respite program and at conclusion of respite. Found that patients with poorest status tended to show improvement on some measures following respite. Patients with higher initial levels of performance tended to show slight…

  4. Inflammatory signaling in Alzheimer disease and depression.

    PubMed

    Barber, Robert

    2011-08-01

    To help define the relationships among inflammation, Alzheimer disease, and depression, the Texas Alzheimer's Research Consortium analyzed an array of inflammatory biomarkers in a cohort of patients with Alzheimer disease and in controls. Inflammation severity was highly correlated with earlier age at onset of Alzheimer disease and was also associated with cognitive decline. The relationship between inflammation and depression was not as clear, and it varied with aspects of depression, gender, and the presence of Alzheimer disease.

  5. Alzheimer's Disease: The Death of the Disease.

    ERIC Educational Resources Information Center

    McBroom, Lynn W.

    1987-01-01

    Alzheimer's disease, a form of dementia in middle-age and older adults is becoming more evident because of growing numbers of older people and better diagnosis and detection methods. Describes the behavioral and physical symptoms of the disease as well as specific suggestions for care of patients with Alzheimer's disease, including dealing with…

  6. Mitochondrial DNA variants observed in Alzheimer disease and Parkinson disease patients

    SciTech Connect

    Shoffner, J.M.; Brown, M.D.; Torroni, A.; Lott, M.T.; Cabell, M.F.; Mirra, S.S.; Yang, C.C.; Gearing, M.; Salvo, R. ); Beal, M.F. )

    1993-07-01

    Mitochondrial DNA (mtDNA) variants associated with Alzheimer disease (AD) and Parkinson disease (PD) were sought by restriction endonuclease analysis in a cohort of 71 late-onset Caucasian patients. A tRNA[sup Gln] gene variant at nucleotide pair (np) 4336 that altered a moderately conserved nucleotide was present in 9/173 (5.2%) of the patients surveyed but in only 0.7% of the general Caucasian controls. One of these patients harbored an additional novel 12S rRNA 5-nucleotide insertion at np 956-965, while a second had a missense variant at np 3397 that converted a highly conserved methionine to a valine. This latter mutation was also found in an independent AD + PD patient, as was a heteroplasmic 16S rRNA variant at np 3196. Additional studies will be required to determine the significance, if any, of these mutations. 122 refs., 4 figs., 2 tabs.

  7. An Intervention That Delays Institutionalization of Alzheimer's Disease Patients: Treatment of Spouse-Caregivers.

    ERIC Educational Resources Information Center

    Mittelman, Mary S.; And Others

    1993-01-01

    Randomly assigned spouse-caregivers of Alzheimer's disease patients to treatment group (individual and family counseling, support group participation, and ad hoc consultation) or control group (only routine support). Treatment group had less than half as many nursing home placements as control group. Placement also was affected by patient's need…

  8. Comprehension of metaphors and idioms in patients with Alzheimer's disease: a longitudinal study.

    PubMed

    Papagno, C

    2001-07-01

    Language in patients with Alzheimer's disease has been extensively studied, with the exception of non-literal language comprehension. However, in our speech, we often make use of expressions, which are not necessarily interpreted on a literal ground. Comprehension of metaphors and idioms was examined in 39 patients with probable early Alzheimer's disease. The results showed that the decline of figurative language is not an early symptom of dementia and can occur independently from the impairment of propositional language. It was also found that metaphors and idioms differ as far as the predominant kind of error is concerned.

  9. Presentation and stability of noncognitive symptom patterns in patients with Alzheimer disease.

    PubMed

    Haupt, M; Jänner, M; Ebeling, S; Stierstorfer, A; Kretschmar, C

    1998-12-01

    The purpose of this study was to investigate noncognitive symptoms in Alzheimer disease to identify symptom patterns and to study stability of such patterns prospectively. Furthermore, variables were examined that could be associated with certain types of symptom patterns or could be predictors of change of these patterns. Forty-eight patients with the clinical diagnosis of probable Alzheimer disease were included in this study and were assessed weekly over a 3-week period. Noncognitive symptoms were rated according to the Behavioral Abnormalities in Alzheimer's Disease Rating Scale and the Dementia Mood Assessment Scale and to a set of items that specifically assess misidentifications. By means of principal component factor analysis different noncognitive symptom patterns were obtained, yielding a four-factor solution. They mapped onto rational domains with respect to clinical experience: depression, apathy, psychotic symptoms/aggression, and misidentifications/agitation. Demographic and clinical variables were not associated with the factor solutions and did not predict change of the factor values. The results demonstrate that in Alzheimer disease there are distinct noncognitive symptom patterns that hold at least short-term prospective stability. None of the examined clinical variables, such as age at entry, the status of the patients (outpatient or inpatient), or dementia severity, exerted substantial influence on the noncognitive symptom patterns. Further investigations should concentrate on the pathological and prognostic correlates of noncognitive symptom patterns in Alzheimer disease.

  10. Do Alzheimer's Disease Patients Want to Participate in a Treatment Decision, and Would Their Caregivers Let Them?

    ERIC Educational Resources Information Center

    Hirschman, Karen B.; Joyce, Colette M.; James, Bryan D.; Xie, Sharon X.; Karlawish, Jason H.T.

    2005-01-01

    Purpose: This study was designed to examine the factors associated with the preferences of Alzheimer's disease patients to participate in a decision to use an Alzheimer's disease-slowing medication and how involved their caregivers would let them be in this decision. Design and Methods: Interviews were conducted with 48 patients in the…

  11. Genetics of Alzheimer's Disease

    PubMed Central

    Ridge, Perry G.; Ebbert, Mark T. W.; Kauwe, John S. K.

    2013-01-01

    Alzheimer's disease is the most common form of dementia and is the only top 10 cause of death in the United States that lacks disease-altering treatments. It is a complex disorder with environmental and genetic components. There are two major types of Alzheimer's disease, early onset and the more common late onset. The genetics of early-onset Alzheimer's disease are largely understood with variants in three different genes leading to disease. In contrast, while several common alleles associated with late-onset Alzheimer's disease, including APOE, have been identified using association studies, the genetics of late-onset Alzheimer's disease are not fully understood. Here we review the known genetics of early- and late-onset Alzheimer's disease. PMID:23984328

  12. [Driving and Alzheimer's disease].

    PubMed

    Roche, Jean

    2005-09-01

    Although most aged people remain safe drivers, a greater risk for crashes due to medical conditions is observed in the elderly. Impairment of important functions for safe driving such as visuospatial skills, attention, memory and judgement are observed in dementia, particularly in Alzheimer's disease. The accident rate increases from 9.4 accidents per million vehicle kilometers traveled for 80 to 85 year-old drivers, but raises to 163.6 for drivers with moderate AD. Patients and their families should be informed that patients with mild dementia related to Alzheimer's disease (stage 1 on the Clinical Dementia Rating, CDR), have a substantially increased rate of traffic accidents and therefore should not drive. But subjects in the pre-dementia phase (stage 0.5 at the CDR, mild cognitive impairment) also pose significant driving safety problems. In most States of the USA, and many European countries, but not in France, law requires regular investigating of driving performance in the elderly.

  13. Walking difficulties in patients with Alzheimer's disease might originate from gait apraxia

    PubMed Central

    Della, S; Spinnler, H; Venneri, A

    2004-01-01

    Objectives: To investigate whether gait apraxia is a possible cause for some of the walking abnormalities shown by patients with Alzheimer's disease. Methods: 60 patients with Alzheimer's disease, selected as being free from overt extrapyramidal impairment or other potential causes of walking deficits, were assessed with a new test evaluating aspects of walking and related movements. Norms for this test were collected from a sample of 182 healthy volunteers. Results: 40% of the Alzheimer group performed below the cut off score on this test, and half performed poorly. Performance of the Alzheimer group in the walking skills test correlated highly with scores in a test assessing limb apraxia and with dementia severity. Conclusions: Gait apraxia may be the cause of walking disorders found in a subgroup of patients with Alzheimer's disease. Its detection is made easier by the use of a standardised test, but still relies heavily on the exclusion of other causes of walking deficits. It is a recognisable and independent form of apraxia. PMID:14742586

  14. Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease

    SciTech Connect

    van Duinen, S.G.; Castano, E.M.; Prelli, F.; Bots, G.T.A.B.; Luyendijk, W.; Frangione, B.

    1987-08-01

    Hereditary cerebral hemorrhage with amyloidosis in Dutch patients is an autosomal dominant form of vascular amyloidosis restricted to the leptomeninges and cerebral cortex. Clinically the disease is characterized by cerebral hemorrhages leading to an early death. Immunohistochemical studies of five patients revealed that the vascular amyloid deposits reacted intensely with an antiserum raised against a synthetic peptide homologous to the Alzheimer disease-related ..beta..-protein. Silver stain-positive, senile plaque-like structures were also labeled by the antiserum, yet these lesions lacked the dense amyloid cores present in typical plaques of Alzheimer disease. No neurofibrillary tangles were present. Amyloid fibrils were purified from the leptomeningeal vessels of one patient who clinically had no signs of dementia. The protein had a molecular weight of approx. 4000 and its partial amino acid sequence to position 21 showed homology to the ..beta..-protein of Alzheimer disease and Down syndrome. These results suggest that hereditary cerebral hemorrhage with amyloidosis of Dutch origin is pathogenetically related to Alzheimer disease and support the concept that the initial amyloid deposition in this disorder occurs in the vessel walls before damaging the brain parenchyma. Thus, deposition of ..beta..-protein in brain tissue seems to be related to a spectrum of diseases involving vascular syndromes, progressive dementia, or both.

  15. [Approach of the sexuality of Alzheimer's disease patients according to caregivers' guides approach].

    PubMed

    Ostrowski, Madeleine; Mietkiewicz, Marie-Claude

    2015-12-01

    If sexual behavior disorders are not a major symptom of Alzheimer's disease, they might be a source for suffering and hardship to the patient's entourage, especially since it is usually not easy to address sexuality. Guides for relatives have been devoted to improve their knowledge about the disease and to help providing best care for the patient. Thirty of the forty-six guides make references to sexual behavior disorders in Alzheimer's disease patients, sometimes in a few lines, sometimes in a few paragraphs illustrated by clinical vignettes. All these guides report two types of sexual disorders, loss of interest and decreased sexual activity, or inappropriate sexual behavior, and give advices to help relatives, spouses and children, managing the patient's sexual disorders without blaming the patients.

  16. Simple method for evaluation of planum temporale pyramidal neurons shrinkage in postmortem tissue of Alzheimer disease patients.

    PubMed

    Kutová, Martina; Mrzílková, Jana; Kirdajová, Denisa; Řípová, Daniela; Zach, Petr

    2014-01-01

    We measured the length of the pyramidal neurons in the cortical layer III in four subregions of the planum temporale (transitions into superior temporal gyrus, Heschl's gyrus, insular cortex, and Sylvian fissure) in control group and Alzheimer disease patients. Our hypothesis was that overall length of the pyramidal neurons would be smaller in the Alzheimer disease group compared to controls and also there would be right-left asymmetry in both the control and Alzheimer disease groups. We found pyramidal neuron length asymmetry only in controls--in the transition into the Sylvian fissure--and the rest of the subregions in the control group and Alzheimer disease patients did not show size difference. However, control-Alzheimer disease group pyramidal neuron length comparison revealed (a) no length difference in superior temporal gyrus transition area, (b) reversal of asymmetry in the insular transition area with left insular transition significantly shorter in the Alzheimer disease group compared to the control group, (c) both right and left Heschl's gyrus transitions significantly shorter in the Alzheimer disease group compared to the control group, and (d) right Sylvian fissure transition significantly shorter in the Alzheimer disease group compared to the control group. This neuronal length measurement method could supplement already existing neuropathological criteria for postmortem Alzheimer disease diagnostics.

  17. Effects of a multidisciplinar cognitive rehabilitation program for patients with mild Alzheimer's disease

    PubMed Central

    Viola, Luciane F.; Nunes, Paula V.; Yassuda, Monica S.; Aprahamian, Ivan; Santos, Franklin S.; Santos, Glenda D.; Brum, Paula S.; Borges, Sheila M.; Oliveira, Alexandra M.; Chaves, Gisele F. S.; Ciasca, Eliane C.; Ferreira, Rita C. R.; de Paula, Vanessa J. R.; Takeda, Oswaldo H.; Mirandez, Roberta M.; Watari, Ricky; Falcão, Deusivania V. S.; Cachioni, Meire; Forlenza, Orestes V.

    2011-01-01

    OBJECTIVE: To evaluate the effects of a multidisciplinary rehabilitation program on cognition, quality of life, and neuropsychiatric symptoms in patients with mild Alzheimer's disease. METHOD: The present study was a single-blind, controlled study that was conducted at a university-based day-hospital memory facility. The study included 25 Alzheimer's patients and their caregivers and involved a 12-week stimulation and psychoeducational program. The comparison group consisted of 16 Alzheimer's patients in waiting lists for future intervention. INTERVENTION: Group sessions were provided by a multiprofessional team and included memory training, computer-assisted cognitive stimulation, expressive activities (painting, verbal expression, writing), physiotherapy, and physical training. Treatment was administered twice a week during 6.5-h gatherings. MEASUREMENTS: The assessment battery comprised the following tests: Mini-Mental State Examination, Short Cognitive Test, Quality of Life in Alzheimer's disease, Neuropsychiatric Inventory, and Geriatric Depression Scale. Test scores were evaluated at baseline and the end of the study by raters who were blinded to the group assignments. RESULTS: Measurements of global cognitive function and performance on attention tasks indicated that patients in the experimental group remained stable, whereas controls displayed mild but significant worsening. The intervention was associated with reduced depression symptoms for patients and caregivers and decreased neuropsychiatric symptoms in Alzheimer's subjects. The treatment was also beneficial for the patients' quality of life. CONCLUSION: This multimodal rehabilitation program was associated with cognitive stability and significant improvements in the quality of life for Alzheimer's patients. We also observed a significant decrease in depressive symptoms and caregiver burden. These results support the notion that structured nonpharmacological interventions can yield adjunct and

  18. The Influences of Physical Activity on Patterns of Sleep Behavior of Patients with Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Namazi, Kevan H.; And Others

    1995-01-01

    A light exercise program was set up for 11 patients with Alzheimer's disease who exercised each day for 40 minutes. Their sleep patterns were compared with a control group who did not exercise. Results indicate that those who participated in the exercise program manifested 40% less restless behavior, while those in the non-exercise group showed a…

  19. The Effects of Alzheimer's Disease on Close Relationships between Patients and Caregivers.

    ERIC Educational Resources Information Center

    Blieszner, Rosemary; Shifflett, Peggy A.

    1990-01-01

    Interviewed 11 caregivers for early-stage Alzheimer's patients to investigate changes in relationships concurrently with onset and progress of disease. Over 18 months, intimacy declined in both spouse and parent-child relationships. Caregivers were saddened at loss of reciprocal aspects of relationship and had difficulty coping with uncertain…

  20. The Use of Errorless Learning Strategies for Patients with Alzheimer's Disease: A Literature Review

    ERIC Educational Resources Information Center

    Li, Ruijie; Liu, Karen P. Y.

    2012-01-01

    The aim of this article was to review the evidence of errorless learning on learning outcomes in patients with early-stage Alzheimer's disease. A computer-aided literature search from 1999 to 2011 was carried out using MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and PsycArticles. Keywords included…

  1. Coping & Caring: Living with Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Leroux, Charles

    This guide on Alzheimer's disease is for those who care for Alzheimer's patients, as well as those who want to learn more about the disease. It answers these questions: (1) what is Alzheimer's? (2) how does the disease progress and how long does it last? (3) how do families cope? and (4) who can provide assistance and information? The guide also…

  2. [Music therapy and Alzheimer disease].

    PubMed

    Tromeur, Emilie

    2014-01-01

    Music therapy and Alzheimer's dementia. Dementia such as Alzheimer's leads to the deterioration of the patient's global capacities. The cognitive disorders associated with it are disabling and affect every area of the patient's life. Every therapy's session undertaken with and by patients can act as a mirror of the progress of their disease and help to feel better, as described in this article on music therapy.

  3. Alzheimer's disease and memory-monitoring impairment: Alzheimer's patients show a monitoring deficit that is greater than their accuracy deficit.

    PubMed

    Dodson, Chad S; Spaniol, Maggie; O'Connor, Maureen K; Deason, Rebecca G; Ally, Brandon A; Budson, Andrew E

    2011-07-01

    We assessed the ability of two groups of patients with mild Alzheimer's disease (AD) and two groups of older adults to monitor the likely accuracy of recognition judgments and source identification judgments about who spoke something earlier. Alzheimer's patients showed worse performance on both memory judgments and were less able to monitor with confidence ratings the likely accuracy of both kinds of memory judgments, as compared to a group of older adults who experienced the identical study and test conditions. Critically, however, when memory performance was made comparable between the AD patients and the older adults (e.g., by giving AD patients extra exposures to the study materials), AD patients were still greatly impaired at monitoring the likely accuracy of their recognition and source judgments. This result indicates that the monitoring impairment in AD patients is actually worse than their memory impairment, as otherwise there would have been no differences between the two groups in monitoring performance when there were no differences in accuracy. We discuss the brain correlates of this memory-monitoring deficit and also propose a Remembrance-Evaluation model of memory-monitoring.

  4. Subcortical Shape Changes, Hippocampal Atrophy and Cortical Thinning in Future Alzheimer's Disease Patients.

    PubMed

    Kälin, Andrea M; Park, Min T M; Chakravarty, M Mallar; Lerch, Jason P; Michels, Lars; Schroeder, Clemens; Broicher, Sarah D; Kollias, Spyros; Nitsch, Roger M; Gietl, Anton F; Unschuld, Paul G; Hock, Christoph; Leh, Sandra E

    2017-01-01

    Efficacy of future treatments depends on biomarkers identifying patients with mild cognitive impairment at highest risk for transitioning to Alzheimer's disease. Here, we applied recently developed analysis techniques to investigate cross-sectional differences in subcortical shape and volume alterations in patients with stable mild cognitive impairment (MCI) (n = 23, age range 59-82, 47.8% female), future converters at baseline (n = 10, age range 66-84, 90% female) and at time of conversion (age range 68-87) compared to group-wise age and gender matched healthy control subjects (n = 23, age range 61-81, 47.8% female; n = 10, age range 66-82, 80% female; n = 10, age range 68-82, 70% female). Additionally, we studied cortical thinning and global and local measures of hippocampal atrophy as known key imaging markers for Alzheimer's disease. Apart from bilateral striatal volume reductions, no morphometric alterations were found in cognitively stable patients. In contrast, we identified shape alterations in striatal and thalamic regions in future converters at baseline and at time of conversion. These shape alterations were paralleled by Alzheimer's disease like patterns of left hemispheric morphometric changes (cortical thinning in medial temporal regions, hippocampal total and subfield atrophy) in future converters at baseline with progression to similar right hemispheric alterations at time of conversion. Additionally, receiver operating characteristic curve analysis indicated that subcortical shape alterations may outperform hippocampal volume in identifying future converters at baseline. These results further confirm the key role of early cortical thinning and hippocampal atrophy in the early detection of Alzheimer's disease. But first and foremost, and by distinguishing future converters but not patients with stable cognitive abilities from cognitively normal subjects, our results support the value of early subcortical shape alterations and reduced hippocampal

  5. Subcortical Shape Changes, Hippocampal Atrophy and Cortical Thinning in Future Alzheimer's Disease Patients

    PubMed Central

    Kälin, Andrea M.; Park, Min T. M.; Chakravarty, M. Mallar; Lerch, Jason P.; Michels, Lars; Schroeder, Clemens; Broicher, Sarah D.; Kollias, Spyros; Nitsch, Roger M.; Gietl, Anton F.; Unschuld, Paul G.; Hock, Christoph; Leh, Sandra E.

    2017-01-01

    Efficacy of future treatments depends on biomarkers identifying patients with mild cognitive impairment at highest risk for transitioning to Alzheimer's disease. Here, we applied recently developed analysis techniques to investigate cross-sectional differences in subcortical shape and volume alterations in patients with stable mild cognitive impairment (MCI) (n = 23, age range 59–82, 47.8% female), future converters at baseline (n = 10, age range 66–84, 90% female) and at time of conversion (age range 68–87) compared to group-wise age and gender matched healthy control subjects (n = 23, age range 61–81, 47.8% female; n = 10, age range 66–82, 80% female; n = 10, age range 68–82, 70% female). Additionally, we studied cortical thinning and global and local measures of hippocampal atrophy as known key imaging markers for Alzheimer's disease. Apart from bilateral striatal volume reductions, no morphometric alterations were found in cognitively stable patients. In contrast, we identified shape alterations in striatal and thalamic regions in future converters at baseline and at time of conversion. These shape alterations were paralleled by Alzheimer's disease like patterns of left hemispheric morphometric changes (cortical thinning in medial temporal regions, hippocampal total and subfield atrophy) in future converters at baseline with progression to similar right hemispheric alterations at time of conversion. Additionally, receiver operating characteristic curve analysis indicated that subcortical shape alterations may outperform hippocampal volume in identifying future converters at baseline. These results further confirm the key role of early cortical thinning and hippocampal atrophy in the early detection of Alzheimer's disease. But first and foremost, and by distinguishing future converters but not patients with stable cognitive abilities from cognitively normal subjects, our results support the value of early subcortical shape alterations and reduced

  6. [Proceeding memory in Alzheimer's disease].

    PubMed

    Arroyo-Anlló, Eva Ma; Chamorro-Sánchez, Jorge; Díaz-Marta, Juan Poveda; Gil, Roger

    2013-01-01

    Procedural learning can acquire or develop skills through performance and repetition of a task unconsciously or unintentionally. Procedural skills are considered as the cornerstone in the neuropsychological rehabilitation to promote the autonomy of patients with brain damage, as those with Alzheimer's disease. This review presents data about procedural skills in Alzheimer's disease. Over the past three decades, we have found 40 articles studying various procedural skills in the Alzheimer's disease: motor, perceptual-motor, cognitive, perceptual-cognitive and those developed through serial reaction-time paradigm. We analyzed every study evaluating a procedural skill, indicating the used task and preservation or no preservation of procedural learning. Overall, most of the papers published describe conservation of learning procedures or relatively conserved in Alzheimer's disease, which could be used to promote patient autonomy.

  7. Visual evoked potentials in dementia: a meta-analysis and empirical study of Alzheimer's disease patients.

    PubMed

    Pollock, V E; Schneider, L S; Chui, H C; Henderson, V; Zemansky, M; Sloane, R B

    1989-04-15

    A meta-analytic review of flash and pattern reversal visual evoked potential research indicates that elderly demented patients have longer P100 latencies than age-matched control subjects. In the present empirical research, patients with research diagnoses of probable Alzheimer's disease were compared with sex- and age-matched control subjects using P100 latencies of visual evoked potentials (VEP) elicited by flash and pattern reversal. As compared to control subjects, Alzheimer's disease patients showed significantly longer P100 latencies of the VEP elicited by pattern reversal; the flash P100 only marginally distinguished them. These findings are discussed within the context of VEP recording practices, patient selection, sex and age matching of control subjects, and the visual system.

  8. Familiar music as an enhancer of self-consciousness in patients with Alzheimer's disease.

    PubMed

    Arroyo-Anlló, Eva M; Díaz, Juan Poveda; Gil, Roger

    2013-01-01

    The main objective of this paper is to examine the impact of familiar music on self-consciousness (SC) in patients with Alzheimer's disease (AD). For this purpose, two AD groups of 20 patients matched by age, educational level, gender, illness duration, and cognitive state were assessed using an SC questionnaire before and after music intervention. The SC questionnaire measured several aspects: personal identity, anosognosia, affective state, body representation, prospective memory, introspection and moral judgments. One AD group received familiar music stimulation and another AD group unfamiliar music stimulation over three months. The AD patients who received a familiar music intervention showed a stabilization or improvement in aspects of SC. By contrast, control AD group showed a deterioration of most of the SC aspects after unfamiliar music stimulation, except the SC aspects of body representation and affective state. Familiar music stimulation could be considered as an enhancer of SC in patients with Alzheimer's disease.

  9. Immunotherapy for Alzheimer disease.

    PubMed

    Gouras, Gunnar K

    2009-01-01

    Immunotherapy approaches for Alzheimer disease currently are among the leading therapeutic directions for the disease. Active and passive immunotherapy against the beta-amyloid peptides that aggregate and accumulate in the brain of those afflicted by the disease have been shown by numerous groups to reduce plaque pathology and improve behavior in transgenic mouse models of the disease. Several ongoing immunotherapy clinical trials for Alzheimer disease are in progress. The background and ongoing challenges for these immunological approaches for the treatment of Alzheimer disease are discussed.

  10. Head trauma and Alzheimer's disease.

    PubMed

    Nandoe, Rishi D S; Scheltens, Philip; Eikelenboom, Piet

    2002-08-01

    The authors describe a case of a 55 year old woman who was diagnosed with Alzheimer's disease 1.5 years after a car accident in which she experienced a mild concussion. Extensive history taking disclosed no cognitive changes prior to the car accident. The case is discussed in view of the inflammation hypothesis regarding Alzheimer's disease and the role of the apolipoprotein E4 genotype of the patient.

  11. Sexuality in patients with Parkinson's disease, Alzheimer's disease, and other dementias.

    PubMed

    Bronner, Gila; Aharon-Peretz, Judith; Hassin-Baer, Sharon

    2015-01-01

    Sexual dysfunction (SD) is common among patients with Parkinson's disease (PD), Alzheimer's disease (AD), and other dementias. Sexual functioning and well-being of patients with PD and their partners are affected by many factors, including motor disabilities, non-motor symptoms (e.g., autonomic dysfunction, sleep disturbances, mood disorders, cognitive abnormalities, pain, and sensory disorders), medication effects, and relationship issues. The common sexual problems are decreased desire, erectile dysfunction, difficulties in reaching orgasm, and sexual dissatisfaction. Hypersexuality is one of a broad range of impulse control disorders reported in PD, attributed to antiparkinsonian therapy, mainly dopamine agonists. Involvement of a multidisciplinary team may enable a significant management of hypersexuality. Data on SD in demented patients are scarce, mainly reporting reduced frequency of sex and erectile dysfunction. Treatment of SD is advised at an early stage. Behavioral problems, including inappropriate sexual behavior (ISB), are distressing for patients and their caregivers and may reflect the prevailing behavior accompanying dementia (disinhibition or apathy associated with hyposexuality). The neurobiologic basis of ISB is still only vaguely understood but assessment and intervention are recommended as soon as ISB is suspected. Management of ISB in dementia demands a thorough evaluation and understanding of the behavior, and can be treated by non-pharmacologic and pharmacologic interventions.

  12. Alzheimer disease update.

    PubMed

    Matthews, Brandy R

    2010-04-01

    Alzheimer disease (AD) is a progressive neurodegenerative disorder affecting more than 37 million people worldwide and increasing in incidence based on its primary risk factor, advancing age. A growing body of knowledge regarding amyloid and tau neuropathology, genetic and environmental risk modifiers, early and atypical clinical presentations, and the use of symptom-modifying medical and psychosocial therapies is available to aid in the diagnosis and management of patients with AD. Exciting recent advances in neurobiology render the areas of genetic susceptibility, biomarkers for early disease detection and assessment of disease progression, and novel therapeutic strategies to modify the natural history of the disease compelling, but in need of further study before implementation into routine clinical practice is feasible.

  13. Total glutamine synthetase levels in cerebrospinal fluid of Alzheimer's disease patients are unchanged.

    PubMed

    Timmer, Nienke M; Herbert, Megan K; Claassen, Jurgen A H R; Kuiperij, H Bea; Verbeek, Marcel M

    2015-03-01

    Decreased cerebral protein and activity levels of glutamine synthetase (GS) have been reported for Alzheimer's disease (AD) patients. Using a recently established method, we quantified total GS levels in cerebrospinal fluid (CSF) from AD patients and control subjects. Furthermore, we investigated if total GS levels in CSF could differentiate AD from frontotemperal dementia and dementia with Lewy bodies patients. As we found no significantly altered total GS levels in any of the patient groups compared with control subjects, we conclude that levels of total GS in CSF have no diagnostic value for AD, dementia with Lewy bodies, or frontotemperal dementia.

  14. [Language Symptoms of Alzheimer's Disease].

    PubMed

    Shinagawa, Shunichiro

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative disorder mainly characterized by progressive memory disturbance. Language symptoms are considered to be less disease specific and therefore did not attract many researchers, interest until recently. Typical patients with AD present amnesic aphasia in the early disease stage followed by transcortical sensory aphasia; however, their language symptoms are varied. Recently, the concept of logopenic variant of primary progressive aphasia (PPA) has been developed, which is reported to have Alzheimer's neuropathology. Clinicians should verify patients' language abilities, as language can be the key to reveal their true cognitive functions.

  15. Role of methylglyoxal in Alzheimer's disease.

    PubMed

    Angeloni, Cristina; Zambonin, Laura; Hrelia, Silvana

    2014-01-01

    Alzheimer's disease is the most common and lethal neurodegenerative disorder. The major hallmarks of Alzheimer's disease are extracellular aggregation of amyloid β peptides and, the presence of intracellular neurofibrillary tangles formed by precipitation/aggregation of hyperphosphorylated tau protein. The etiology of Alzheimer's disease is multifactorial and a full understanding of its pathogenesis remains elusive. Some years ago, it has been suggested that glycation may contribute to both extensive protein cross-linking and oxidative stress in Alzheimer's disease. Glycation is an endogenous process that leads to the production of a class of compounds known as advanced glycation end products (AGEs). Interestingly, increased levels of AGEs have been observed in brains of Alzheimer's disease patients. Methylglyoxal, a reactive intermediate of cellular metabolism, is the most potent precursor of AGEs and is strictly correlated with an increase of oxidative stress in Alzheimer's disease. Many studies are showing that methylglyoxal and methylglyoxal-derived AGEs play a key role in the etiopathogenesis of Alzheimer's disease.

  16. Cerebrospinal Fluid from Alzheimer's Disease Patients Contains Fungal Proteins and DNA.

    PubMed

    Alonso, Ruth; Pisa, Diana; Rábano, Alberto; Rodal, Izaskun; Carrasco, Luis

    2015-01-01

    The identification of biomarkers for Alzheimer's disease is important for patient management and to assess the effectiveness of clinical intervention. Cerebrospinal fluid (CSF) biomarkers constitute a powerful tool for diagnosis and monitoring disease progression. We have analyzed the presence of fungal proteins and DNA in CSF from AD patients. Our findings reveal that fungal proteins can be detected in CSF with different anti-fungal antibodies using a slot-blot assay. Additionally, amplification of fungal DNA by PCR followed by sequencing distinguished several fungal species. The possibility that these fungal macromolecules could represent AD biomarkers is discussed.

  17. Observed behaviors of patients with probable Alzheimer's disease who are hospitalized for diagnostic tests.

    PubMed

    Day, N; Musallam, K; Wells, M

    1999-11-01

    This study examines observed behaviors of hospitalized patients with probable Alzheimer's disease (AD) undergoing invasive diagnostic procedures. Data was obtained from nursing documentation in the medical records of 30 patients, 10 in each stage of AD (i.e., mild, moderate, severe). In general, analysis of the data revealed that changes in behavior occurred immediately prior to, during, and following these procedures. Specifically, the moderately impaired patients showed the most significant curve over the 5-day observation period, while patients in the mildly impaired group showed a high peak of behavioral change on the test day. The severely impaired group of patients had a higher sustained level of activity throughout the 5-day period. Routine assessment of the patients' usual behaviors, care-givers' knowledge of the stage of disease, and awareness of the potential impact that diagnostics may have on cognitively impaired patients could help care providers decide what interventions most likely would lead to successful outcomes.

  18. [Hearing loss and Alzheimer's disease].

    PubMed

    Bakhos, David; Villeuneuve, Alexandre; Kim, Soo; Hammoudi, Karim; Hommet, Caroline

    2015-06-01

    Recent studies suggest that subjects with hearing loss are more likely to develop Alzheimer's disease. Hearing loss can be consecutive to presbycusis and/or to central auditory dysfunction. Standard audiometric measures (pure tone and speech intelligibility) allow the diagnosis of presbycusis. However, to demonstrate central auditory dysfunction, specific audiometric tests are needed such as noisy and/or dichotic tests. Actually, no consensus exists to investigate hearing loss in people with Alzheimer's disease though hearing loss may be an early manifestation of Alzheimer's disease. Until now, investigations and clinical procedure related to the diagnosis of Alzheimer's disease ignored the hearing ability of the patient. However, the major part of care management and investigations implies the patient's communication ability with the caregivers. Hearing loss may be one of the most unrecognized deficit in subjects with Alzheimer's disease. Auditory rehabilitation could benefit to the patient in order to lessen cognitive decline, but this must be investigated during longitudinal studies in order to clearly demonstrate their efficiency.

  19. Skill learning in patients with moderate Alzheimer's disease: a prospective pilot-study of waltz-lessons.

    PubMed

    Rösler, Alexander; Seifritz, Erich; Kräuchi, Kurt; Spoerl, David; Brokuslaus, Ilona; Proserpi, Sara-Maria; Gendre, Annekäthi; Savaskan, Egemen; Hofmann, Marc

    2002-12-01

    The authors report the effect of a 12-day prospective, blinded dance-learning trial in 5 patients with moderate Alzheimer's disease (AD) and 5 age-matched depressed patients. Patients with AD showed a significant effect in procedural learning whereas depressed patients did not. These findings suggest potential implications for therapeutic interventions in patients with moderate AD.

  20. Progress Report on Alzheimer Disease: Volume III.

    ERIC Educational Resources Information Center

    National Inst. on Aging (DHHS/PHS), Bethesda, MD.

    This report summarizes advances in the understanding of Alzheimer's disease, the major cause of mental disability among older Americans. The demography of the disease is discussed, noting that approximately 2.5 million American adults are afflicted with the disease and that the large increase in the number of Alzheimer's disease patients is due to…

  1. Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer's disease.

    PubMed

    Chételat, Gaël; Ossenkoppele, Rik; Villemagne, Victor L; Perrotin, Audrey; Landeau, Brigitte; Mézenge, Florence; Jagust, William J; Dore, Vincent; Miller, Bruce L; Egret, Stéphanie; Seeley, William W; van der Flier, Wiesje M; La Joie, Renaud; Ames, David; van Berckel, Bart N M; Scheltens, Philip; Barkhof, Frederik; Rowe, Christopher C; Masters, Colin L; de La Sayette, Vincent; Bouwman, Femke; Rabinovici, Gil D

    2016-09-01

    See O'Sullivan and Vann (doi:10.1093/aww166) for a scientific commentary on this article.About 15% of patients clinically diagnosed with Alzheimer's disease do not show high tracer retention on amyloid positon emission tomography imaging. The present study investigates clinical and demographic features, patterns of brain atrophy and hypometabolism and longitudinal clinical trajectories of these patients. Forty amyloid-negative patients carrying a pre-scan diagnosis of Alzheimer's disease dementia from four centres were included (11/29 females/males; mean age = 67 ± 9). Detailed clinical histories, including the clinical diagnoses before and after the amyloid scan and at follow-up, were collected. Patients were classified according to their pre-scan clinical phenotype as amnestic (memory predominant), non-amnestic (predominant language, visuospatial or frontal symptoms), or non-specific (diffuse cognitive deficits). Demographic, clinical, neuropsychological, magnetic resonance imaging and (18)F-fluorodeoxyglucose positon emission tomography data were compared to 27 amyloid-positive typical Alzheimer's disease cases (14/13 females/males; mean age = 71 ± 10) and 29 amyloid-negative controls (15/14 females/males; mean age = 69 ± 12) matched for age, gender and education. There were 21 amnestic, 12 non-amnestic, and seven non-specific amyloid-negative Alzheimer's disease cases. Amyloid-negative subgroups did not differ in age, gender or education. After the amyloid scan, clinicians altered the diagnosis in 68% of amyloid-negative patients including 48% of amnestic versus 94% of non-amnestic and non-specific cases. Amnestic amyloid-negative cases were most often reclassified as frontotemporal dementia, non-amnestic as frontotemporal dementia or corticobasal degeneration, and non-specific as dementia with Lewy bodies or unknown diagnosis. The longer-term clinical follow-up was consistent with the post-scan diagnosis in most cases (90%), including in amnestic amyloid

  2. [Management of Alzheimer disease].

    PubMed

    Belmin, Joël; Péquignot, Renaud; Konrat, Cécile; Pariel-Madjlessi, Sylvie

    2007-10-01

    Management of Alzheimer disease is based on drug and nondrug treatments. Specific drug treatment includes acetylcholinesterase inhibitors and memantine. They show moderate efficacy superior to that of placebo for global condition, cognitive disorders, need for care, and behavioral problems, but do not prevent further decline. These treatments remain underused. The efficacy of psychotropic drugs (antidepressants, neuroleptics, and antipsychotic agents) in treating behavioral problems is not well documented. Nondrug activities and interventions have not been sufficiently evaluated scientifically. These involve interventions against the consequences of the disease (loss of autonomy, malnutrition) and helping patients' family caregivers. Among these activities, the best evaluated and most interesting are: educational programs for caregivers, occupational therapy at home, and interventions at home by nurses specially trained as case managers.

  3. The use of errorless learning strategies for patients with Alzheimer's disease: a literature review.

    PubMed

    Li, Ruijie; Liu, Karen P Y

    2012-12-01

    The aim of this article was to review the evidence of errorless learning on learning outcomes in patients with early-stage Alzheimer's disease. A computer-aided literature search from 1999 to 2011 was carried out using MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and PsycArticles. Keywords included 'errorless learning or practice' and 'Alzheimer's disease'. Four studies that fulfilled the inclusion criteria were selected and reviewed. Two of the studies were clinical controlled trials: one was a single-group pretest-post-test trial and the other was a multiple single-participant study. Demographic variables, design, treatment and outcome measures were summarized. Recall trials were used as the primary outcome measure. Results indicate that the use of errorless learning promotes better retention of specific types of information. Errorless learning is effective in memory rehabilitation of older adults with Alzheimer's disease. However, it would require more studies with unified outcome measures to allow for the formulation of standardized clinical protocol and recommendations.

  4. [Relationships between weight loss and circulating cytokines in patients with Alzheimer's disease].

    PubMed

    Mahieux, Florence; Couderc, Rémy; Fénelon, Gilles; Maachi, Mustapha

    2006-12-01

    106 consecutive patients with Alzheimer's disease living in the community were examined in a memory clinic from a neurological department. They were screened for weight loss over the last 2 years. Age, duration of the disease, behavioral disorders, mini mental status examination, body mass index were recorded. Tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), interleukin 6 (IL-6) and interleukin 2 (IL-2) blood levels were measured. Weight loss was reported in 42.5% of the patients. TNFalpha levels were significantly higher in these patients (18.8 versus 15.8 pg/mL; p=0.04) than in patients without weight loss. Weight loss was also associated with a lower MMSE score (16.9 versus 19.3; p=0.03), current pacing (20% versus 1.6%; p=0.002), and hallucinations (20.0% versus 3.3%; p=0.008). The levels of the other cytokines did not differ between the patients with and without weight loss. Our findings suggest an association between high levels of circulating TNFalpha and unexplained weight loss in Alzheimer's disease.

  5. Longitudinal study of cerebrospinal fluid amyloid proteins and apolipoprotein E in patients with probable Alzheimer's disease.

    PubMed

    Pirttilä, T; Koivisto, K; Mehta, P D; Reinikainen, K; Kim, K S; Kilkku, O; Heinonen, E; Soininen, H; Riekkinen, P; Wisniewski, H M

    1998-06-12

    Levels of soluble amyloid beta protein (sAbeta), amyloid beta precursor protein (APP) and apolipoprotein E (apoE) were examined in cerebrospinal fluid (CSF) obtained twice, at baseline and after 3-year follow-up, from 25 patients with probable Alzheimer's disease (AD). Levels of sAbeta and apoE from patients with the apoE4 allele decreased with time, whereas the levels were similar in patients without apoE4 allele. Changes of sAbeta and apoE concentrations correlated significantly with those of mini-mental state examination (MMSE) scores. Levels of sAbeta did not change with time in patients with mild dementia, whereas they decreased significantly in patients with moderate dementia. ApoE concentrations decreased in both groups whereas APP levels were similar. We conclude that measurements of CSF sAbeta and apoE levels may be helpful in monitoring progression of the disease.

  6. Neuroinflammation in Alzheimer's disease.

    PubMed

    Heneka, Michael T; Carson, Monica J; El Khoury, Joseph; Landreth, Gary E; Brosseron, Frederic; Feinstein, Douglas L; Jacobs, Andreas H; Wyss-Coray, Tony; Vitorica, Javier; Ransohoff, Richard M; Herrup, Karl; Frautschy, Sally A; Finsen, Bente; Brown, Guy C; Verkhratsky, Alexei; Yamanaka, Koji; Koistinaho, Jari; Latz, Eicke; Halle, Annett; Petzold, Gabor C; Town, Terrence; Morgan, Dave; Shinohara, Mari L; Perry, V Hugh; Holmes, Clive; Bazan, Nicolas G; Brooks, David J; Hunot, Stéphane; Joseph, Bertrand; Deigendesch, Nikolaus; Garaschuk, Olga; Boddeke, Erik; Dinarello, Charles A; Breitner, John C; Cole, Greg M; Golenbock, Douglas T; Kummer, Markus P

    2015-04-01

    Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.

  7. Characteristics of Alzheimer's disease among patients in Taiwan, Hong Kong, and Beijing.

    PubMed

    Yang, Yuan-Han; Wang, Huali; Lam, Linda; Chan, Wai-Chi; Yu, Xin; Li, Tao; Wang, Wen-Fu; Chiu, Pai-Yi; Lin, Yu-Te; Hu, Chaur-Jong; Fuh, Jong-Ling; Morris, John C

    2014-01-01

    In order to obtain data from patients with Alzheimer's disease dementia and their informants in a uniform manner and to foster further research among the Chinese and other races, we have conducted an international study to recruit patients diagnosed with Alzheimer's disease (AD) from Taiwan, Hong Kong, and Beijing. The Uniform Data Set was translated into Chinese and administrated to AD patients and their informants. A total of 1,107 AD dementia patients were recruited, including 691 from Taiwan, 244 from Beijing, and 172 from Hong Kong. There were differences in the AD patients: gender (p = 0.099), education (p < 0.001), age (p < 0.001), and handedness (p = 0.007). For informants, age (p = 0.679), gender (p = 0.117), education (p < 0.001), and living together or not (p < 0.001) differed in the three samples. Although three areas across the Taiwan Strait are ethnic Chinese, the clinical picture for patients and informants are very different. Further study is needed to clarify the significance of clinical characteristics in Chinese societies.

  8. Effects of hypertension and hypercholesterolemia on cognitive functioning in patients with alzheimer disease.

    PubMed

    Goldstein, Felicia C; Ashley, Angela V; Endeshaw, Yohannes W; Hanfelt, John; Lah, James J; Levey, Allan I

    2008-01-01

    This study investigated the relationship between the vascular comorbidities (VCs) of hypertension and hypercholesterolemia and the cognitive phenotype of Alzheimer disease (AD). Seventy-four AD patients underwent objective measurement of blood pressure and serum cholesterol levels, and they received a detailed neuropsychologic evaluation examining attention, memory, language, visuomotor/visuospatial skills, and executive functioning. Multiple regression analyses controlling for demographic variables, overall cognitive status, and the presence of diabetes/cardiac disease indicated that an increase in the number of VCs, but not their severity, was associated with poorer verbal and visual recall, visuoconstructive and spatial analysis, verbal reasoning, and set shifting. The findings demonstrate that VCs are associated with specific aspects of cognitive functioning in AD patients. The mechanisms likely involve the effects of VCs on cerebrovascular disease including white matter disruption. The results highlight the importance of controlling these risk factors in patients who carry the diagnosis of AD.

  9. Concordance of occupational and environmental exposure information elicited from patients with Alzheimer's disease and surrogate respondents

    SciTech Connect

    Chong, J.P.; Turpie, I.; Haines, T.; Muir, G.; Farnworth, H.; Cruttenden, K.; Julian, J.; Verma, D.; Hillers, T.

    1989-01-01

    Identification of risk factors for Alzheimer's disease through the use of well designed case-control studies has been described as a research priority. Increasing recognition of the neurotoxic potential of many industrial chemicals such as organic solvents raises the question of the occupational and environmental contribution to the etiology of this high-priority health problem. The intention of this study was to develop and evaluate a methodology that could be used in a large scale case-control study of the occupational and environmental risk factors for dementia or a population-based surveillance system for neurotoxic disorders. The specific objectives of this study were to investigate: (1) the reliability of exposure-eliciting, interviewer-administered questionnaires given to patients with Alzheimer's disease (SDAT); (2) the reliability of exposure-eliciting interviewer-administered questionnaires given to the family of patients with SDAT and the agreement with the responses of the patient or surrogate respondents; (3) the reliability and agreement of responses of age- and sex-matched control patients and their families selected from geriatric care institutions and the community, with respect to the same exposure-eliciting and interviewer-administered questionnaire; and (4) the reliability of agent-based exposure ascertainment by a single, trained rater. The results of the study demonstrate that occupational and environmental histories from which exposure information can be derived is most reliably elicited from job descriptions of cases and control subjects rather than job titles alone or detailed probes for potential neurotoxic exposures. This will necessitate the use of standardized interviewer-administered instruments to derive this information in case-control studies of Alzheimer's disease or population-based surveillance systems for occupational and environmental neurotoxicity.

  10. Amyloid beta peptide immunotherapy in Alzheimer disease.

    PubMed

    Delrieu, J; Ousset, P J; Voisin, T; Vellas, B

    2014-12-01

    Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β peptide represents an important molecular target for intervention in Alzheimer's disease. The main purpose of this work is to review immunotherapy studies in relation to the Alzheimer's disease. Several types of amyloid β peptide immunotherapy for Alzheimer's disease are under investigation, active immunization and passive administration with monoclonal antibodies directed against amyloid β peptide. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not show significant cognitive effect for the moment. Currently, several amyloid β peptide immunotherapy approaches are under investigation but also against tau pathology. Results from amyloid-based immunotherapy studies in clinical trials indicate that intervention appears to be more effective in early stages of amyloid accumulation in particular solanezumab with a potential impact at mild Alzheimer's disease, highlighting the importance of diagnosing Alzheimer's disease as early as possible and undertaking clinical trials at this stage. In both phase III solanezumab and bapineuzumab trials, PET imaging revealed that about a quarter of patients lacked fibrillar amyloid pathology at baseline, suggesting that they did not have Alzheimer's disease in the first place. So a new third phase 3 clinical trial for solanezumab, called Expedition 3, in patients with mild Alzheimer's disease and evidence of amyloid burden has been started. Thus, currently, amyloid intervention is realized at early stage of the Alzheimer's disease in clinical trials, at prodromal Alzheimer's disease, or at asymptomatic subjects or at risk to develop Alzheimer's disease and or at asymptomatic subjects with autosomal dominant mutation.

  11. Epidemiology of Alzheimer disease.

    PubMed

    Mayeux, Richard; Stern, Yaakov

    2012-08-01

    The global prevalence of dementia has been estimated to be as high as 24 million, and is predicted to double every 20 years until at least 2040. As the population worldwide continues to age, the number of individuals at risk will also increase, particularly among the very old. Alzheimer disease is the leading cause of dementia beginning with impaired memory. The neuropathological hallmarks of Alzheimer disease include diffuse and neuritic extracellular amyloid plaques in brain that are frequently surrounded by dystrophic neurites and intraneuronal neurofibrillary tangles. The etiology of Alzheimer disease remains unclear, but it is likely to be the result of both genetic and environmental factors. In this review we discuss the prevalence and incidence rates, the established environmental risk factors, and the protective factors, and briefly review genetic variants predisposing to disease.

  12. Significance of lutein in red blood cells of Alzheimer's disease patients.

    PubMed

    Kiko, Takehiro; Nakagawa, Kiyotaka; Tsuduki, Tsuyoshi; Suzuki, Toshihide; Arai, Hiroyuki; Miyazawa, Teruo

    2012-01-01

    Red blood cells (RBC) of Alzheimer's disease (AD) patients are known to be in an excessively oxidized state (i.e., with a high accumulation of peroxidized phospholipids (PLOOH)). Previously we confirmed in vitro, in vivo murine, and in human studies that carotenoids can effectively inhibit accumulation of RBC PLOOH. Thus, the relationship between RBC carotenoids and PLOOH concentrations in AD patients is of interest. In this study, RBC carotenoids and PLOOH were evaluated in 28 normal control subjects (age: 74.1 ± 1.3 years) and 28 patients with AD (age: 72.5 ± 1.4 years). The concentrations of RBC carotenoids, especially lutein, in AD patients were significantly lower than in control subjects. An inverse relationship was seen between RBC carotenoids, especially lutein, and PLOOH concentrations in AD patients. These results suggest that RBC lutein, in particular, may contribute to suppression of PLOOH accumulation in RBC of AD patients.

  13. Histopathology and Florbetaben PET in Patients Incorrectly Diagnosed with Alzheimer's Disease.

    PubMed

    Sabbagh, Marwan N; Schäuble, Barbara; Anand, Keshav; Richards, Danielle; Murayama, Shigeo; Akatsu, Hiroyasu; Takao, Masaki; Rowe, Christopher C; Masters, Colin L; Barthel, Henryk; Gertz, Hermann-Josef; Peters, Oliver; Rasgon, Natalie; Jovalekic, Aleksandar; Sabri, Osama; Schulz-Schaeffer, Walter J; Seibyl, John

    2017-01-01

    Of 57 individuals diagnosed with Alzheimer's disease (AD) in a phase III study, 13 (23%) had amyloid-β (Aβ) levels on postmortem histopathology that did not explain the dementia. Based on postmortem histopathology, a wide range of different non-AD conditions was identified, including frontotemporal dementia, hippocampal sclerosis, and dementia with Lewy bodies. Of the histopathologically Aβ negative scored cases ante-mortem Florbetaben PET scans were classified as negative for Aβ in 11 patients based on visual analysis and in all 12 quantifiable cases based on composite standardized uptake value ratios. Thus, florbetaben PET can assist physicians in the differential diagnosis of neurodegenerative disorders by reliably excluding Aβ pathology.

  14. Frontal defects contribute to the genesis of closing-in in Alzheimer's disease patients.

    PubMed

    De Lucia, Natascia; Grossi, Dario; Maria Fasanaro, Angiola; Carpi, Sabrina; Trojano, Luigi

    2013-08-01

    Closing-in (CI) refers to copying drawings near to or superimposed on the original model, and is often observed in Alzheimer's disease (AD) patients. Contrasting hypotheses have been suggested to explain CI, but no prospective study has directly verified these interpretations. We evaluated the role of frontal/executive versus visuo-spatial impairments in a prospective sample of AD patients, and also explored whether different types of CI are related to specific neuropsychological tasks. We enrolled 64 AD patients who underwent copying tasks and an extensive neuropsychological assessment of visuo-spatial and visuo-constructional skills, frontal/executive abilities and anterograde memory. AD patients with CI showed more severe impairment on frontal/executive functions than AD patients without CI. Moreover, the tendency to produce copies superimposed on the model was selectively associated with poor inhibitory control for irrelevant responses. On this basis, we suggest that different CI phenomena could be ascribed to distinctive frontal/executive defects.

  15. Discrepancy between subjective autobiographical reliving and objective recall: The past as seen by Alzheimer's disease patients.

    PubMed

    El Haj, Mohamad; Antoine, Pascal

    2017-03-01

    This paper investigated whether Alzheimer's disease (AD) patients may demonstrate a discrepancy between subjective autobiographical reliving and objective recall. To this end, 31 AD patients and 35 controls were asked to retrieve three autobiographical memories. For each memory, participants were asked to rate its subjective characteristics (e.g., reliving, travel in time, visual imagery…). Besides this subjective assessment, we analyzed recall objectively with regard to specificity. Results showed poorer subjective autobiographical reliving and objective recall in AD patients than in controls. A discrepancy (i.e., higher level of subjective reliving than of objective recall) was observed in AD but not in control participants. Despite a compromise in their objective recall, AD patients seemed to attribute a high value to their subjective autobiographical experience. This discrepancy can be attributed to a potential genuine consciousness experience in which mild AD patients can, to some extent, experience some subjective features of the past.

  16. The picture superiority effect in patients with Alzheimer's disease and mild cognitive impairment.

    PubMed

    Ally, Brandon A; Gold, Carl A; Budson, Andrew E

    2009-01-01

    The fact that pictures are better remembered than words has been reported in the literature for over 30 years. While this picture superiority effect has been consistently found in healthy young and older adults, no study has directly evaluated the presence of the effect in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). Clinical observations have indicated that pictures enhance memory in these patients, suggesting that the picture superiority effect may be intact. However, several studies have reported visual processing impairments in AD and MCI patients which might diminish the picture superiority effect. Using a recognition memory paradigm, we tested memory for pictures versus words in these patients. The results showed that the picture superiority effect is intact, and that these patients showed a similar benefit to healthy controls from studying pictures compared to words. The findings are discussed in terms of visual processing and possible clinical importance.

  17. Alzheimer disease and anesthesia.

    PubMed

    Inan, Gözde; Özköse Satirlar, Zerrin

    2015-01-01

    Alzheimer disease (AD) is one of the most common neurodegenerative diseases and the most prevalent form of dementia. Some factors in the development of AD, age being the best-known one, have been suggested; however, no causes have been found yet. The pathophysiology of the disease is highly complex, current therapies are palliative, and a cure is still lacking. Adverse effects of anesthetics in the elderly have been reported since the 1950s; however, awareness of this old problem has recently gained inportance again. Whether exposure to surgery and general anesthesia (GA) is associated with the development of AD has been questioned. As the population is aging, many elderly patients will need to be anesthetized, and maybe some were already anesthetized before they were diagnosed. Exposure to anesthetics has been demonstrated to promote pathogenesis of AD in both in vitro and in vivo studies. However, to date, there have not been any clinical trials to address a link between exposure to GA and the development of AD in humans. Therefore, before making any conclusions we need further studies, but we should be aware of the potential risks and take cautions with vulnerable elderly patients.

  18. Down Syndrome and Alzheimer's Disease

    MedlinePlus

    ... as a Therapeutic Target in Alzheimer's Disease 2007 Michael Vitek Novel Therapeutic Reduces Abeta Deposition and Alzheimer's ... Disease Read past editions . Sign up for our e-newsletter Stay up-to-date on the latest ...

  19. The clinical significance of brain microbleeds in patients with Alzheimer's disease: Preliminary study

    PubMed Central

    Heo, Jae-Hyeok; Im, Dong-Gyu; Lee, Seung-Hyeon; Ahn, Jin-Young

    2016-01-01

    Background: Microbleeds (MBs) are observed frequently in Alzheimer's disease (AD) and suggested to play a crucial role in the pathophysiology, but their clinical significance remains unclear. Materials and Methods: The study recruited 100 patients with AD who were diagnosed at the memory clinic in Seoul Medical Center in 2014. For each patient, baseline characteristics, neuropsychological tests, cerebrovascular risk factors, medial temporal lobe atrophy (MTLA), and severity of small vessel disease (SVD) according to the existence of MBs were evaluated. Results: The prevalence of MBs in patients with AD was 33%. The percentage of male gender, the severity of SVD and MTLA were significantly increased in MB(+) group. The MB(+) group showed more severe MTLA and SVD than MB(−) group. Conclusions: These results suggested that MBs might reflect the burden of amyloid and ischemic vascular pathology. PMID:27994360

  20. [Altered identification with relative preservation of emotional prosody production in patients with Alzheimer's disease].

    PubMed

    Templier, Lorraine; Chetouani, Mohamed; Plaza, Monique; Belot, Zoé; Bocquet, Patrick; Chaby, Laurence

    2015-03-01

    Patients with Alzheimer's disease (AD) show cognitive and behavioral disorders, which they and their caregivers have difficulties to cope with in daily life. Psychological symptoms seem to be increased by impaired emotion processing in patients, this ability being linked to social cognition and thus essential to maintain good interpersonal relationships. Non-verbal emotion processing is a genuine way to communicate, especially so for patients whose language may be rapidly impaired. Many studies focus on emotion identification in AD patients, mostly by means of facial expressions rather than emotional prosody; even fewer consider emotional prosody production, despite its playing a key role in interpersonal exchanges. The literature on this subject is scarce with contradictory results. The present study compares the performances of 14 AD patients (88.4±4.9 yrs; MMSE: 19.9±2.7) to those of 14 control subjects (87.5±5.1 yrs; MMSE: 28.1±1.4) in tasks of emotion identification through faces and voices (non linguistic vocal emotion or emotional prosody) and in a task of emotional prosody production (12 sentences were to be pronounced in a neutral, positive, or negative tone, after a context was read). The Alzheimer's disease patients showed weaker performances than control subjects in all emotional recognition tasks and particularly when identifying emotional prosody. A negative relation between the identification scores and the NPI (professional caregivers) scores was found which underlines their link to psychological and behavioral disorders. The production of emotional prosody seems relatively preserved in a mild to moderate stage of the disease: we found subtle differences regarding acoustic parameters but in a qualitative way judges established that the patients' productions were as good as those of control subjects. These results suggest interesting new directions for improving patients' care.

  1. Quality of life in Alzheimer disease: a comparison of patients' and caregivers' points of view.

    PubMed

    Zucchella, Chiara; Bartolo, Michelangelo; Bernini, Sara; Picascia, Marta; Sinforiani, Elena

    2015-01-01

    Unlike in other chronic diseases, the Quality of Life (QoL) of patients affected by Alzheimer Disease (AD) has not been well established, primarily because of the difficulties stemming from the study of patients with cognitive disorders. Because no cure is currently available for AD, the optimization of QoL represents the best possible outcome attainable in all stages of disease, making QoL assessment mandatory. This study identified variables related to patients' QoL and examined the agreement between patients' and caregivers' QoL ratings. A total of 135 dyads (patient and principal caregiver) were enrolled in the study. Patients' QoL evaluations showed a negative relationship with depressive mood and a positive relationship with Activities of Daily Living (ADL), whereas caregivers' QoL ratings showed a negative relationship with patients' depressive mood and behavioral disturbances. Caregivers tended to underestimate patients' QoL compared with the patients' own self-evaluations, with patients' dependency in performing ADL and behavioral disorders as well as caregivers' burdens and depression being the main factors associated with the discrepancy in these evaluations. These findings suggest that the use of proxies as a substitute for the self-report of QoL data should be treated with caution, always accounting for the presence of potential bias.

  2. Genetic insights in Alzheimer's disease.

    PubMed

    Bettens, Karolien; Sleegers, Kristel; Van Broeckhoven, Christine

    2013-01-01

    In the search for new genes in Alzheimer's disease, classic linkage-based and candidate-gene-based association studies have been supplanted by exome sequencing, genome-wide sequencing (for mendelian forms of Alzheimer's disease), and genome-wide association studies (for non-mendelian forms). The identification of new susceptibility genes has opened new avenues for exploration of the underlying disease mechanisms. In addition to detecting novel risk factors in large samples, next-generation sequencing approaches can deliver novel insights with even small numbers of patients. The shift in focus towards translational studies and sequencing of individual patients places each patient's biomaterials as the central unit of genetic studies. The notional shift needed to make the patient central to genetic studies will necessitate strong collaboration and input from clinical neurologists.

  3. Evaluation of patients with Alzheimer's disease before and after dental treatment.

    PubMed

    Rolim, Thaís de Souza; Fabri, Gisele Maria Campos; Nitrini, Ricardo; Anghinah, Renato; Teixeira, Manoel Jacobsen; Siqueira, José Tadeu T de; Cesari, José Augusto Ferrari; Siqueira, Silvia Regina Dowgan Tesseroli de

    2014-12-01

    Oral infections may play a role in Alzheimer's disease (AD). Objective To describe the orofacial pain, dental characteristics and associated factors in patients with Alzheimer's Disease that underwent dental treatment. Method 29 patients with mild AD diagnosed by a neurologist were included. They fulfilled the Mini Mental State Exam and Pfeffer's questionnaire. A dentist performed a complete evaluation: clinical questionnaire; research diagnostic criteria for temporomandibular disorders; McGill pain questionnaire; oral health impact profile; decayed, missing and filled teeth index; and complete periodontal investigation. The protocol was applied before and after the dental treatment. Periodontal treatments (scaling), extractions and topic nystatin were the most frequent. Results There was a reduction in pain frequency (p=0.014), mandibular functional limitations (p=0.011) and periodontal indexes (p<0.05), and an improvement in quality of life (p=0.009) and functional impairment due to cognitive compromise (p<0.001) after the dental treatment. Orofacial complaints and intensity of pain also diminished. Conclusion The dental treatment contributed to reduce co-morbidities associated with AD and should be routinely included in the assessment of these patients.

  4. Goal setting and attainment in Alzheimer's disease patients treated with donepezil

    PubMed Central

    Rockwood, K; Graham, J; Fay, S

    2002-01-01

    Objectives: To understand the treatment goals of Alzheimer's disease (AD) patients, carers, and physicians; to estimate whether clinically important goals are met during treatment with donepezil; and to compare a measure of goal attainment with standard measures used to evaluate AD treatment. Methods: In a 12 month phase IV trial, 108 patients with mild to moderate AD, their primary carers, and treating physicians set goals assigned to five domains, using Goal Attainment Scaling (GAS) as the primary outcome. Goal attainment was assessed quarterly. GAS scores were correlated with standard outcomes, including the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-cog), and the Clinician's Interview-Based Impression of Change-Plus (CIBIC-plus). Results: Physicians set fewer goals (342, mean (SD) per patient=3 (1)) than patients/carers (855, mean=9 (3)), particularly in leisure (20% by physicians compared with 76% by patients/carers), and social interaction (24% versus 49%). Physicians observed statistically significant improvement in global goal attainment for six months, and patients/carers for nine months. Patients/carers described consistent goal attainment, whereas physicians observed variable effects, such as decline in cognition but improved social interaction and behaviour. Physician global GAS scores correlated highly with the CIBIC-plus at weeks 12 (r= -0.82) and 52 (r=-0.80), but not with the ADAS-cog (r=0.12 and r=-0.45, respectively). Patient/carer global GAS scores correlated moderately with the physician's CIBIC-plus (week 12 r=-0.51; week 52 r=-0.56), and nominally with the ADAS-cog. Conclusions: Patients/carers and physicians differ in their expectations and impressions of treatment effects. Clinically important changes correlated only modestly with psychometric tests. Attainment of treatment goals does not accord with a simplistic model in which successful AD treatment means that all declines uniformly improve. PMID:12397141

  5. PIXE analysis of low concentration aluminum in brain tissues of an Alzheimer's disease patient

    NASA Astrophysics Data System (ADS)

    Ishihara, R.; Hanaichi, T.; Takeuchi, T.; Ektessabi, A. M.

    1999-06-01

    An excess accumulation and presence of metal ions may significantly alter a brain cell's normal functions. There have been increasing efforts in recent years to measure and quantify the density and distribution of excessive accumulations of constituent elements (such as Fe, Zn, Cu, and Ca) in the brain, as well as the presence and distribution of contaminating elements (such as Al). This is particularly important in cases of neuropathological disorders such as Alzheimer's disease, Parkinson's disease and ALS. The aim of this paper was to measure the Al present in the temporal cortex of the brain of an Alzheimer's disease patient. The specimens were taken from an unfixed autopsy brain which has been preserved for a period of 4 years in the deep freezer at -80 °C. Proton Induced X-ray Emission Spectroscopy was used for the measurement of Al concentration in this brain tissue. A tandem accelerator with 2 MeV of energy was also used. In order to increase the sensitivity of the signals in the low energy region of the spectra, the absorbers were removed. The results show that the peak height depends on the measurement site. However, in certain cases an extremely high concentration of Al was observed in the PIXE spectra, with an intensity higher than those in the other major elements of the brain's matrix element. Samples from tissues affected by the same disease were analyzed using the EDX analyzer. The results are quantitatively in very good agreement with those of the PIXE analysis.

  6. PIXE analysis of low concentration aluminum in brain tissues of an Alzheimer's disease patient

    SciTech Connect

    Ishihara, R.; Takeuchi, T.; Hanaichi, T.; Ektessabi, A. M.

    1999-06-10

    An excess accumulation and presence of metal ions may significantly alter a brain cell's normal functions. There have been increasing efforts in recent years to measure and quantify the density and distribution of excessive accumulations of constituent elements (such as Fe, Zn, Cu, and Ca) in the brain, as well as the presence and distribution of contaminating elements (such as Al). This is particularly important in cases of neuropathological disorders such as Alzheimer's disease, Parkinson's disease and ALS. The aim of this paper was to measure the Al present in the temporal cortex of the brain of an Alzheimer's disease patient. The specimens were taken from an unfixed autopsy brain which has been preserved for a period of 4 years in the deep freezer at -80 degree sign C. Proton Induced X-ray Emission Spectroscopy was used for the measurement of Al concentration in this brain tissue. A tandem accelerator with 2 MeV of energy was also used. In order to increase the sensitivity of the signals in the low energy region of the spectra, the absorbers were removed. The results show that the peak height depends on the measurement site. However, in certain cases an extremely high concentration of Al was observed in the PIXE spectra, with an intensity higher than those in the other major elements of the brain's matrix element. Samples from tissues affected by the same disease were analyzed using the EDX analyzer. The results are quantitatively in very good agreement with those of the PIXE analysis.

  7. Elevated Galectin-3 Levels in the Serum of Patients With Alzheimer's Disease.

    PubMed

    Wang, Xuexin; Zhang, Shuping; Lin, Faliang; Chu, Wenzheng; Yue, Shouwei

    2015-12-01

    Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system. Galectin-3 (Gal-3) is characterized by a conserved sequence within the carbohydrate recognition domain. The effect of Gal-3 in AD is presently unknown. In this study, we found significantly increased Gal-3 serum levels in patients with AD compared to control participants (P=.017). There was no significant difference between patients with mild cognitive impairment (MCI) and healthy controls (P=.143) or between patients with AD and MCI (P=.688). The degree of cognitive impairment, as measured by the Mini-Mental Status Examination score, was found to have a significant correlation with the Gal-3 serum levels in all patients and healthy controls. These data suggest that Gal-3 potentially plays a role in the neuropathogenesis of AD. The Gal-3 found in serum could be a potential candidate for a biomarker panel for AD diagnosis.

  8. What can we learn from study of Alzheimer's disease in patients with Down syndrome for early-onset Alzheimer's disease in the general population?

    PubMed Central

    2011-01-01

    The clinical and scientific study of dementia in adults with Down syndrome led to the development of the amyloid hypothesis as a fundamental concept in Alzheimer's disease pathogenesis. The journey started with the discovery of the structure and metabolic processing of β-amyloid brain deposits associated with Alzheimer's dementia in adults with Down syndrome, and then the prediction and confirmation of the amyloid precursor protein gene on chromosome 21. The processes and genes responsible for tau hyperphosphorylation contributing to toxic brain deposits were additionally identified. With increasing sophistication in genetic experimental techniques, additional mechanisms associated with excessive amyloid deposits were postulated and tested in brains of people with Down syndrome and Alzheimer's disease and in those with early-onset Alzheimer's disease. This in turn led to the proposal and testing for particular genetic defects associated with familial early-onset Alzheimer's disease. Nearly 200 genetic causes of early-onset types of Alzheimer's disease have since been identified. Only a minority of these causes are on chromosome 21, although the aetiology of excess amyloid production remains fundamental to their pathogenesis. Knowledge of the pathogenic mechanisms of Alzheimer's disease in predisposed families and in people with Down syndrome is a step closer to prevention or cure of this devastating disease. PMID:21542885

  9. Amyloid negativity in patients with clinically diagnosed Alzheimer disease and MCI

    PubMed Central

    Horng, Andy; Fero, Allison; Jagust, William J.

    2016-01-01

    Objective: To examine the clinical and biomarker characteristics of patients with amyloid-negative Alzheimer disease (AD) and mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a prospective cohort study. Methods: We first investigated the reliability of florbetapir− PET in patients with AD and patients with MCI using CSF-Aβ1–42 as a comparison amyloid measurement. We then compared florbetapir− vs florbetapir+ patients with respect to several AD-specific biomarkers, baseline and longitudinal cognitive measurements, and demographic and clinician report data. Results: Florbetapir and CSF-Aβ1–42 +/− status agreed for 98% of ADs (89% of MCIs), indicating that most florbetapir− scans were a reliable representation of amyloid status. Florbetapir− AD (n = 27/177; 15%) and MCI (n = 74/217, 34%) were more likely to be APOE4-negative (MCI 83%, AD 96%) than their florbetapir+ counterparts (MCI 30%, AD 24%). Florbetapir− patients also had less AD-specific hypometabolism, lower CSF p-tau and t-tau, and better longitudinal cognitive performance, and were more likely to be taking medication for depression. In MCI only, florbetapir− participants had less hippocampal atrophy and hypometabolism and lower functional activity questionnaire scores compared to florbetapir+ participants. Conclusions: Overall, image analysis problems do not appear to be a primary explanation of amyloid negativity. Florbetapir− ADNI patients have a variety of clinical and biomarker features that differ from their florbetapir+ counterparts, suggesting that one or more non-AD etiologies (which may include vascular disease and depression) account for their AD-like phenotype. PMID:26968515

  10. Age-related iron deposition in the basal ganglia of controls and Alzheimer disease patients quantified using susceptibility weighted imaging.

    PubMed

    Wang, Dan; Li, Yan-Ying; Luo, Jian-Hua; Li, Yue-Hua

    2014-01-01

    This study aimed to investigate age-related iron deposition changes in healthy subjects and Alzheimer disease patients using susceptibility weighted imaging. The study recruited 182 people, including 143 healthy volunteers and 39 Alzheimer disease patients. All underwent conventional magnetic resonance imaging and susceptibility weighted imaging sequences. The groups were divided according to age. Phase images were used to investigate iron deposition in the bilateral head of the caudate nucleus, globus pallidus and putamen, and the angle radian value was calculated. We hypothesized that age-related iron deposition changes may be different between Alzheimer disease patients and controls of the same age, and that susceptibility weighted imaging would be a more sensitive method of iron deposition quantification. The results revealed that iron deposition in the globus pallidus increased with age, up to 40 years. In the head of the caudate nucleus, iron deposition peaked at 60 years. There was a general increasing trend with age in the putamen, up to 50-70 years old. There was significant difference between the control and Alzheimer disease groups in the bilateral globus pallidus in both the 60-70 and 70-80 year old group comparisons. In conclusion, iron deposition increased with age in the globus pallidus, the head of the caudate nucleus and putamen, reaching a plateau at different ages. Furthermore, comparisons between the control and Alzheimer disease group revealed that iron deposition changes were more easily detected in the globus pallidus.

  11. [Verbal and gestural communication in interpersonal interaction with Alzheimer's disease patients].

    PubMed

    Schiaratura, Loris Tamara; Di Pastena, Angela; Askevis-Leherpeux, Françoise; Clément, Sylvain

    2015-03-01

    Communication can be defined as a verbal and non verbal exchange of thoughts and emotions. While verbal communication deficit in Alzheimer's disease is well documented, very little is known about gestural communication, especially in interpersonal situations. This study examines the production of gestures and its relations with verbal aspects of communication. Three patients suffering from moderately severe Alzheimer's disease were compared to three healthy adults. Each one were given a series of pictures and asked to explain which one she preferred and why. The interpersonal interaction was video recorded. Analyses concerned verbal production (quantity and quality) and gestures. Gestures were either non representational (i.e., gestures of small amplitude punctuating speech or accentuating some parts of utterance) or representational (i.e., referring to the object of the speech). Representational gestures were coded as iconic (depicting of concrete aspects), metaphoric (depicting of abstract meaning) or deictic (pointing toward an object). In comparison with healthy participants, patients revealed a decrease in quantity and quality of speech. Nevertheless, their production of gestures was always present. This pattern is in line with the conception that gestures and speech depend on different communicational systems and look inconsistent with the assumption of a parallel dissolution of gesture and speech. Moreover, analyzing the articulation between verbal and gestural dimensions suggests that representational gestures may compensate for speech deficits. It underlines the importance for the role of gestures in maintaining interpersonal communication.

  12. Prevention of Alzheimer disease

    PubMed Central

    Scalco, Monica Zavaloni; van Reekum, Robert

    2006-01-01

    OBJECTIVE To review the evidence regarding prevention of Alzheimer disease (AD) in order to highlight the role of family medicine. QUALITY OF EVIDENCE Most of the evidence relating to prevention of AD is derived from observational (cross-sectional, case-control, or longitudinal) studies. Evidence from randomized controlled trials (RCTs) is available only for blood pressure control and for hormone replacement therapy for menopausal women. MAIN MESSAGE Many preventive approaches to AD have been identified, but no RCTs support their efficacy. Evidence from RCTs supports the effectiveness of blood pressure control in reducing incidence of AD, but demonstrates that postmenopausal women’s use of estrogen is ineffective in reducing it. Observational studies suggest that some preventive approaches, such as healthy lifestyle, ongoing education, regular physical activity, and cholesterol control, play a role in prevention of AD. These approaches can and should be used for every patient because they carry no significant risk. Currently, no effective pharmacologic interventions have been researched enough to support their use in prevention of AD. CONCLUSION Health professionals should educate patients, especially patients at higher risk of AD, about preventive strategies and potentially modifiable risk factors. PMID:16529393

  13. Reflections on Alzheimer's disease.

    PubMed

    Kushnir, S L

    1982-02-01

    As longevity increases, society will face a silent epidemic of idiopathic dementias. The concept, Alzheimer's disease, reflects a cumbersome and vaguely-defined cluster of signs, symptoms and other variables which might more appropriately be labelled as the idiopathic dementias, Alzheimer-type or IDAT. Diagnosis, which is made by exclusion and treatment, primarily custodial, demonstrates the complex nature and unfortunate prognosis of the problem. Dramatic progress, nevertheless, has been made in various scientific aspects of the issue, namely, in histology, genetics and neurochemistry. The resulting evidence warrants further speculation on the role of central cholinergic neurotransmission in cognitive functioning.

  14. Brain changes in Alzheimer's disease patients with implanted encapsulated cells releasing nerve growth factor.

    PubMed

    Ferreira, Daniel; Westman, Eric; Eyjolfsdottir, Helga; Almqvist, Per; Lind, Göran; Linderoth, Bengt; Seiger, Ake; Blennow, Kaj; Karami, Azadeh; Darreh-Shori, Taher; Wiberg, Maria; Simmons, Andrew; Wahlund, Lars-Olof; Wahlberg, Lars; Eriksdotter, Maria

    2015-01-01

    New therapies with disease-modifying effects are urgently needed for treating Alzheimer's disease (AD). Nerve growth factor (NGF) protein has demonstrated regenerative and neuroprotective effects on basal forebrain cholinergic neurons in animal studies. In addition, AD patients treated with NGF have previously shown improved cognition, EEG activity, nicotinic binding, and glucose metabolism. However, no study to date has analyzed brain atrophy in patients treated with NGF producing cells. In this study we present MRI results of the first clinical trial in patients with AD using encapsulated NGF biodelivery to the basal forebrain. Six AD patients received the treatment during twelve months. Patients were grouped as responders and non-responders according to their twelve-months change in MMSE. Normative values were created from 131 AD patients from ADNI, selecting 36 age- and MMSE-matched patients for interpreting the longitudinal changes in MMSE and brain atrophy. Results at baseline indicated that responders showed better clinical status and less pathological levels of cerebrospinal fluid (CSF) Aβ1-42. However, they showed more brain atrophy, and neuronal degeneration as evidenced by higher CSF levels of T-tau and neurofilaments. At follow-up, responders showed less brain shrinkage and better progression in the clinical variables and CSF biomarkers. Noteworthy, two responders showed less brain shrinkage than the normative ADNI group. These results together with previous evidence supports the idea that encapsulated biodelivery of NGF might have the potential to become a new treatment strategy for AD with both symptomatic and disease-modifying effects.

  15. Comparison of reading and spelling in patients with probable Alzheimer's disease.

    PubMed

    Glosser, G; Grugan, P; Friedman, R B

    1999-07-01

    Patients with probable Alzheimer's disease (AD) are reported to show mild, but reliable, difficulties reading aloud and spelling to dictation exception words, which have unusual or unpredictable correspondence between their spelling and pronunciation (e.g., touch). To understand the cognitive dysfunction responsible for these impairments, 21 patients and 27 age-and education-matched controls completed specially designed tests of single-word oral reading and spelling to dictation. AD patients performed slightly below controls on all tasks and showed mildly exaggerated regularity effects (i.e., the difference in response accuracy between words with regular spellings minus exception words) in reading and spelling. Qualitative analyses, however, did not demonstrate response patterns consistent with impairment in central lexical orthographic processing. The authors conclude that the mild alexia and agraphia in AD reflect semantic deficits and nonlinguistic impairments rather than a specific disturbance in lexical orthographic processing.

  16. Assessing the Impact and Social Perception of Self-Regulated Music Stimulation with Patients with Alzheimer's Disease

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; O'Reilly, Mark F.; Singh, Nirbhay N.; Sigafoos, Jeff; Grumo, Gianluca; Pinto, Katia; Stasolla, Fabrizio; Signorino, Mario; Groeneweg, Jop

    2013-01-01

    We assessed the impact and social rating of an active and a passive music condition implemented with six patients with Alzheimer's disease. In the active condition, the patients used a simple hand response and a microswitch to self-regulate music stimulation inputs. In the passive condition, music stimulation was automatically presented throughout…

  17. Modifications of platelet from Alzheimer disease patients: a possible relation between membrane properties and NO metabolites.

    PubMed

    Vignini, Arianna; Nanetti, Laura; Moroni, Cinzia; Tanase, Laura; Bartolini, Marco; Luzzi, Simona; Provinciali, Leandro; Mazzanti, Laura

    2007-07-01

    Alzheimer disease (AD) is a chronic neurodegenerative disorder characterised by a progressive loss of memory and cognitive functions. The formation of nitric oxide (NO), by astrocytes, has been suggested to contribute to the neurodegnerative process. Some studies have described the participation of different isoforms of NOS in the progression of AD. The present work was conducted in order to investigate the role played by NO and peroxynitrite in platelets from AD patients, the possible correlation with Na(+)/K(+)-ATPase activity and the intracellular Ca(2+) in the same group of patients as well as the expression of NOS isoenzymes and nitrotyrosine as markers of NO synthesis and reactive protein nitration. NO production was significantly elevated in the platelets from AD patients compared to controls as well as l-arginine/NO-dependent ONOO(-). Membrane Na(+)/K(+)-ATPase activity was significantly decreased in patients than in controls while intracellular Ca(2+) concentration shows an opposite trend. Platelet from AD patients showed a significantly increased 1-[4-(trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence anisotropy compared with controls. Western blot analysis using anti-iNOS and eNOS monoclonal antibodies demonstrated that both isoforms were detectable in cell lysates as well as nitrotyrosine more pronounced in the cell lysates from AD patients than controls. In conclusion, the increased expression and activity of nitrergic system may produce platelet membrane alteration or vice versa. These modifications may contribute further to the neurodegenerative process in AD because the abnormal function of Alzheimer platelets play a very important role in the pathogenesis of the disease.

  18. Enhanced levels of mitochondrial enzyme 17beta-hydroxysteroid dehydrogenase type 10 in patients with Alzheimer disease and multiple sclerosis.

    PubMed

    Kristofiková, Zdena; Bocková, Markéta; Hegnerová, Katerina; Bartos, Ales; Klaschka, Jan; Rícný, Jan; Rípová, Daniela; Homola, Jirí

    2009-10-01

    The multifunctional mitochondrial enzyme 17beta-hydroxysteroid dehydrogenase type 10 might play a role in the development of Alzheimer disease via its high-affinity binding to amyloid beta peptides and its neuronal over-expression. It is suggested that the cerebrospinal fluid levels of the enzyme, free or bound to amyloid beta peptides, are a potential specific biomarker of Alzheimer disease. However, mitochondrial dysfunction seems to play a role in many neurological diseases including multiple sclerosis. In this study, the specificity of changes in relation to the enzyme over-expression was evaluated using enzyme-linked immunosorbent and surface plasmon resonance sensors. The data indicated pronounced increases in the enzyme levels, specifically to 179% in multiple sclerosis and to 573% in Alzheimer disease when compared to the age-matched controls. Although the differences between both diseases were statistically significant, enzyme levels do not appear to be a highly specific biomarker of Alzheimer disease. On the other hand, enhancement in levels of the enzyme bound to amyloid beta peptides was only observed in people with Alzheimer disease, which suggests that the complex should be further considered as a possible biomarker. In patients with multiple sclerosis, our results are the first to demonstrate significant changes in enzyme expression and to suggest possible alterations in amyloid beta peptides.

  19. [Biomarkers in Alzheimer's disease].

    PubMed

    García-Ribas, G; López-Sendón Moreno, J L; García-Caldentey, J

    2014-04-01

    The new diagnostic criteria for Alzheimer's disease (AD) include brain imaging and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the certainty of whether a patient has an ongoing AD neuropathologic process or not. Three CSF biomarkers, Aß42, total tau, and phosphorylated tau, reflect the core pathological features of AD. It is already known that these pathological processes of AD starts decades before the first symptoms, so these biomarkers may provide means of early disease detection. At least three stages of AD could be identified: preclinical AD, mild cognitive impairment due to AD, and dementia due to AD. In this review, we aim to summarize the CSF biomarker data available for each of these stages. We also review the actual research on blood-based biomarkers. Recent studies on healthy elderly subjects and on carriers of dominantly inherited AD mutations have also found biomarker changes that allow separate groups in these preclinical stages. These studies may aid for segregate populations in clinical trials and objectively evaluate if there are changes over the pathological processes of AD. Limits to widespread use of CSF biomarkers, apart from the invasive nature of the process itself, is the higher coefficient of variation for the analyses between centres. It requires strict pre-analytical and analytical procedures that may make feasible multi-centre studies and global cut-off points for the different stages of AD.

  20. Alternative Medicine and Alzheimer's Disease

    PubMed Central

    Kelley, Brendan J.; Knopman, David S.

    2009-01-01

    Background Alternative medicine has an extensive worldwide history and is commonly used by older patients. A number of different alternative medicines are used by patients having Alzheimer's disease. It is both desirable and expected for clinicians to be acquainted with these medications. Review Summary This paper discusses the available clinical trial evidence regarding eight agents commonly used by people having Alzheimer's disease. We provide an overview of the history and basic scientific evidence available for each agent, followed by a critical analysis of the evidence available from clinical trials, including the number of participants, trial duration and specific outcomes evaluated. Conclusion While many of these compounds have been associated with interesting basic science, none has shown clear clinical benefit to date. Data available for some, such as ginkgo biloba, curcumin and huperzine A, suggest that further evaluation is warranted. Familiarity with this literature will allow clinicians to provide meaningful recommendations to patients who wish to use these agents. PMID:18784599

  1. Blood transcriptomic biomarkers of Alzheimer's disease patients treated with EHT 0202.

    PubMed

    Désiré, Laurent; Blondiaux, Elodie; Carrière, Jennifer; Haddad, Raphael; Sol, Olivier; Fehlbaum-Beurdeley, Pascale; Einstein, Rich; Zhou, Weiyin; Pando, Matthew P

    2013-01-01

    Monitoring the genomic expression of patients in clinical trials for Alzheimer's disease (AD) can assist trial design and treatment response analysis. Here, we report on the identification in AD patients of blood-based transcriptomic signatures associated with treatment response of EHT 0202, a new compound with potential disease-modifying and symptomatic properties, in a 3-month, placebo-controlled, Phase IIA study aimed at determining the clinical safety, tolerability, and exploratory efficacy of EHT 0202 (40 and 80 mg bid) as adjunctive therapy to one cholinesterase inhibitor in mild to moderate AD patients. Genome-wide transcriptomic profiling was performed on blood samples taken prior to treatment and at study completion in a subpopulation of 60 AD patients selected as either the 10 worst disease decliners or the 10 best improvers of each treatment group, using ADAS-Cog scores as measure of disease severity. In the patients responding to EHT 0202, a pre-treatment (baseline) transcriptomic signature showed activation of pathways related to AD, CNS disorders, diabetes, inflammation, and autoimmunity, while a post-treatment signature indicated reduced activation of these pathways with induced metabolic and transcription stimulation. This pilot study demonstrates the utility of blood transcriptomic signatures used as biomarkers for predicting patient response or monitoring efficacy, for an administered therapeutic drug in a complex disease such as AD. For EHT 0202 or other AD drugs, such biomarkers may help to improve strategies to better identify appropriate patient populations for treatment, understand the drug mechanism of efficacy, and/or clarify the inherent subjectivity in most clinical endpoints used in this disease.

  2. Oxidative Stress in Patients with Alzheimer's Disease: Effect of Extracts of Fermented Papaya Powder

    PubMed Central

    Barbagallo, Mario; Marotta, Francesco; Dominguez, Ligia J.

    2015-01-01

    Brain tissue is particularly susceptible to oxidative stress (OS). Increased production of reactive oxygen species (ROS), reduced antioxidant systems, and decreased efficiency in repairing mechanisms have been linked to Alzheimer's disease (AD). Postmortem studies in AD patients' brains have shown oxidative damage markers (i.e., lipid peroxidation, protein oxidative damage, and glycoxidation). Fermented papaya (FPP, a product of Carica papaya Linn fermentation with yeast) is a nutraceutical supplement with favorable effects on immunological, hematological, inflammatory, and OS parameters in chronic/degenerative diseases. We studied 40 patients (age 78.2 ± 1.1 years), 28 AD patients, and 12 controls. Urinary 8-OHdG was measured to assess OS. Twenty AD patients were supplemented with FPP (Immunage, 4.5 grams/day) for 6 months, while controls did not receive any treatment. At baseline, 8-OHdG was significantly higher in patients with AD versus controls (13.7 ± 1.61 ng/mL versus 1.6 ± 0.12 ng/mL, P < 0.01). In AD patients FPP significantly decreased 8-OHdG (14.1 ± 1.7 ng/mL to 8.45 ± 1.1 ng/mL, P < 0.01), with no significant changes in controls. AD is associated with increased OS, and FPP may be helpful to counteract excessive ROS in AD patients. PMID:25944987

  3. Assessment of Health-Related Quality of Life for Caregivers of Alzheimer's Disease Patients

    PubMed Central

    Papadopoulos, Angelos A.; Panagiotakos, Demosthenes B.

    2016-01-01

    Background. Alzheimer's disease (AD) dementia is a chronic neurodegenerative disorder that results in total cognitive impairment and functional decline. Family members are the most usual caregivers worldwide, resulting in a subsequent degradation of their quality of life. Methods. During November 2013–March 2014 in Athens, Greece, 155 AD patients' family caregivers' Health-Related Quality of Life and existence of depressive symptomatology were assessed. Results. A strong negative correlation between the dimensions of HRQoL and the scores of the depression scale was revealed. AD patients' caregivers have a lower HRQoL almost in all dimensions compared to the Greek urban general population. The caregivers' social role, the existence of emotional problems, and their mental health status led to this result. Furthermore significantly important differences in caregivers' total HRQoL and depressive symptomatology were indicated in relation to their gender, hypertension existence, patient care frequency, cohabitation with the patient, disease aggravation, and economic status. Conclusions. Caring for relatives with AD strongly correlates with negative caregivers' HRQoL scores and adversely affects their depressive symptomatology. This negative correlation is enhanced in the later stages of the disease, in greater frequency of care, through living with a patient, in poor financial status, and with the existence of a chronic illness. PMID:28083154

  4. MR diffusion tensor imaging (DTI) and neuropsychological testing for neuronal connectivity in Alzheimer's disease (AD) patients

    NASA Astrophysics Data System (ADS)

    Zhong, Jianhui; Ni, Hongyan; Zhu, Tong; Ekholm, Sven; Kavcic, Voyko

    2004-04-01

    We have used MR DTI to identify relevant brain structures involved in visuospatial processing, in an attempt to link perceptual and attentional impairments to WM changes in Alzheimer's disease (AD) patients. Correlation of DTI measured parameters with results of several neuropsychological tests will be reported here. Several issues related to quantitation of DTI parameters in ROI analysis are addressed. In spite of only a small number of subjects were studied so far, we found not only that AD patients showed significant decrease of white matter (WM) integrity in corpus callosum (CC), most prominent at the posterior portion, but also found significant correlations between the DTI parameters and scores from several neuropsychological tests. Our preliminary results suggest that DTI help to improve the overall accuracy rate in distinguishing between early AD onset and age-related functional decline, and potentially may improve efficiency in differentiating between different types of dementia.

  5. Vibrational spectroscopic analysis of peripheral blood plasma of patients with Alzheimer's disease.

    PubMed

    Carmona, Pedro; Molina, Marina; López-Tobar, Eduardo; Toledano, Adolfo

    2015-10-01

    Using Raman and infrared spectroscopy, we monitored spectral changes occurring in the blood plasma of patients with Alzheimer's disease (AD) in relation to healthy controls. The protein secondary structure as reflected by amide I band involves β-sheet enrichment, which may be attributable to Aβ peptide formation and to increasing proportion of the globulins that are β-sheet rich. Likewise, the behavior of the infrared 1200-1000-cm(-1) region and the Raman 980-910- and 450-400-cm(-1) regions can be explained in terms of the said plasma composition change. Further, the 744-cm(-1) Raman band from healthy control plasma shows frequency upshifting in the course of AD, which may be generated by the platelets collected in blood plasma. Linear discrimination analysis and receiver operating characteristic (ROC) analysis have been used to distinguish between patients with AD and age-matched healthy controls with a diagnostic accuracy of about 94%.

  6. Patient Mood and Instrumental Activities of Daily Living in Alzheimer Disease: Relationship Between Patient and Caregiver Reports.

    PubMed

    Votruba, Kristen L; Persad, Carol; Giordani, Bruno

    2015-09-01

    This retrospective study investigated the relationship between self-reports and caregiver perceptions of patients' depressive symptoms and the respective ability of these reports to predict instrumental activities of daily living (IADLs) beyond what is accounted for by cognitive abilities in 71 patients with mild Alzheimer disease. Patients completed the Geriatric Depression Scale-Short Form, and caregivers completed the Behavior Rating Scale for Dementia assessing their perception of patients' depressive symptoms. Caregivers also completed IADL items from the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory. Cognitive measures included the Mini-Mental State Examination, Logical Memory from the Wechsler Memory Scale III, and Trail Making Test, Part B. The relationship between self-reported depressive symptoms and caregiver report of patients' depressive symptoms showed a trend toward significance (r = .22, P = .06). Measures of depressive symptoms significantly predicted 12.5% of the variance in IADLs performance, beyond that accounted for by patient demographics and cognitive functioning. Interestingly, patients' reports, rather than caregivers', were particularly useful in this prediction.

  7. Healing gardens and cognitive behavioral units in the management of Alzheimer's disease patients: the Nancy experience.

    PubMed

    Rivasseau Jonveaux, Therese; Batt, Martine; Fescharek, Reinhard; Benetos, Athanase; Trognon, Alain; Bah Chuzeville, Stanislas; Pop, Alina; Jacob, Christel; Yzoard, Manon; Demarche, Laetitia; Soulon, Laure; Malerba, Gabriel; Bouvel, Bruno

    2013-01-01

    The French Alzheimer Plan 2008-2012 anticipates the implementation of new Units specialized in cognitive rehabilitation and psycho-behavioral therapy of Alzheimer's disease (AD) patients. Conceived for AD and other dementia patients of all ages, their objectives are to propose a cognitive rehabilitation program, to prevent or treat psycho-behavioral crises, and to provide support and educational therapy to the family and professional caregivers, in order to ease the patient's return to his or her previous way of life. Studies on green spaces and healing gardens in health-care settings have revealed objective and measurable improvements in the patient's well-being. The Plan officially stipulates for the first time the need to make healing gardens an integral part of these Units, but it does not provide specific recommendations or criteria for implementing such gardens. Although green spaces and gardens are available in many French Care Units, they are rarely specifically adapted to the needs of AD patients. In Nancy, the Art, Memory and Life garden, a specific concept guided by a neuropsychological approach, was developed and complemented by an artistic vision based on cultural invariants. The main objective of this article is to describe the various steps of the process that led to the creation of this garden: the collection of experiences and information by a pilot group, surveys of patients, visitors, and caregivers before and after establishment of the garden, and implementation of a multi-professional group project. The specifications, the organizational criteria, the therapeutic project, and the criteria for the conception of such a garden stemming from our clinical experience with the Art, Memory and Life garden in Nancy, are described herein. We also present the first assessment following the implementation of the project.

  8. Dopamine differently modulates central cholinergic circuits in patients with Alzheimer disease and CADASIL.

    PubMed

    Nardone, Raffaele; Höller, Yvonne; Thomschewski, Aljosha; Kunz, Alexander Baden; Lochner, Piergiorgio; Golaszewski, Stefan; Trinka, Eugen; Brigo, Francesco

    2014-10-01

    Short-latency afferent inhibition (SAI) technique gives the opportunity to non-invasively test an inhibitory circuit in the human cerebral motor cortex that depends mainly on central cholinergic activity. Important SAI abnormalities have been reported in both patients with Alzheimer disease (AD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a model of "pure" vascular dementia (VD). Interestingly, a normalization of SAI was observed in AD after levo-dopa (L-dopa) administration. We aimed to determine whether the pharmacological manipulation of the dopaminergic system can also interfere with SAI test in CADASIL patients, compared with AD patients and healthy controls. SAI was found to be significantly reduced in both patient groups. L-Dopa significantly increased SAI in the AD patients, while it failed to restore SAI abnormality in CADASIL patients. Therefore, L-dopa-mediated changes on SAI in AD patients seem to be a specific effect. The present study supports the notion that relationship between acetylcholine and dopamine systems may be specifically abnormal in AD. L-Dopa challenge may thus be able to differentiate the patients with AD or a mixed form of dementia from those with "pure" VD.

  9. Preserved conceptual implicit memory for pictures in patients with Alzheimer's disease.

    PubMed

    Deason, Rebecca G; Hussey, Erin P; Flannery, Sean; Ally, Brandon A

    2015-10-01

    The current study examined different aspects of conceptual implicit memory in patients with mild Alzheimer's disease (AD). Specifically, we were interested in whether priming of distinctive conceptual features versus general semantic information related to pictures and words would differ for the mild AD patients and healthy older adults. In this study, 14 healthy older adults and 15 patients with mild AD studied both pictures and words followed by an implicit test section, where they were asked about distinctive conceptual or general semantic information related to the items they had previously studied (or novel items). Healthy older adults and patients with mild AD showed both conceptual priming and the picture superiority effect, but the AD patients only showed these effects for the questions focused on the distinctive conceptual information. We found that patients with mild AD showed intact conceptual picture priming in a task that required generating a response (answer) from a cue (question) for cues that focused on distinctive conceptual information. This experiment has helped improve our understanding of both the picture superiority effect and conceptual implicit memory in patients with mild AD in that these findings support the notion that conceptual implicit memory might potentially help to drive familiarity-based recognition in the face of impaired recollection in patients with mild AD.

  10. Immunotherapy for Alzheimer's Disease

    PubMed Central

    Wisniewski, Thomas; Goni, Fernando

    2014-01-01

    Alzheimer's disease (AD) is the most common cause of dementia worldwide. In AD the normal soluble amyloid β (sAβ) peptide is converted into oligomeric/fibrillar Aβ. The oligomeric forms of Aβ are thought to be the most toxic, while fibrillar Aβ becomes deposited as amyloid plaques and congophilic angiopathy, which serve as neuropathological markers of the disease. In addition the accumulation of abnormally phosphorylated tau as soluble toxic oligomers and as neurofibrillary tangles is a critical part of the pathology. Numerous therapeutic interventions are under investigation to prevent and treat AD. Among the more exciting and advanced of these approaches is vaccination. Active and passive Immunotherapy targeting only Aβ has been successful in many AD model animal trials; however, the more limited human data has shown much less benefit so far, with encephalitis occurring in a minority of patients treated with active immunization and vasogenic edema or amyloid-related imaging abnormalities (ARIA) being a complication in some passive immunization trials. Therapeutic intervention targeting only tau has been tested only in mouse models; and no approaches targeting both pathologies concurrently has been attempted, until very recently. The immune approaches tried so far were targeting a self-protein, albeit in an abnormal conformation; however, effective enhanced clearance of the disease associated conformer has to be balanced with the potential risk of stimulating excessive toxic inflammation. The design of future more effective immunomodulatory approaches will need to target all aspects of AD pathology, as well as specifically targeting pathological oligomeric conformers, without the use of any self-antigen. PMID:24412277

  11. [Calcium hypothesis of Alzheimer disease].

    PubMed

    Riazantseva, M A; Mozhaeva, G N; Kaznacheeva, E V

    2012-01-01

    Alzheimer's disease is the most common neurodegenerative disorder characterized by progressive memory and cognitive abilities loss. The etiology of Alzheimer's disease is poorly understood. In this regard, there is no effective treatment for the disease. Various hypotheses to explain the nature of the pathology of Alzheimer's disease led to the development of appropriate therapeutics. Despite of decades of research and clinical trials available therapeutics, at best, can only slow down the progression of the disease, but cannot cure it. This review dedicated to the one of modern hypotheses of Alzheimer's disease pathogenesis implied the impairment of calcium homeostasis as a key event for the development of neurodegenerative processes.

  12. Amyloid imaging in prodromal Alzheimer's disease

    PubMed Central

    2011-01-01

    Patients with mild cognitive impairment are at an increased risk of progression to Alzheimer's disease. However, not all patients with mild cognitive impairment progress, and it is difficult to accurately identify those patients who are in the prodromal stage of Alzheimer's disease. In a recent paper, Koivunen and colleagues report that Pittsburgh compound-B, an amyloid-beta positron emission tomography ligand, predicts the progression of patients with mild cognitive impairment to Alzheimer's disease. Of 29 subjects with mild cognitive impairment, 21 (72%) had a positive Pittsburgh compound-B positron emission tomography baseline scan. In their study, 15 of these 21 (71%) patients progressed to Alzheimer's disease, whilst only 1 out of 8 (12.5%) Pittsburgh compound-B-negative patients with mild cognitive impairment did so. Moreover, in these mild cognitive impairment patients, the overall amyloid burden increased approximately 2.5% during the follow-up period. This is consistent with other longitudinal amyloid imaging studies that found a similar increase in amyloid deposition over time in patients with mild cognitive impairment. These studies together challenge current theories that propose a flattening of the increase of brain amyloid deposition already in the preclinical stage of Alzheimer's disease. These findings may have important implications for the design of future clinical trials aimed at preventing progression to Alzheimer's disease by lowering the brain amyloid-beta burden in patients with mild cognitive impairment. PMID:21936965

  13. Applicability of the abbreviated neuropsychologic battery (NEUROPSI) in Alzheimer disease patients.

    PubMed

    Abrisqueta-Gomez, Jacqueline; Ostrosky-Solis, Feggy; Bertolucci, Paulo H F; Bueno, Orlando F A

    2008-01-01

    NEUROPSI is a brief neuropsychologic battery developed to briefly assess a wide spectrum of cognitive functions. The aim of this study was to examine the applicability of a Portuguese version of this battery and verify the efficacy in detecting cognitive impairment in Alzheimer disease (AD) patients. NEUROPSI was applied to 75 elderly people, 25 patients with probable AD in mild stage (AD1), 25 patients in moderate stage (AD2), and 25 healthy elderly persons (control group), matched with the AD patients for age and schooling. Before testing all participants were applied the Mini-Mental State Examination. Results showed significant differences in total scores of the tests; NEUROPSI (P<0.001) and Mini-Mental State Examination (P<0.001), and the control group scored highest in both of the tests followed by groups AD1 and AD2. Differences were also found between the initial phase and the moderate phase. Results indicate that NEUROPSI is an efficient instrument for detecting AD patients in the initial stage of the disease.

  14. Decline of human tactile angle discrimination in patients with mild cognitive impairment and Alzheimer's disease.

    PubMed

    Yang, Jiajia; Ogasa, Takashi; Ohta, Yasuyuki; Abe, Koji; Wu, Jinglong

    2010-01-01

    There is a need to differentiate between patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) from normal-aged controls (NC) in the field of clinical drug discovery. In this study, we developed a tactile angle discrimination system and examined whether the ability to discriminate tactile angle differed between patients with MCI and AD and the NC group. Thirty-seven subjects were divided into three groups: NC individuals (n=14); MCI patients (n=10); and probable AD patients (n=13). All subjects were asked to differentiate the relative sizes of the reference angle (60°) and one of eight comparison angles by passive touch. The accuracy of angle discrimination was measured and the discrimination threshold was calculated. We discovered that there were significant differences in the angle discrimination thresholds of AD patients compared to the NC group. Interestingly, we also found that ability to discriminate tactile angle of MCI patients were significantly lower than that of the NC group. This is the first study to report that patients with MCI and AD have substantial performance deficits in tactile angle discrimination compared to the NC individuals. This finding may provide a monitor and therapeutic approach in AD diagnosis and treatment.

  15. Predictive Factors of Rapid Cognitive Decline in Patients with Alzheimer Disease

    PubMed Central

    Barbe, Coralie; Morrone, Isabella; Novella, J.L.; Dramé, Moustapha; Wolak-Thierry, Aurore; Aquino, Jean-Pierre; Ankri, Joël; Jolly, Damien; Mahmoudi, Rachid

    2016-01-01

    Aim To determine predictive factors associated with rapid cognitive decline (RCD) in elderly patients suffering from Alzheimer disease (AD). Methods Patients suffering from mild to moderate AD were included. RCD was defined as the loss of at least 3 points on the Mini-Mental State Examination (MMSE) over 12 months. Factors associated with RCD were identified by logistic regression. Results Among 123 patients included, 61 were followed up until 12 months. RCD occurred in 46% of patients (n = 28). Polymedication (p < 0.0001), the fact that the caregiver was the child or spouse of the patient (p < 0.0001) and autonomy for washing (p < 0.0001) were protective factors against RCD, while the presence of caregiver burden (p < 0.0001) was shown to be a risk factor for RCD. Conclusion Early detection of the RCD risk in AD patients could make it possible to anticipate the patient's medical needs and adjust the care plan for caregiver burden. PMID:28101101

  16. A genetic screen of the mutations in the Korean patients with early-onset Alzheimer's disease.

    PubMed

    An, Seong Soo; Park, Sun Ah; Bagyinszky, Eva; Bae, Sun Oh; Kim, Yoon-Jeong; Im, Ji Young; Park, Kyung Won; Park, Kee Hyung; Kim, Eun-Joo; Jeong, Jee Hyang; Kim, Jong Hun; Han, Hyun Jeong; Choi, Seong Hye; Kim, SangYun

    2016-01-01

    Early-onset Alzheimer's disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer's disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer's disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16-17), PSEN1 (exons 3-12), and PSEN2 (exons 3-12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be excluded. We

  17. What do Alzheimer's disease patients know about animals? It depends on task structure and presentation format.

    PubMed

    Rich, Jill B; Park, Norman W; Dopkins, Stephen; Brandt, Jason

    2002-01-01

    Deficits on tasks requiring semantic memory in Alzheimer's disease (AD) may be due to storage loss, a retrieval deficit, or both. To address this question, we administered multiple tasks involving 9 exemplars of the category "animals," presented as both words and pictures, to 12 AD patients and 12 nondemented individuals. Participants made semantic judgments by class (sorting task), similarity (triadic comparison task), and dimensional attributes (ordering task). Relative to control participants, AD patients were impaired on an unstructured sorting task, but did not differ on a constrained sorting task. On the triadic comparison task, the patients were as likely to make judgments based on size as domesticity attributes, whereas control participants made judgments based primarily on domesticity. The patients' judgments were also less consistent across tasks than those of control participants. On the ordering tasks, performance was generally comparable between groups with pictures but not words, suggesting that pictures enable AD patients to access information from semantic memory that is less accessible with lexical stimuli. These results suggest that AD patients' semantic judgments are impaired when the retrieval context is unstructured, but perform normally under supportive retrieval conditions.

  18. Pharmacological modulation of cognitive and behavioral symptoms in patients with dementia due to Alzheimer's disease.

    PubMed

    de Oliveira, Fabricio Ferreira; Bertolucci, Paulo Henrique Ferreira; Chen, Elizabeth Suchi; Smith, Marilia de Arruda Cardoso

    2014-01-15

    To evaluate correlations of pharmacological treatment with cognitive and behavioral symptoms in patients with dementia due to Alzheimer's disease with low schooling, subjects were assessed for demographic features, neuropsychiatric symptoms, cognitive decline, functionality, caregiver burden, APOE haplotypes and pharmacological treatment. Among 217 patients, use of cholinesterase inhibitors with or without Memantine was associated with less neuropsychiatric symptoms, while anti-psychotics and/or anti-epileptic drugs were associated with lower instrumental functionality. Anti-psychotics were also associated with more neuropsychiatric symptoms in moderately impaired patients, possibly reflecting the greater need for such treatment when behavioral symptoms are present. Patients receiving more medications were usually younger, obese, married, with higher schooling and more neuropsychiatric symptoms. APOE4+ haplotypes were correlated with earlier dementia onset, but not with pharmacological treatment. Higher caregiver burden was associated with more psychotropic drugs. A trend was found for treatment with cholinesterase inhibitors and Memantine to be associated with longer lengths of dementia for moderately impaired but not for severely impaired patients, regardless of APOE haplotypes, translating into a synergistic effect among such medications for slowing cognitive decline but not for prolonging survival. Further longitudinal studies may be required to assess dose-response relationships regarding treatment with psychotropics for patients with dementia.

  19. Disrupted Network Topology in Patients with Stable and Progressive Mild Cognitive Impairment and Alzheimer's Disease

    PubMed Central

    Pereira, Joana B.; Mijalkov, Mite; Kakaei, Ehsan; Mecocci, Patricia; Vellas, Bruno; Tsolaki, Magda; Kłoszewska, Iwona; Soininen, Hilka; Spenger, Christian; Lovestone, Simmon; Simmons, Andrew; Wahlund, Lars-Olof; Volpe, Giovanni; Westman, Eric

    2016-01-01

    Recent findings suggest that Alzheimer's disease (AD) is a disconnection syndrome characterized by abnormalities in large-scale networks. However, the alterations that occur in network topology during the prodromal stages of AD, particularly in patients with stable mild cognitive impairment (MCI) and those that show a slow or faster progression to dementia, are still poorly understood. In this study, we used graph theory to assess the organization of structural MRI networks in stable MCI (sMCI) subjects, late MCI converters (lMCIc), early MCI converters (eMCIc), and AD patients from 2 large multicenter cohorts: ADNI and AddNeuroMed. Our findings showed an abnormal global network organization in all patient groups, as reflected by an increased path length, reduced transitivity, and increased modularity compared with controls. In addition, lMCIc, eMCIc, and AD patients showed a decreased path length and mean clustering compared with the sMCI group. At the local level, there were nodal clustering decreases mostly in AD patients, while the nodal closeness centrality detected abnormalities across all patient groups, showing overlapping changes in the hippocampi and amygdala and nonoverlapping changes in parietal, entorhinal, and orbitofrontal regions. These findings suggest that the prodromal and clinical stages of AD are associated with an abnormal network topology. PMID:27178195

  20. Effects of Diabetes Mellitus on Cognitive Decline in Patients with Alzheimer Disease: A Systematic Review.

    PubMed

    Li, Jun; Cesari, Matteo; Liu, Fei; Dong, Birong; Vellas, Bruno

    2017-02-01

    Basic and clinical research support a link between diabetes mellitus and Alzheimer disease (AD). However, the relationship with AD progression is unclear. This review focuses on the association between diabetes and cognitive decline in patients with AD. The literature published through May 2015 was searched in 3 databases: PubMed, Embase and Cochrane. Studies evaluating the effects of diabetes on patients with AD or cognitive decline were included, and extracted data were analyzed. A total of 10 articles met the inclusion criteria for review. The results of these studies were inconsistent in terms of the association between diabetes and cognitive decline. Only 2 studies demonstrated that the presence of diabetes was independently related to the progression of cognitive decline in the patients with AD, and 3 studies suggested that histories of diabetes were not correlated with the changes in cognitive function in patients with AD. Half of the included studies even indicated that histories of diabetes were associated with lesser declines in cognitive function in patients with AD. Current evidence indicates that the link between diabetes and cognitive decline in patients with AD is uncertain. Further clinical studies are needed, with larger samples, long-term follow up and an extended battery of cognitive assessments.

  1. Serum calreticulin is a negative biomarker in patients with Alzheimer's disease.

    PubMed

    Lin, Qiao; Cao, Yunpeng; Gao, Jie

    2014-11-25

    Calreticulin is down-regulated in the cortical neurons of patients with Alzheimer's disease (AD) and may be a potential biomarker for the diagnosis of AD. A total of 128 AD patients were randomly recruited from May 2012 to July 2013. The mRNA levels of calreticulin were measured from the serum of tested subjects using real-time quantitative reverse transcriptase-PCR (real-time qRT-PCR). Serum levels of calreticulin were determined by ELISA and Western Blot. Serum levels of calreticulin in AD patients were significantly lower than those from a healthy group (p < 0.01). The baseline characters indicated that sample size, gender, mean age, diabetes and BMI (body mass index) were not major sources of heterogeneity. The serum levels of mRNA and protein of calreticulin were lower in AD patients than those from a healthy group, and negatively associated with the progression of AD according to CDR scores (p < 0.01). Thus, there is a trend toward decreased serum levels of calreticulin in the patients with progression of AD. Serum levels of calreticulin can be a negative biomarker for the diagnosis of AD patients.

  2. Screening for Patients with Mild Alzheimer Disease Using Frequency Doubling Technology Perimetry

    PubMed Central

    Aykan, Umit; Akdemir, M. Orcun; Yildirim, Ozlem; Varlibas, Figen

    2013-01-01

    Abstract We compared the visual field performances of patients with mild Alzheimer disease (AD) with normal subjects and detected visual field impairment attributable to the magnocellular pathway using frequency doubling technology—Matrix (FDT-Matrix). We recruited 43 patients with mild AD (mean age: 68.0 ± 7.2 years) and 33 controls who are visually and cognitively normal (mean age: 64.1 ± 6.4 years). All participants had at least two reliable FDT-Matrix 30-2 tests. Reliability indices, global indices (mean deviation and pattern standard deviation), and glaucoma hemifield test results were measured with FDT-Matrix. The mean test duration was significantly longer in patient group compared with controls (p = 0.002). Among the reliability indices, false negatives were higher in patient group than controls (p = 0.003). There were statistically significant differences in mean deviation and pattern standard deviation values (p < 0.0001 and p < 0.0001, respectively) and glaucoma hemifield test results (p < 0.001) between the patient and the control group. Our results imply that the pathogenesis of cognitive deterioration may not only be confined to the cortical area but also to the magnocellular pathway. We underline that FDT testing can be useful for the identification of early impairment and the follow-up of patients with AD. PMID:28167993

  3. Cerebrospinal fluid substance P concentrations are elevated in patients with Alzheimer's disease.

    PubMed

    Johansson, Per; Almqvist, Erik G; Wallin, Anders; Johansson, Jan-Ove; Andreasson, Ulf; Blennow, Kaj; Zetterberg, Henrik; Svensson, Johan

    2015-11-16

    The neuropeptides substance P, orexin A (hypocretin-1) and neurotensin are signaling molecules that influence brain activity. We examined their cerebrospinal fluid (CSF) levels in a study population consisting of Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n=32), stable MCI (SMCI, n=13), other dementias (n=15), and healthy controls (n=20). CSF substance P level was increased in AD patients compared to patients with other dementias and healthy controls (P<0.05 and P<0.01, respectively). Patients with other dementia or SMCI had lower CSF orexin A level than AD patients (both P<0.05) and marginally lower level than healthy controls (both P=0.05). CSF neurotensin level was similar in all groups. In the total study population (n=80), CSF substance P level correlated positively with CSF levels of T-tau and P-tau, and in AD patients (n=32), CSF substance P level correlated positively with CSF Aβ1-42 level. In conclusion, CSF substance P level was elevated in AD patients and correlated with CSF Aβ1-42 level, a well established marker of senile plaque pathology. The role of low CSF orexin A level in other dementias or SMCI needs to be explored in further studies.

  4. Changes in cognitive domains during three years in patients with Alzheimer's disease treated with donepezil

    PubMed Central

    Persson, Cecilia M; Wallin, Åsa K; Levander, Sten; Minthon, Lennart

    2009-01-01

    Background The objective was to identify separate cognitive domains in the standard assessment tools (MMSE, ADAS-Cog) and analyze the process of decline within domains during three years in Alzheimer's disease (AD) patients with donepezil treatment. Method AD patients (n = 421) were recruited from a clinical multi-centre study program in Sweden. Patients were assessed every six months during three years. All patients received donepezil starting directly after study entry. After dropouts, 158 patients remained for analyses over three years. Data for the other patients were analysed until they dropped out (4 groups based on length in study). Results Factor analyses of all items suggested that there were three intercorrelated factors: a General, a Memory and a Spatial factor for which we constructed corresponding domains. Overall there was a cognitive improvement at six months followed by a linear drop over time for the three domains. Some group and domain differences were identified. Patients who remained longer in the study had better initial performance and a slower deterioration rate. The early dropouts showed no improvement at six months and many dropped out due to side effects. The other groups displayed a performance improvement at six months that was less pronounced in the Memory domain. Before dropping out, deterioration accelerated, particularly in the Spatial domain. Conclusion The course of illness in the three domains was heterogeneous among the patients. We were not able to identify any clinically relevant correlates of this heterogeneity. As an aid we constructed three algorithms corresponding to the cognitive domains, which can be used to characterize patients initially, identify rapid decliners and follow the course of the disease. PMID:19208247

  5. Moderate Changes in the Circadian System of Alzheimer's Disease Patients Detected in Their Home Environment

    PubMed Central

    Weissová, Kamila; Bartoš, Aleš; Sládek, Martin; Nováková, Marta; Sumová, Alena

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative disease often accompanied with disruption of sleep-wake cycle. The sleep-wake cycle is controlled by mechanisms involving internal timekeeping (circadian) regulation. The aim of our present pilot study was to assess the circadian system in patients with mild form of AD in their home environment. In the study, 13 elderly AD patients and 13 age-matched healthy control subjects (the patient's spouses) were enrolled. Sleep was recorded for 21 days by sleep diaries in all participants and checked by actigraphy in 4 of the AD patient/control couples. The samples of saliva and buccal mucosa were collected every 4 hours during the same 24 h-interval to detect melatonin and clock gene (PER1 and BMAL1) mRNA levels, respectively. The AD patients exhibited significantly longer inactivity interval during the 24 h and significantly higher number of daytime naps than controls. Daily profiles of melatonin levels exhibited circadian rhythms in both groups. Compared with controls, decline in amplitude of the melatonin rhythm in AD patients was not significant, however, in AD patients more melatonin profiles were dampened or had atypical waveforms. The clock genes PER1 and BMAL1 were expressed rhythmically with high amplitudes in both groups and no significant differences in phases between both groups were detected. Our results suggest moderate differences in functional state of the circadian system in patients with mild form of AD compared with healthy controls which are present in conditions of their home dwelling. PMID:26727258

  6. A computer-aided program for helping patients with moderate Alzheimer's disease engage in verbal reminiscence.

    PubMed

    Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Ferlisi, Gabriele; Zullo, Valeria; Schirone, Simona; Prisco, Raffaella; Denitto, Floriana

    2014-11-01

    This study assessed a simple computer-aided program for helping patients with moderate Alzheimer's disease engage in verbal reminiscence. In practice, the program was aimed at fostering the patient's verbal engagement on a number of life experiences/topics previously selected for him or her and introduced in the sessions through a friendly female, who appeared on the computer screen. The female asked the patient about the aforementioned experiences/topics, and provided him or her with positive attention, and possibly verbal guidance (i.e., prompts/encouragements). Eight patients were involved in the study, which was carried out according to non-concurrent multiple baseline designs across participants. Seven of them showed clear improvement during the intervention phase (i.e., with the program). Their mean percentages of intervals with verbal engagement/reminiscence ranged from close to zero to about 15 during the baseline and from above 50 to above 75 during the intervention. The results were discussed in relation to previous literature on reminiscence therapy, with specific emphasis on the need for (a) replication studies and (b) the development of new versions of the technology-aided program to improve its impact and reach a wider number of patients.

  7. Direct visualization of fungal infection in brains from patients with Alzheimer's disease.

    PubMed

    Pisa, Diana; Alonso, Ruth; Juarranz, Angeles; Rábano, Alberto; Carrasco, Luis

    2015-01-01

    Recently, we have reported the presence of fungal infections in patients with Alzheimer's disease (AD). Accordingly, fungal proteins and DNA were found in brain samples, demonstrating the existence of infection in the central nervous system. In the present work, we raised antibodies to specific fungal species and performed immunohistochemistry to directly visualize fungal components inside neurons from AD patients. Mice infected with Candida glabrata were initially used to assess whether yeast can be internalized in mammalian tissues. Using polyclonal rabbit antibodies against C. glabrata, rounded immunopositive cells could be detected in the cytoplasm of cells from liver, spleen, and brain samples in infected, but not uninfected, mice. Immunohistochemical analyses of tissue from the frontal cortex of AD patients revealed the presence of fungal material in a small percentage (~10%) of cells, suggesting the presence of infection. Importantly, this immunopositive material was absent in control samples. Confocal microscopy indicated that this fungal material had an intracellular localization. The specific morphology of this material varied between patients; in some instances, disseminated material was localized to the cytoplasm, whereas small punctate bodies were detected in other patients. Interestingly, fungal material could be revealed using different anti-fungal antibodies, suggesting multiple infections. In summary, fungal infection can only be observed using specific anti-fungal antibodies and only a small percentage of cells contain fungi. Our findings provide an explanation for the hitherto elusive detection of fungi in AD brains, and are consistent with the idea that fungal cells are internalized inside neurons.

  8. Detergent-insoluble EAAC1/EAAT3 aberrantly accumulates in hippocampal neurons of Alzheimer's disease patients.

    PubMed

    Duerson, Kevin; Woltjer, Randall L; Mookherjee, Paramita; Leverenz, James B; Montine, Thomas J; Bird, Thomas D; Pow, David V; Rauen, Thomas; Cook, David G

    2009-04-01

    Disturbed glutamate homeostasis may contribute to the pathological processes involved in Alzheimer's disease (AD). Once glutamate is released from synapses or from other intracellular sources, it is rapidly cleared by glutamate transporters. EAAC1 (also called EAAT3 or SLC1A1) is the primary glutamate transporter in forebrain neurons. In addition to transporting glutamate, EAAC1 plays other roles in regulating GABA synthesis, reducing oxidative stress in neurons, and is important in supporting neuron viability. Currently, little is known about EAAC1 in AD. To address whether EAAC1 is disturbed in AD, immunohistochemistry was performed on tissue from hippocampus and frontal cortex of AD and normal control subjects matched for age and gender. While EAAC1 immunostaining in cortex appeared comparable to controls, in the hippocampus, EAAC1 aberrantly accumulated in the cell bodies and proximal neuritic processes of CA2-CA3 pyramidal neurons in AD patients. Biochemical analyses showed that Triton X-100-insoluble EAAC1 was significantly increased in the hippocampus of AD patients compared to both controls and Parkinson's disease patients. These findings suggest that aberrant glutamate transporter expression is associated with AD-related neuropathology and that intracellular accumulation of detergent-insoluble EAAC1 is a feature of the complex biochemical lesions in AD that include altered protein solubility.

  9. Alzheimer's disease biomarker discovery in symptomatic and asymptomatic patients: experimental approaches and future clinical applications.

    PubMed

    Ho, Lap; Fivecoat, Hayley; Wang, Jun; Pasinetti, Giulio Maria

    2010-01-01

    Alzheimer's disease (AD) is the most common form of dementia in the elderly. Current treatments for AD are not as effective as needed, nor is there any definitive antemortem diagnostic. Understanding the biological processes that occur during AD onset and/or progression will improve disease diagnosis and treatment. Recent applications of microarray technologies for analysis of messenger (m) RNA expression profiles have elucidated distinct changes in the brain as a function of AD dementia initiation and progression. However, mRNA analysis underestimates post-transcriptional modifications and therefore provides only a partial view of the molecular changes in the AD brain. Combining mRNA studies with protein expression analysis may provide a more global picture of the biological processes associated with AD dementia. Information gathered could lead to the development of select biological indices (biomarkers) for guiding AD diagnosis and therapy. We will provide a brief background on AD, followed by a review on the applications of microarray, proteomics, as well as microRNA expression profile analysis to develop novel diagnostic strategies that may be useful for the diagnosis AD and for monitoring disease progression. The availability of biomarkers that promote early disease diagnosis, particularly among asymptomatic patients, will lead to the application of personalized medicine in AD.

  10. Deficits on irregular verbal morphology in Italian-speaking Alzheimer's disease patients

    PubMed Central

    Walenski, Matthew; Sosta, Katiuscia; Cappa, Stefano; Ullman, Michael T.

    2010-01-01

    Studies of English have shown that temporal-lobe patients, including those with Alzheimer's disease, are spared at processing real and novel regular inflected forms (e.g., blick → blicked; walk → walked), but impaired at real and novel irregular forms (e.g., spling → splang; dig → dug). Here we extend the investigation cross-linguistically to the more complex system of Italian verbal morphology, allowing us to probe the generality of the previous findings in English, as well as to test different explanatory accounts of inflectional morphology. We examined the production of real and novel regular and irregular past-participle and present-tense forms by native Italian-speaking healthy control subjects and patients with probable Alzheimer's disease. Compared to the controls, the patients were impaired at inflecting real irregular verbs but not real regular verbs both for past-participle and present-tense forms, but were not impaired at real regular verbs either for past-participle or present-tense forms. For novel past participles, the patients exhibited this same pattern of impaired production of class II (irregular) forms but spared class I (regular) production. In the present tense, patients were impaired at the production of class II forms (which are regular in the present tense), but spared at production of class I (regular) forms. Contrary to the pattern observed in English, the errors made by the patients on irregulars did not reveal a predominance of regularization errors (e.g., dig → digged). The findings thus partly replicate prior findings from English, but also reveal new patterns from a language with a more complex morphological system that includes verb classes (which are not possible to test in English). The demonstration of an irregular deficit following temporal-lobe damage in a language other than English reveals the cross-linguistic generality of the basic effect, while also elucidating important language-specific differences in the neuro

  11. Pharmacogenomics in Alzheimer's disease.

    PubMed

    Cacabelos, Ramón

    2008-01-01

    Pharmacological treatment in Alzheimer's disease (AD) accounts for 10-20% of direct costs, and fewer than 20% of AD patients are moderate responders to conventional drugs (donepezil, rivastigmine, galantamine, memantine), with doubtful cost-effectiveness. Both AD pathogenesis and drug metabolism are genetically regulated complex traits in which hundreds of genes cooperatively participate. Structural genomics studies demonstrated that more than 200 genes might be involved in AD pathogenesis regulating dysfunctional genetic networks leading to premature neuronal death. The AD population exhibits a higher genetic variation rate than the control population, with absolute and relative genetic variations of 40-60% and 0.85-1.89%, respectively. AD patients also differ in their genomic architecture from patients with other forms of dementia. Functional genomics studies in AD revealed that age of onset, brain atrophy, cerebrovascular hemodynamics, brain bioelectrical activity, cognitive decline, apoptosis, immune function, lipid metabolism dyshomeostasis, and amyloid deposition are associated with AD-related genes. Pioneering pharmacogenomics studies also demonstrated that the therapeutic response in AD is genotype-specific, with apolipoprotein E (APOE) 4/4 carriers the worst responders to conventional treatments. About 10-20% of Caucasians are carriers of defective cytochrome P450 (CYP) 2D6 polymorphic variants that alter the metabolism and effects of AD drugs and many psychotropic agents currently administered to patients with dementia. There is a moderate accumulation of AD-related genetic variants of risk in CYP2D6 poor metabolizers (PMs) and ultrarapid metabolizers (UMs), who are the worst responders to conventional drugs. The association of the APOE-4 allele with specific genetic variants of other genes (e.g., CYP2D6, angiotensin-converting enzyme [ACE]) negatively modulates the therapeutic response to multifactorial treatments affecting cognition, mood, and behavior

  12. Alzheimer's Patients' Use of Painkilling Patches Cause for Concern

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_162442.html Alzheimer's Patients' Use of Painkilling Patches Cause for Concern Researchers ... opioid painkillers may be common among Alzheimer's disease patients and could be a cause for concern, researchers ...

  13. Overexpression of Cell Cycle Proteins of Peripheral Lymphocytes in Patients with Alzheimer's Disease

    PubMed Central

    Kim, Hyeran; Kwon, Young-Ah; Ahn, Inn Sook; Kim, Sangha; Kim, Seonwoo; Jo, Sangmee Ahn

    2016-01-01

    Objective Biological markers for Alzheimer's disease (AD) will help clinicians make objective diagnoses early during the course of dementia. Previous studies have suggested that cell cycle dysregulation begins earlier than the onset of clinical manifestations in AD. Methods We examined the lymphocyte expression of cell cycle proteins in AD patients, dementia controls (DC), and normal controls (NC). One-hundred seventeen subjects (36 AD, 31 DC, and 50 NC) were recruited. The cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were measured in peripheral lymphocytes. Cell cycle protein expression in the three groups was compared after adjusting for age and sex. Results The levels of cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were significantly higher in AD patients than in the NC subjects. The DC group manifested intermediate levels of cell cycle proteins compared with the AD patients and the NC subjects. The present study indicates that cell cycle proteins are upregulated in the peripheral lymphocytes of AD patients. Conclusion Cell cycle dysregulation in peripheral lymphocytes may present a promising starting point for identifying peripheral biomarkers of AD. PMID:26766955

  14. Increased cortical atrophy in patients with Alzheimer's disease and type 2 diabetes mellitus

    PubMed Central

    Biessels, G J; De Leeuw, F‐E; Lindeboom, J; Barkhof, F; Scheltens, P

    2006-01-01

    Background The risk of Alzheimer's disease (AD) is increased in type 2 diabetes (DM2). This increased risk has been attributed to vascular comorbidity, but other mechanisms, such as accelerated ageing of the brain, have also been implicated. Objective To determine whether AD in patients with DM2 is associated with an increased occurrence of vascular lesions in the brain, by increased cerebral atrophy, or a combination of both. Methods In total, 29 patients with AD and DM2 and 58 patients with AD and without DM2 were included in the study. Clinical characteristics were recorded, and a neuropsychological examination and magnetic resonance imaging (MRI) scan were performed. MRI scans were rated for cortical and subcortical atrophy, medial temporal lobe atrophy, white matter lesions, and infarcts. Results The neuropsychological profiles of the two groups were identical. Patients with AD and DM2 had increased cortical atrophy on MRI (p<0.05) compared with the non‐DM2 group. In addition, infarcts were more common (odds ratio 2.4; 95% CI 0.8 to 7.8), but this effect did not account for the increased atrophy. The other MR measures did not differ between the groups. Conclusion The results suggest that non‐vascular mechanisms, leading to increased cortical atrophy, are also involved in the increased risk of AD in DM2. PMID:16484636

  15. Mitochondrial Alterations in Peripheral Mononuclear Blood Cells from Alzheimer's Disease and Mild Cognitive Impairment Patients.

    PubMed

    Delbarba, A; Abate, G; Prandelli, C; Marziano, M; Buizza, L; Arce Varas, N; Novelli, A; Cuetos, F; Martinez, C; Lanni, C; Memo, M; Uberti, D

    2016-01-01

    It is well recognized that mitochondrial dysfunction contributes to neurodegeneration occurring in Alzheimer's disease (AD). However, evidences of mitochondrial defects in AD peripheral cells are still inconclusive. Here, some mitochondrial-encoded and nuclear-encoded proteins, involved in maintaining the correct mitochondria machine, were investigated in terms of protein expression and enzymatic activity in peripheral blood mononuclear cells (PBMCs) isolated from AD and Mild Cognitive Impairment (MCI) patients and healthy subjects. In addition mitochondrial DNA copy number was measured by real time PCR. We found some differences and some similarities between AD and MCI patients when compared with healthy subjects. For example, cytochrome C and cytochrome B were decreased in AD, while MCI showed only a statistical reduction of cytochrome C. On the other hand, both AD and MCI blood cells exhibited highly nitrated MnSOD, index of a prooxidant environment inside the mitochondria. TFAM, a regulator of mitochondrial genome replication and transcription, was decreased in both AD and MCI patients' blood cells. Moreover also the mitochondrial DNA amount was reduced in PBMCs from both patient groups. In conclusion these data confirmed peripheral mitochondria impairment in AD and demonstrated that TFAM and mtDNA amount reduction could be two features of early events occurring in AD pathogenesis.

  16. Fungal Enolase, β-Tubulin, and Chitin Are Detected in Brain Tissue from Alzheimer's Disease Patients.

    PubMed

    Pisa, Diana; Alonso, Ruth; Rábano, Alberto; Horst, Michael N; Carrasco, Luis

    2016-01-01

    Recent findings provide evidence that fungal structures can be detected in brain tissue from Alzheimer's disease (AD) patients using rabbit polyclonal antibodies raised against whole fungal cells. In the present work, we have developed and tested specific antibodies that recognize the fungal proteins, enolase and β-tubulin, and an antibody that recognizes the fungal polysaccharide chitin. Consistent with our previous studies, a number of rounded yeast-like and hyphal structures were detected using these antibodies in brain sections from AD patients. Some of these structures were intracellular and, strikingly, some were found to be located inside nuclei from neurons, whereas other fungal structures were detected extracellularly. Corporya amylacea from AD patients also contained enolase and β-tubulin as revealed by these selective antibodies, but were devoid of fungal chitin. Importantly, brain sections from control subjects were usually negative for staining with the three antibodies. However, a few fungal structures can be observed in some control individuals. Collectively, these findings indicate the presence of two fungal proteins, enolase and β-tubulin, and the polysaccharide chitin, in CNS tissue from AD patients. These findings are consistent with our hypothesis that AD is caused by disseminated fungal infection.

  17. Lack of contextual-word predictability during reading in patients with mild Alzheimer disease.

    PubMed

    Fernández, Gerardo; Manes, Facundo; Rotstein, Nora P; Colombo, Oscar; Mandolesi, Pablo; Politi, Luis E; Agamennoni, Osvaldo

    2014-09-01

    In the present work we analyzed the effect of contextual word predictability on the eye movement behavior of patients with mild Alzheimer disease (AD) compared to age-matched controls, by using the eyetracking technique and lineal mixed models. Twenty AD patients and 40 age-matched controls participated in the study. We first evaluated gaze duration during reading low and highly predictable sentences. AD patients showed an increase in gaze duration, compared to controls, both in sentences of low or high predictability. In controls, highly predictable sentences led to shorter gaze durations; by contrary, AD patients showed similar gaze durations in both types of sentences. Similarly, gaze duration in controls was affected by the cloze predictability of word N and N+1, whereas it was the same in AD patients. In contrast, the effects of word frequency and word length were similar in controls and AD patients. Our results imply that contextual-word predictability, whose processing is proposed to require memory retrieval, facilitated reading behavior in healthy subjects, but this facilitation was lost in early AD patients. This loss might reveal impairments in brain areas such as those corresponding to working memory, memory retrieval, and semantic memory functions that are already present at early stages of AD. In contrast, word frequency and length processing might require less complex mechanisms, which were still retained by AD patients. To the best of our knowledge, this is the first study measuring how patients with early AD process well-defined words embedded in sentences of high and low predictability. Evaluation of the resulting changes in eye movement behavior might provide a useful tool for a more precise early diagnosis of AD.

  18. [Therapy of Alzheimer disease].

    PubMed

    Kovács, Tibor

    2009-03-01

    Dementia is one of the most important health problems in the aging populations. The most frequent cause of it is Alzheimer's disease (AD) which is characterized by intracellular neuro-fibrillary tangles (NFT) and the extracellular senile plaques. The NFTs are mainly formed by the hyperphosphorylated microtubule-binding protein, the tau, while the senile plaques are composed of beta-amyloid protein cleaved from the amyloid precursor protein (APP) by the beta- and gamma-secretases. The pharmacotherapy of AD consists of symptomatic and disease-modifying therapies. The most frequently used therapeutic agents are the nootropic drugs supported by personal rather evidence based experiences. The leading-edge therapy of AD at present is the inhibition of the acetylcholine-esterase enzyme (AChEI) with mainly cognitive symptomatic and weak disease-modifying effects; they are licensed in the mild and middle stages of AD (MMSE 26-10), but their effect is proved in the severe stage of the disease and they are effective in the management of the neuropsychiatric symptoms too. Memantine (which is an inhibitor of the N-metil-D-aspartate receptor) is used in the middle and severe stages of AD and it can be effectively combined with AChEIs. The future therapy of AD will possibly be a "causative" therapy. The most frequent directions are therapies aiming to decrease the production or the deposition of beta-amyloid peptide. The active vaccination study of AN-1792 was terminated because of immunological side-effects, but several active and passive immunisation therapies are in development nowadays. It is also possible to inhibit the aggregation of the beta-amyloid peptide with peptide fragments or with Cu2+ and Zn2+ ion chelators. A promising direction is the inhibition of the enzymes responsible for the production of the beta-amyloid peptide: beta-secretase inhibitors with low molecular weight and penetrability through the blood-brain barrier are developed while the inhibitors of the

  19. Relationship of physical and functional independence and perceived quality of life of veteran patients with Alzheimer disease.

    PubMed

    Yeaman, Paul A; Kim, Dong-Yun; Alexander, Jeffrey L; Ewing, Helen; Kim, Kye Y

    2013-08-01

    Alzheimer disease not only affects the cognitive function but also impacts one's abilities to perform daily tasks. This study evaluated for correlation between the quality of life of patients with Alzheimer disease (QoL-AD) and the level of independence and to evaluate the statistical difference between patients' quality of life and proxy perception of quality of life by utilizing the Katz activities of daily living and QoL-AD on patients and QoL-AD on caregivers. There was a small positive correlation (r = .13) between the levels of physical and functional independence and the perceived QoL. Also, patient consistently had higher QoL-AD than their caregiver counterparts. These findings provide some insight into our need to acknowledge factors that may influence QoL and illustrate the importance of monitoring for executive dysfunction and the safety risk.

  20. Haloperidol disrupts, clozapine reinstates the circadian rest-activity cycle in a patient with early-onset Alzheimer disease.

    PubMed

    Wirz-Justice, A; Werth, E; Savaskan, E; Knoblauch, V; Gasio, P F; Müller-Spahn, F

    2000-01-01

    Measurement of the circadian rest-activity cycle in a patient with early-onset Alzheimer disease for 555 days revealed marked changes in the timing and amount of nocturnal activity. After neuroleptic medication was changed to haloperidol, the rest-activity cycle became completely arrhythmic for two months, concomitant with a marked worsening of cognitive state. Circadian integrity returned together with clinical improvement when the patient was subsequently treated with clozapine. This observation suggests that the known tendency for patients with Alzheimer disease to develop sleep-wake cycle disturbances may be aggravated by a classic neuroleptic; in contrast, the atypical neuroleptic clozapine may consolidate it. Similar observations in schizophrenic patients indicate that this chronobiological finding is drug- and not illness-related.

  1. Alzheimer's disease: early diagnosis and treatment.

    PubMed

    Chu, L W

    2012-06-01

    With ageing of populations, the worldwide population of persons with dementia will reach over 81 million by 2040, of which the most common cause is Alzheimer's disease. In recent years, there have been major advances in the understanding of its pathogenesis, methods to diagnose it, and treatment. Magnetic resonance brain imaging, cerebrospinal fluid biomarkers, and Pittsburgh compound B and fluorodeoxyglucose positron emission tomography of the brain can facilitate an accurate diagnosis of Alzheimer's disease in its early stage, and diagnose the mild cognitive impairment stage of Alzheimer's disease. At present, only symptomatic but not disease-modifying drug treatments are available. Donepezil, rivastigmine and galantamine are the currently approved cholinesterase inhibitors for the treatment of mild, moderate, and severe Alzheimer's disease. Overall, cholinesterase inhibitors show beneficial effects on cognition, activity of daily living, behaviour, and overall clinical rating. Memantine is another symptomatic treatment for moderate-to-severe Alzheimer's disease patients. It has a small beneficial effect on cognition, activity of daily living, behaviour, and overall clinical rating. Vitamin E has antioxidant properties, and may be used in some Alzheimer's disease patients without vascular risk factors. Concurrent non-pharmacological and psychosocial management of patients and their caregivers have a very important role. Disease-modifying therapies are still under development, whilst immunotherapy may be a viable option in the near future.

  2. Antioxidant therapies for Alzheimer's disease.

    PubMed

    Feng, Ye; Wang, Xiaochuan

    2012-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disease featuring progressive impairments in memory, cognition, and behavior and ultimately leads to death. The histopathological changes of Alzheimer's disease include neuronal and synaptic loss, formation of extracellular senile plaques and intracellular neurofibrillary tangles in brain. Multiple lines of evidence indicate that oxidative stress not only strongly participates in an early stage of Alzheimer's disease prior to cytopathology, but plays an important role in inducing and activating multiple cell signaling pathways that contribute to the lesion formations of toxic substances and then promotes the development of Alzheimer's disease. Many years of studies show that antioxidant therapies have enjoyed general success in preclinical studies. Therefore, this paper mainly focuses on the recent developments of common used antioxidant therapies for Alzheimer's disease and thus provides indications for future potential antioxidant therapeutic strategies of neurodegenerative diseases.

  3. [Key points of the follow-up plan in the care of Alzheimer's disease patients].

    PubMed

    Hein, C; Sourdet, S; Piau, A; Villars, H; Nourhashemi, F; Vellas, B

    2011-03-01

    The following article presents the main points of the follow-up plan of Alzheimer's disease (AD) and related syndromes patients. The general objective of this follow-up plan is to improve the quality of live of these subjects and their family. The key points are assessments of cognitive decline, functional decline and complications such as behavioural and psychological symptoms of dementia (BPSD), malnutrition and gait and balance disorders. In clinical practice, different tools are available, but frequency of evaluation is not consensual. However, the aim of this follow-up is to detect, prevent and treat complications and to improve the use of residual functional abilities in basic activities of daily living. The physician also needs to detect and prevent caregiver's exhaustion and to consider the ethical issues raised by the disease. The care plan is based on non pharmacological and pharmacological measures. The non pharmacological approach must be implemented first. The place of anti-dementia drugs is considered. Lastly, this follow-up plan aims to limit iterative admissions to emergency room and to increase the access to geriatric units. Communication and collaboration between specialist, family practitioner and caregivers are needed in order to reach the objective of quality of life improvement in AD patients.

  4. Patients with mild Alzheimer's disease produced shorter outgoing saccades when reading sentences.

    PubMed

    Fernández, Gerardo; Schumacher, Marcela; Castro, Liliana; Orozco, David; Agamennoni, Osvaldo

    2015-09-30

    In the present work we analyzed forward saccades of thirty five elderly subjects (Controls) and of thirty five mild Alzheimer's disease (AD) during reading regular and high-predictable sentences. While they read, their eye movements were recorded. The pattern of forward saccade amplitudes as a function of word predictability was clearly longer in Controls. Our results suggest that Controls might use stored information of words for enhancing their reading performance. Further, cloze predictability increased outgoing saccades amplitudes, as this increase stronger in high-predictable sentences. Quite the contrary, patients with mild AD evidenced reduced forward saccades even at early stages of the disease. This reduction might reveal impairments in brain areas such as those corresponding to working memory, memory retrieval, and semantic memory functions that are already present at early stages of AD. Our findings might be relevant for expanding the options for the early detection and monitoring of in the early stages of AD. Furthermore, eye movements during reading could provide a new tool for measuring a drug's impact on patient's behavior.

  5. Tau prions from Alzheimer's disease and chronic traumatic encephalopathy patients propagate in cultured cells.

    PubMed

    Woerman, Amanda L; Aoyagi, Atsushi; Patel, Smita; Kazmi, Sabeen A; Lobach, Iryna; Grinberg, Lea T; McKee, Ann C; Seeley, William W; Olson, Steven H; Prusiner, Stanley B

    2016-12-13

    Tau prions are thought to aggregate in the central nervous system, resulting in neurodegeneration. Among the tauopathies, Alzheimer's disease (AD) is the most common, whereas argyrophilic grain disease (AGD), corticobasal degeneration (CBD), chronic traumatic encephalopathy (CTE), Pick's disease (PiD), and progressive supranuclear palsy (PSP) are less prevalent. Brain extracts from deceased individuals with PiD, a neurodegenerative disorder characterized by three-repeat (3R) tau prions, were used to infect HEK293T cells expressing 3R tau fused to yellow fluorescent protein (YFP). Extracts from AGD, CBD, and PSP patient samples, which contain four-repeat (4R) tau prions, were transmitted to HEK293 cells expressing 4R tau fused to YFP. These studies demonstrated that prion propagation in HEK cells requires isoform pairing between the infecting prion and the recipient substrate. Interestingly, tau aggregates in AD and CTE, containing both 3R and 4R isoforms, were unable to robustly infect either 3R- or 4R-expressing cells. However, AD and CTE prions were able to replicate in HEK293T cells expressing both 3R and 4R tau. Unexpectedly, increasing the level of 4R isoform expression alone supported the propagation of both AD and CTE prions. These results allowed us to determine the levels of tau prions in AD and CTE brain extracts.

  6. How to calculate an MMSE score from a MODA score (and vice versa) in patients with Alzheimer's disease.

    PubMed

    Cazzaniga, R; Francescani, A; Saetti, C; Spinnler, H

    2003-11-01

    The aim of the present study was to provide a statistically sound way of reciprocally converting scores of the mini-mental state examination (MMSE) and the Milan overall dementia assessment (MODA). A consecutive series of 182 patients with "probable" Alzheimer's disease patients was examined with both tests. MODA and MMSE scores proved to be highly correlated. A formula for converting MODA and MMSE scores was generated.

  7. Role of Methylglyoxal in Alzheimer's Disease

    PubMed Central

    Zambonin, Laura; Hrelia, Silvana

    2014-01-01

    Alzheimer's disease is the most common and lethal neurodegenerative disorder. The major hallmarks of Alzheimer's disease are extracellular aggregation of amyloid β peptides and, the presence of intracellular neurofibrillary tangles formed by precipitation/aggregation of hyperphosphorylated tau protein. The etiology of Alzheimer's disease is multifactorial and a full understanding of its pathogenesis remains elusive. Some years ago, it has been suggested that glycation may contribute to both extensive protein cross-linking and oxidative stress in Alzheimer's disease. Glycation is an endogenous process that leads to the production of a class of compounds known as advanced glycation end products (AGEs). Interestingly, increased levels of AGEs have been observed in brains of Alzheimer's disease patients. Methylglyoxal, a reactive intermediate of cellular metabolism, is the most potent precursor of AGEs and is strictly correlated with an increase of oxidative stress in Alzheimer's disease. Many studies are showing that methylglyoxal and methylglyoxal-derived AGEs play a key role in the etiopathogenesis of Alzheimer's disease. PMID:24734229

  8. Learning to Perceive Structure from Motion and Neural Plasticity in Patients with Alzheimer's Disease

    ERIC Educational Resources Information Center

    Kim, Nam-Gyoon; Park, Jong-Hee

    2010-01-01

    Recent research has demonstrated that Alzheimer's disease (AD) affects the visual sensory pathways, producing a variety of visual deficits, including the capacity to perceive structure-from-motion (SFM). Because the sensory areas of the adult brain are known to retain a large degree of plasticity, the present study was conducted to explore whether…

  9. Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease

    PubMed Central

    1996-01-01

    In Alzheimer's disease (AD), affected neurons accumulate beta amyloid protein, components of which can induce mouse microglia to express the high-output isoform of nitric oxide synthase (NOS2) in vitro. Products of NOS2 can be neurotoxic. In mice, NOS2 is normally suppressed by transforming growth factor beta 1 (TGF-beta 1). Expression of TGF-beta 1 is decreased in brains from AD patients, a situation that might be permissive for accumulation of NOS2. Accordingly, we investigated the expression of NOS2 in patients with AD, using three monospecific antibodies: a previously described polyclonal and two new monoclonal antibodies. Neurofibrillary tangle-bearing neurons and neuropil threads contained NOS2 in brains from each of 11 AD patients ranging in age from 47 to 81 years. NOS2 was undetectable in brains from 6 control subjects aged 23-72 years, but was expressed in small amounts in 3 control subjects aged 77-87 years. Thus, human neurons can express NOS2 in vivo. The high-output pathway of NO production may contribute to pathogenesis in AD. PMID:8879214

  10. Modifications of the endosomal compartment in peripheral blood mononuclear cells and fibroblasts from Alzheimer's disease patients

    PubMed Central

    Corlier, F; Rivals, I; Lagarde, J; Hamelin, L; Corne, H; Dauphinot, L; Ando, K; Cossec, J-C; Fontaine, G; Dorothée, G; Malaplate-Armand, C; Olivier, J-L; Dubois, B; Bottlaender, M; Duyckaerts, C; Sarazin, M; Potier, M-C; Alnajjar-Carpentier, Dr Amer; Logak, Dr Michel; Leder, Dr Sara; Marchal, Dr Dominique; Pitti-Ferandi, Dr Hélène; Brugeilles, Dr Hélene; Roualdes, Dr Brigitte; Michon, Dr Agnes

    2015-01-01

    Identification of blood-based biomarkers of Alzheimer's disease (AD) remains a challenge. Neuropathological studies have identified enlarged endosomes in post-mortem brains as the earliest cellular change associated to AD. Here the presence of enlarged endosomes was investigated in peripheral blood mononuclear cells from 48 biologically defined AD patients (25 with mild cognitive impairment and 23 with dementia (AD-D)), and 23 age-matched healthy controls using immunocytochemistry and confocal microscopy. The volume and number of endosomes were not significantly different between AD and controls. However, the percentage of cells containing enlarged endosomes was significantly higher in the AD-D group as compared with controls. Furthermore, endosomal volumes significantly correlated to [C11]PiB cortical index measured by positron emission tomography in the AD group, independently of the APOE genotype, but not to the levels of amyloid-beta, tau and phosphorylated tau measured in the cerebrospinal fluid. Importantly, we confirmed the presence of enlarged endosomes in fibroblasts from six unrelated AD-D patients as compared with five cognitively normal controls. This study is the first, to our knowledge, to report morphological alterations of the endosomal compartment in peripheral cells from AD patients correlated to amyloid load that will now be evaluated as a possible biomarker. PMID:26151923

  11. Ion beam analysis of the bone tissue of Alzheimer's disease patients

    NASA Astrophysics Data System (ADS)

    Robertson, J. D.; Samudralwar, D. L.; Markesbery, W. R.

    1992-02-01

    It has been hypothesized that perturbations in element metabolism play a role in the etiology and/or pathogenesis of Alzheimer's disease (AD). No conclusion regarding this hypothesis has been reached, however, as results for central nervous system tissues from different research groups are contradictory. We are currently utilizing external-beam thick-target FIXE and PIGE analyses to investigate the elemental concentrations in the bone tissue of AD patients. Because bone acts as a "repository" for many trace elements, these measurements should provide information on the long-term trace-element status of AD patients. With the simultaneous PIXE/PIGE measurements, we are able to instrumentally determine the concentrations of oxygen, phosphorus, calcium, and 12-15 minor and trace elements in a single 30 min irradiation. Initial results obtained from the IBA measurements of both cortical and trabecular bone autopsy samples from four AD patients and twelve age-matched controls indicate a possible imbalance in Zn, Br and Rb.

  12. Characteristics of number transcoding errors of Chinese- versus English-speaking Alzheimer's disease patients.

    PubMed

    Ting, Simon Kang Seng; Chia, Pei Shi; Kwek, Kevin; Tan, Wilnard; Hameed, Shahul

    2016-10-01

    Number processing disorder is an acquired deficit in mathematical skills commonly observed in Alzheimer's disease (AD), usually as a consequence of neurological dysfunction. Common impairments include syntactic errors (800012 instead of 8012) and intrusion errors (8 thousand and 12 instead of eight thousand and twelve) in number transcoding tasks. This study aimed to understand the characterization of AD-related number processing disorder within an alphabetic language (English) and ideographical language (Chinese), and to investigate the differences between alphabetic and ideographic language processing. Chinese-speaking AD patients were hypothesized to make significantly more intrusion errors than English-speaking ones, due to the ideographical nature of both Chinese characters and Arabic numbers. A simplified number transcoding test derived from EC301 battery was administered to AD patients. Chinese-speaking AD patients made significantly more intrusion errors (p = 0.001) than English speakers. This demonstrates that number processing in an alphabetic language such as English does not function in the same manner as in Chinese. The impaired inhibition capability likely contributes to such observations due to its competitive lexical representation in brain for Chinese speakers.

  13. The Effects of Donepezil on 15-Item Geriatric Depression Scale Structure in Patients with Alzheimer Disease

    PubMed Central

    Yang, Youngsoon; Kwak, Yong Tae

    2016-01-01

    Background/Aims In Alzheimer disease (AD), depression is among the most common accompanying neuropsychiatric symptoms and has different clinical manifestations when compared with early-life depression. In patients with drug-naïve AD, we tried to explore the structure of the 15-item Geriatric Depression Scale (GDS15) and the effect of donepezil on these substructures. Methods GDS15, cognitive function, and activities of daily living function tests were administered to 412 patients with probable AD who had not been medicated before visiting the hospital. Using principal component analysis, three factors were identified. The patients with AD who received only donepezil were retrospectively analyzed and we compared the change of cognition and GDS15 subgroup after donepezil medication. Results Our study identified three factors and revealed that the GDS15 may be comprised of a heterogeneous scale. The Barthel index was significantly correlated with factor 1 (positively) and factor 2 (negatively). The Korean version of the MMSE (K-MMSE) was significantly correlated with factor 2 and factor 3. Compared to the baseline state, K-MMSE and GDS15 showed significant improvement after taking donepezil. Among GDS15 subgroups, factor 2 and factor 3 showed significant improvement after donepezil treatment. Conclusions These results suggest that the GDS15 may be comprised of a heterogeneous scale and donepezil differentially affects the GDS15 subgroup in AD. PMID:27790242

  14. Genetic aspects of Alzheimer disease.

    PubMed

    Bird, Thomas D

    2008-04-01

    Alzheimer disease is the most common cause of dementia and represents a major public health problem. The neuropathologic findings of amyloid-beta plaques and tau containing neurofibrillary tangles represent important molecular clues to the underlying pathogenesis. Genetic factors are well recognized, but complicated. Three rare forms of autosomal-dominant early-onset familial Alzheimer disease have been identified and are associated with mutations in amyloid precursor protein, presenilin 1, and presenilin 2 genes. The more common late-onset form of Alzheimer disease is assumed to be polygenic/multifactorial. However, thus far the only clearly identified genetic risk factor for Alzheimer disease is Apo lipoprotein E. The epsilon4 allele of Apo lipoprotein E influences age at onset of Alzheimer disease, but is neither necessary nor sufficient for the disease. The search continues for the discovery of additional genetic influences.

  15. Alzheimer-type neuropathology in a 28 year old patient with iatrogenic Creutzfeldt-Jakob disease after dural grafting.

    PubMed

    Preusser, M; Ströbel, T; Gelpi, E; Eiler, M; Broessner, G; Schmutzhard, E; Budka, H

    2006-03-01

    We report the case of a 28 year old man who had received a cadaverous dura mater graft after a traumatic open skull fracture with tearing of the dura at the age of 5 years. A clinical suspicion of Creutzfeldt-Jakob disease (CJD) was confirmed by a brain biopsy 5 months prior to death and by autopsy, thus warranting the diagnosis of iatrogenic CJD (iCJD) according to WHO criteria. Immunohistochemistry showed widespread cortical depositions of disease associated prion protein (PrP(sc)) in a synaptic pattern, and western blot analysis identified PrP(sc) of type 2A according to Parchi et al. Surprisingly, we found Alzheimer-type senile plaques and cerebral amyloid angiopathy in widespread areas of the brain. Plaque-type and vascular amyloid was immunohistochemically identified as deposits of beta-A4 peptide. CERAD criteria for diagnosis of definite Alzheimer's disease (AD) were met in the absence of neurofibrillar tangles or alpha-synuclein immunoreactive inclusions. There was no family history of AD, CJD, or any other neurological disease, and genetic analysis showed no disease specific mutations of the prion protein, presenilin 1 and 2, or amyloid precursor protein genes. This case represents (a) the iCJD case with the longest incubation time after dural grafting reported so far, (b) the youngest documented patient with concomitant CJD and Alzheimer-type neuropathology to date, (c) the first description of Alzheimer-type changes in iCJD, and (d) the second case of iCJD in Austria. Despite the young patient age, the Alzheimer-type changes may be an incidental finding, possibly related to the childhood trauma.

  16. Genetics Home Reference: Alzheimer disease

    MedlinePlus

    ... 23(3):157-65. Review. Citation on PubMed Bird TD. Genetic aspects of Alzheimer disease. Genet Med. ... on PubMed or Free article on PubMed Central Bird TD. Genetic factors in Alzheimer's disease. N Engl ...

  17. Antibodies in Cerebrospinal Fluid of Some Alzheimer Disease Patients Recognize Cholinergic Neurons in the Rat Central Nervous System

    NASA Astrophysics Data System (ADS)

    McRae-Degueurce, Amanda; Booj, Serney; Haglid, Kenneth; Rosengren, Lars; Karlsson, Jan Erik; Karlsson, Ingvar; Wallin, Anders; Svennerholm, Lars; Gottfries, Carl-Gerhard; Dahlstrom, Annica

    1987-12-01

    The etiology of Alzheimer disease is unclear. However, immunological aberrations have been suggested to be critical factors in the pathogenesis of this neurodegenerative disease. This study was carried out to investigate if cerebrospinal fluid (CSF) from Alzheimer disease patients contains antibodies that recognize specific neuronal populations in the rat central nervous system. The results indicate that in a subgroup of patients this is indeed the case. The antibodies reported in this study have the following properties: (i) they recognize neuronal populations and components in the medial septum and spinal motor neurons in rats perfused with a mixture that fixes small neurotransmitter molecules; (ii) adsorption of the patient CSF with staphylococcal protein A-Sepharose and using a polyclonal antiserum against human IgG3 indicates that the immunocytochemical reaction in these brain regions is mainly due to the subclass IgG3; and (iii) the CSF immunocytochemical reaction is blocked by preincubation of the sections with a rabbit anti-acetylcholine antiserum. These results provide evidence that antibodies in the CSF of some, but not all, Alzheimer disease patients recognize acetylcholine-like epitopes in cholinergic neurons in the rat central nervous system.

  18. Serum Uric Acid Levels in Patients with Alzheimer's Disease: A Meta-Analysis

    PubMed Central

    Chen, Xueping; Guo, Xiaoyan; Huang, Rui; Chen, Yongping; Zheng, Zhenzhen; Shang, Huifang

    2014-01-01

    Background Serum uric acid (UA) could exert neuro-protective effects against Alzheimer's disease (AD) via its antioxidant capacities. Many studies investigated serum UA levels in AD patients, but to date, results from these observational studies are conflicting. Methods We conducted a meta-analysis to compare serum UA levels between AD patients and healthy controls by the random-effects model. Studies were identified by searching PubMed, ISI Web of Science, EMBASE, and the Cochrane library databases from 1966 through July 2013 using the Medical Subject Headings and keywords without restriction in languages. Only case-control studies were included if they had data on serum UA levels in AD patients and healthy controls. Begg's funnel plot and Egger's regression test were applied to assess the potential publication bias. Sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity. Results A total of 11 studies met the inclusion criteria including 2708 participants were abstracted. Serum UA levels were not significantly different in AD patients compared to healthy controls (standardized mean difference (SMD) = −0.50; 95% confidence interval (CI): −1.23 to 0.22). Little evidence of publication bias was observed. Sensitivity analyses showed that the combined SMD was consistent every time omitting any one study, except only one study which greatly influenced the overall results. Meta-regression showed that year of publication, race, sample size, and mean age were not significant sources of heterogeneity. Conclusion Our meta-analysis of case-control studies suggests that serum UA levels do not differ significantly in AD patients, but there may be a trend toward decreased UA in AD after an appropriate interpretation. More well-designed investigations are needed to demonstrate the potential change of serum UA levels in AD patients. PMID:24714617

  19. Plasma antibodies to Abeta40 and Abeta42 in patients with Alzheimer's disease and normal controls.

    PubMed

    Xu, Wuhua; Kawarabayashi, Takeshi; Matsubara, Etsuro; Deguchi, Kentaro; Murakami, Tetsuro; Harigaya, Yasuo; Ikeda, Masaki; Amari, Masakuni; Kuwano, Ryozo; Abe, Koji; Shoji, Mikio

    2008-07-11

    Antibodies to amyloid beta protein (Abeta) are present naturally or after Abeta vaccine therapy in human plasma. To clarify their clinical role, we examined plasma samples from 113 patients with Alzheimer's disease (AD) and 205 normal controls using the tissue amyloid plaque immunoreactivity (TAPIR) assay. A high positive rate of TAPIR was revealed in AD (45.1%) and age-matched controls (41.2%), however, no significance was observed. No significant difference was observed in the MMS score or disease duration between TAPIR-positive and negative samples. TAPIR-positive plasma reacted with the Abeta40 monomer and dimer, and the Abeta42 monomer weakly, but not with the Abeta42 dimer. TAPIR was even detected in samples from young normal subjects and young Tg2576 transgenic mice. Although the Abeta40 level and Abeta40/42 ratio increased, and Abeta42 was significantly decreased in plasma from AD groups when compared to controls, no significant correlations were revealed between plasma Abeta levels and TAPIR grading. Thus an immune response to Abeta40 and immune tolerance to Abeta42 occurred naturally in humans without a close relationship to the Abeta burden in the brain. Clarification of the mechanism of the immune response to Abeta42 is necessary for realization of an immunotherapy for AD.

  20. Behavioural symptoms in patients with Alzheimer's disease and their association with cognitive impairment

    PubMed Central

    2010-01-01

    Background Behavioural and psychological symptoms of dementia (BPSD) are non-cognitive symptoms commonly associated to Alzheimer's disease (AD). The characterization of the clinical profile of AD patients might help to better understand disease evolution and to improve diagnosis and treatment. Thus, the aim of the present study is to describe the clinical profile of AD patients, and to correlate the presence of BPSD with the severity of the disease. Methods A cross-sectional, observational and multicenter study was conducted at 115 centres in Spain. Patients suffering from AD with higher and lower BPSD scores (ADAS-Noncog score 26-50 and ≤25, respectively) were included. Demographic and clinical data were collected, and dementia severity was assessed by the Mini Mental State Examination (MMSE) [mild 27-21, moderate 20-11, severe ≤10]. The use of ADAS-Noncog in clinical practice was also explored. Results A total of 1014 patients (463 with higher and 551 with lower BPSD scores) were included (mean age 77 ± 7 years, 65% women). Almost all patients (90%) had BPSD at inclusion, 17% of which reported psychotic outbreaks. The most prevalent symptoms were lack of concentration (56%), tremors (56%), depression (44%), lack of cooperation (36%), and delusions (32%). Patients with higher BPSD scores showed a significantly higher prevalence of psychotic symptoms (delusions, hallucinations, and delirium) and tremors, while emotional symptoms (tearfulness and apathy) predominated in patients with lower BPSD scores. MMSE and ADAS-Noncog scores were negatively associated (p = 0.0284), suggesting a correlation between cognitive impairment and BPSD. Lack of concentration and appetite change significantly correlated with MMSE (p = 0.0472 and p = 0.0346, respectively). Rivastigmine and donepezil were the first choice therapies in mild to moderate dementia. ADAS-Noncog was generally considered better or similar to other scales (82%), and 68% of the investigators were willing to

  1. Cholinesterase inhibitors are compatible with psychosocial intervention for Alzheimer disease patients suggested by neuroimaging findings.

    PubMed

    Meguro, Kenichi

    2017-01-30

    We previously reported that the frontal lobe was stimulated by psychosocial intervention for dementia patients, and that the parietal lobe was associated with logical judgment. We hypothesized that the combined therapeutic approach with symptomatic drug treatment can directly stimulate not only attention function but also judgment function indirectly to observing other participants' behaviors. Fifty-two patients with Alzheimer disease underwent the group reminiscence approach with reality orientation, as well as the donepezil treatment. The cerebral blood flow (CBF) was assessed with (99m)Tc-ECD SPECT. Two analyses were performed: Analysis 1 was to compare Responders vs. Non-responders as shown by MMSE scores, whereas Analysis 2 was to compare Good vs. Poor reminders of the intervention content. We found that the CBF in the frontal lobe was significantly higher in Responders (vs. Non-responders). The CBF in the parietal lobe, especially the left side, was significantly higher in the Good reminders (vs. Poor reminders). The donepezil stimulated the areas similar to where the psychosocial intervention was previously found to be stimulated directly, thus the drug was thought to be compatible for psychosocial intervention. The parietal lobe was stimulated indirectly, suggesting that the indirect effect of the intervention may be based on logical judgment function.

  2. Information content versus relational knowledge: semantic deficits in patients with Alzheimer's disease.

    PubMed

    Aronoff, Justin M; Gonnerman, Laura M; Almor, Amit; Arunachalam, Sudha; Kempler, Daniel; Andersen, Elaine S

    2006-01-01

    Studies of semantic impairment in Alzheimer's disease (AD) have yielded conflicting results, some finding evidence of considerable deficits, others finding that semantic knowledge is relatively intact. How do we reconcile findings from picture naming tasks that seem to indicate semantic impairment in AD with results from certain sorting tasks that suggest intact semantics? To investigate the basis of the contradictory results described above, we conducted a study using two types of tasks: (1) picture naming; and (2) board sorting. The board sorting task we used is a simultaneous similarity judgment task, in which participants are asked to place more similar concepts closer together and less similar ones farther apart. We compared the performance of AD patients on these two tasks, using a number of different analyses that yield very different patterns of results. Our results indicate that whether patients show impairment or not depends on both the nature of the task and the subsequent analysis chosen. Specifically, tasks and analyses that focus on relational knowledge (e.g., dog is more related to cat than to camel) lead to different conclusions than those based on specific information about individual items. These findings suggest that the board sorting method, when coupled with multiple analyses, provides a more complete picture of the underlying semantic deficit in AD than previous studies have shown.

  3. Reduced sulfotransferase SULT2A1 activity in patients with Alzheimer's disease.

    PubMed

    Vaňková, M; Hill, M; Velíková, M; Včelák, J; Vacínová, G; Lukášová, P; Vejražková, D; Dvořáková, K; Rusina, R; Holmerová, I; Jarolímová, E; Vaňková, H; Bendlová, B

    2015-01-01

    Steroids are important components in the pathophysiology of Alzheimer's disease (AD). Although their role has been studied, the corresponding metabolomic data is limited. In the present study we evaluate the role of steroid sulfotransferase SULT2A1 in the pathophysiology of AD on the basis of circulating steroids (measured by GC-MS), in which the sulfation catalyzed by SULT2A1 dominates over glucuronidation (pregnenolone/sulfate, DHEA/sulfate, androstenediol/sulfate and 5alpha-reduced pregnane and androstane catabolites). To estimate a general trend of SUL2A1 activity in AD patients we compared the ratios of steroid conjugates to their unconjugated counterparts (C/U) in controls (11 men and 22 women) and AD patients (18 men and 16 women) for individual circulating steroids after adjustment for age and BMI using ANCOVA model including the factors AD status and gender. Decreased C/U ratio for the C19 steroids demonstrate an association between attenuated sulfation of C19 steroids in adrenal zona reticularis and the pathophysiology of AD.

  4. Neuroprotective Effects of Cistanches Herba Therapy on Patients with Moderate Alzheimer's Disease

    PubMed Central

    Li, Nan; Wang, Jianping; Ma, Jun; Gu, Zhiqiang; Jiang, Chao; Yu, Lie; Fu, Xiaojie

    2015-01-01

    Cistanches Herba (CH) is thought to be a “Yang-invigorating” material in traditional Chinese medicine. We evaluated neuroprotective effects of Cistanches Herba on Alzheimer's disease (AD) patients. Moderate AD participants were divided into 3 groups: Cistanches Herba capsule (CH, n = 10), Donepezil tablet (DON, n = 8), and control group without treatment (n = 6). We assessed efficacy by MMSE and ADAS-cog, and investigated the volume changes of hippocampus by 1.5 T MRI scans. Protein, mRNA levels, and secretions of total-tau (T-tau), tumor necrosis factor-α (TNF-α), and interleukin- (IL) 1β (IL-1β) in cerebrospinal fluid (CSF) were detected by Western blot, RT-PCR, and ELISA. The scores showed statistical difference after 48 weeks of treatment compared to control group. Meanwhile, volume changes of hippocampus were slight in drug treatment groups but distinct in control group; the levels of T-tau, TNF-α, and IL-1β were decreased compared to those in control group. Cistanches Herba could improve cognitive and independent living ability of moderate AD patients, slow down volume changes of hippocampus, and reduce the levels of T-tau, TNF-α, and IL-1β. It suggested that Cistanches Herba had potential neuroprotective effects for moderate AD. PMID:26435722

  5. Visuomotor integration is compromised in Alzheimer's disease patients reaching for remembered targets.

    PubMed

    Tippett, William J; Krajewski, Adam; Sergio, Lauren E

    2007-01-01

    This study examined the ability of neurologically healthy individuals and individuals with Alzheimer's disease (AD) to successfully complete procedures involving short-term spatial visuomotor memory tasks, and tasks involving increasingly complex visuomotor transformations. Participants made sliding finger movements over a clear touch-sensitive screen on two separate spatial planes (vertical and horizontal), to visually constant and remembered target positions. Significant main effects were observed between participant groups on reaction time and movement time measures. As well, significant changes in reaction time and movement time were observed within the patient group over the different of any experimental procedures. In addition, as task increased in complexity significant increases in errors were observed in the AD group. Overall, the results reveal that AD patients show substantial declines in their ability to process and integrate visual information to produce motor responses. Therefore, we believe that this psychophysical research provides further evidence that AD, even early stages of AD, can affect anatomical regions supporting vision for action.

  6. Causes of Alzheimer's disease

    PubMed Central

    Munoz, D G; Feldman, H

    2000-01-01

    It is now understood that genetic factors play a crucial role in the risk of developing Alzheimer's disease (AD). Rare mutations in at least 3 genes are responsible for early-onset familial AD. A common polymorphism in the apolipoprotein E gene is the major determinant of risk in families with late-onset AD, as well as in the general population. Advanced age, however, remains the major established risk factor for AD, although environmental variables may also have some role in disease expression. Some pathogenic factors directly associated with aging include oxidative damage and mutations in messenger RNA. Other factors unrelated to the aging process may, in the future, be amenable to therapeutic intervention by way of estrogen replacement therapy for postmenopausal women, anti-inflammatory drug therapy and reducing vascular risk factors. Older theories, such as aluminum playing a role in the pathogenesis of AD, have been mostly discarded as our understanding of pathogenic mechanisms of AD has advanced. PMID:11216203

  7. Characteristics of Agraphia in Chinese Patients with Alzheimer's Disease and Amnestic Mild Cognitive Impairment

    PubMed Central

    Zhou, Jiong; Jiang, Biao; Huang, Xian-Hong; Kong, Lin-Lin; Li, Hong-Lei

    2016-01-01

    Background: Patients with Alzheimer's disease (AD) manifest progressive decline in writing abilities. Most studies on agraphia in AD have been performed in the alphabetic system, such as English. However, these findings may not be applicable to other written language systems. The unique features of the Chinese written script could affect the patterns of agraphia in Chinese AD patients. The aim of this study was to explore the features of writing errors in Chinese patients with AD and amnestic mild cognitive impairment (a-MCI), as well as to study the relationship between their writing errors and neuropsychological functions. Methods: In this study, we performed an observational study in a group of subjects including 17 AD patients, 14 patients with a-MCI, and 16 elderly healthy controls. We analyzed the writing errors in these subjects and also studied the relationship between their writing errors and neuropsychological functions. Results: Our study showed that in patients whose mother tongue is Chinese, writing ability was comparatively well preserved in the MCI phase but significantly impaired when the disease progressed to the stage of AD. The writing errors showed corresponding increase with the severity of cognition decline, both in the types of errors and rate of occurrence. Analysis of the writing errors showed that word substitution and unintelligible words were the most frequent error types that occurred in all the three study groups. The occurrence rate of unintelligible words was significantly higher in the AD group compared with the a-MCI group (P = 0.024) and control group (P = 0.018). In addition, the occurrence rates of word substitution were also significantly higher in AD (P = 0.013) and a-MCI groups (P = 0.037) than that of control group. However, errors such as totally no response, visuospatial impairment, paragraph agraphia, ideograph, and perseverative writing errors were only seen in AD group. Besides, we also found a high occurrence rate of

  8. CSF markers in Alzheimer disease patients are not related to the different degree of cognitive impairment.

    PubMed

    Stefani, Alessandro; Martorana, Alessandro; Bernardini, Sergio; Panella, Marta; Mercati, Flavio; Orlacchio, Antonio; Pierantozzi, Mariangela

    2006-12-21

    Standard markers in cerebrospinal fluid (CSF), as soluble amyloid beta 1-42 (Abeta1-42) and total tau protein (t-tau), may contribute to dementia subtypes diagnostic accuracy. Yet, their sensitivity to assess the different degree of cognitive deficit is not fully clarified. Our study analyses Abeta1-42 and t-tau CSF levels in different cohorts of Alzheimer's disease (AD) patients, distinguished as early AD (mild cognitively impaired subjects recently converted to AD), mild AD (MMSE<23; > or =18), and moderately advanced AD (MMSE<18). The control group was represented by age-matched patients affected by depressive pseudo-dementia. Reduced Abeta1-42 and increased t-tau CSF levels were confirmed as hallmarks of AD at any disease stage. In early AD patients, Abeta1-42 levels were already significantly low, if compared to the control group (336 vs 867 ng/L; p<0.0001). On the contrary, Abeta1-42 levels did not differ between AD subgroups, and in particular between mild to moderate AD. A significant progressive increase of t-tau concentration was found when comparing early AD (269 ng/L) to more advanced AD stages (468 ng/L and 495 ng/L for mild and moderate AD, respectively). Our findings confirm that the impairment of amyloidogenic cascade is an early, even pre-clinical process, but suggest that soluble Abeta1-42 concentration has a negligible correlation with the clinical progression. Conversely, t-tau concentration correlates with the transition towards marked cognitive impairment.

  9. Correlation between hippocampal volumes and medial temporal lobe atrophy in patients with Alzheimer's disease

    PubMed Central

    Dhikav, Vikas; Duraiswamy, Sharmila; Anand, Kuljeet Singh

    2017-01-01

    Introduction: Hippocampus undergoes atrophy in patients with Alzheimer's disease (AD). Calculation of hippocampal volumes can be done by a variety of methods using T1-weighted images of magnetic resonance imaging (MRI) of the brain. Medial temporal lobes atrophy (MTL) can be rated visually using T1-weighted MRI brain images. The present study was done to see if any correlation existed between hippocampal volumes and visual rating scores of the MTL using Scheltens Visual Rating Method. Materials and Methods: We screened 84 subjects presented to the Department of Neurology of a Tertiary Care Hospital and enrolled forty subjects meeting the National Institute of Neurological and Communicative Disorders and Stroke, AD related Disease Association criteria. Selected patients underwent MRI brain and T1-weighted images in a plane perpendicular to long axis of hippocampus were obtained. Hippocampal volumes were calculated manually using a standard protocol. The calculated hippocampal volumes were correlated with Scheltens Visual Rating Method for Rating MTL. A total of 32 cognitively normal age-matched subjects were selected to see the same correlation in the healthy subjects as well. Sensitivity and specificity of both methods was calculated and compared. Results: There was an insignificant correlation between the hippocampal volumes and MTL rating scores in cognitively normal elderly (n = 32; Pearson Correlation coefficient = 0.16, P > 0.05). In the AD Group, there was a moderately strong correlation between measured hippocampal volumes and MTL Rating (Pearson's correlation coefficient = −0.54; P < 0.05. There was a moderately strong correlation between hippocampal volume and Mini-Mental Status Examination in the AD group. Manual delineation was superior compared to the visual method (P < 0.05). Conclusions: Good correlation was present between manual hippocampal volume measurements and MTL scores. Sensitivity and specificity of manual measurement of hippocampus was

  10. Plasma tau in Alzheimer disease

    PubMed Central

    Zetterberg, Henrik; Janelidze, Shorena; Insel, Philip S.; Andreasson, Ulf; Stomrud, Erik; Palmqvist, Sebastian; Baker, David; Tan Hehir, Cristina A.; Jeromin, Andreas; Hanlon, David; Song, Linan; Shaw, Leslie M.; Trojanowski, John Q.; Weiner, Michael W.; Hansson, Oskar; Blennow, Kaj

    2016-01-01

    Objective: To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. Methods: This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, 18fluorodeoxyglucose-PET, and cognition. Results: Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ42, but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up. Conclusions: Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD. PMID:27694257

  11. [Antibody therapy for Alzheimer's disease].

    PubMed

    Tabira, Takeshi; Matsumoto, Shin-Ei; Jin, Haifeng

    2011-11-01

    In order to avoid Abeta-induced autoimmune encephalitis, several monoclonal and polyclonal antibodies are in clinical trials. These are bapineuzumab, solanezumab, ponezumab, gantenerumab, BAN2401, gammaguard and octagam. Since each antibody has a different antigen epitope of Abeta, anti-amyloid activities are different. It is unknown which antibody is effective for Alzheimer disease, and we must wait for the result of clinical trials. Some patients who developed tissue amyloid plaque immuno-reactive (TAPIR) antibody showed slower decline after AN-1792 vaccination. We developed TAPIR-like monoclonal antibody, which was found to react with Abeta oligomers preferentially.

  12. Memory loss in Alzheimer's disease.

    PubMed

    Jahn, Holger

    2013-12-01

    Loss of memory is among the first symptoms reported by patients suffering from Alzheimer's disease (AD) and by their caretakers. Working memory and long-term declarative memory are affected early during the course of the disease. The individual pattern of impaired memory functions correlates with parameters of structural or functional brain integrity. AD pathology interferes with the formation of memories from the molecular level to the framework of neural networks. The investigation of AD memory loss helps to identify the involved neural structures, such as the default mode network, the influence of epigenetic and genetic factors, such as ApoE4 status, and evolutionary aspects of human cognition. Clinically, the analysis of memory assists the definition of AD subtypes, disease grading, and prognostic predictions. Despite new AD criteria that allow the earlier diagnosis of the disease by inclusion of biomarkers derived from cerebrospinal fluid or hippocampal volume analysis, neuropsychological testing remains at the core of AD diagnosis.

  13. Basal Forebrain Atrophy Contributes to Allocentric Navigation Impairment in Alzheimer's Disease Patients.

    PubMed

    Kerbler, Georg M; Nedelska, Zuzana; Fripp, Jurgen; Laczó, Jan; Vyhnalek, Martin; Lisý, Jiří; Hamlin, Adam S; Rose, Stephen; Hort, Jakub; Coulson, Elizabeth J

    2015-01-01

    The basal forebrain degenerates in Alzheimer's disease (AD) and this process is believed to contribute to the cognitive decline observed in AD patients. Impairment in spatial navigation is an early feature of the disease but whether basal forebrain dysfunction in AD is responsible for the impaired navigation skills of AD patients is not known. Our objective was to investigate the relationship between basal forebrain volume and performance in real space as well as computer-based navigation paradigms in an elderly cohort comprising cognitively normal controls, subjects with amnestic mild cognitive impairment and those with AD. We also tested whether basal forebrain volume could predict the participants' ability to perform allocentric- vs. egocentric-based navigation tasks. The basal forebrain volume was calculated from 1.5 T magnetic resonance imaging (MRI) scans, and navigation skills were assessed using the human analog of the Morris water maze employing allocentric, egocentric, and mixed allo/egocentric real space as well as computerized tests. When considering the entire sample, we found that basal forebrain volume correlated with spatial accuracy in allocentric (cued) and mixed allo/egocentric navigation tasks but not the egocentric (uncued) task, demonstrating an important role of the basal forebrain in mediating cue-based spatial navigation capacity. Regression analysis revealed that, although hippocampal volume reflected navigation performance across the entire sample, basal forebrain volume contributed to mixed allo/egocentric navigation performance in the AD group, whereas hippocampal volume did not. This suggests that atrophy of the basal forebrain contributes to aspects of navigation impairment in AD that are independent of hippocampal atrophy.

  14. Supporting autobiographical memory in patients with Alzheimer's disease using smart phones.

    PubMed

    De Leo, Gianluca; Brivio, Eleonora; Sautter, Scott W

    2011-01-01

    An estimated 5.1 million Americans suffer from Alzheimer's disease (AD). A symptom of AD is the gradual loss of autobiographical memory. Support services have been shown to slow such loss, thereby improving the quality of life of patients and their caregivers. In this case study, a subject in Stage 4 of AD on the Functional Assessment Staging (FAST) scale carried a smart phone with a lanyard for 4 weeks. The smart phone was programmed to take pictures at 5-minute intervals for 12 hours during the day. The pictures were collected, combined in a video slide show, saved to a DVD, and mailed to the subject on a weekly basis. The subject and his caregiver had to view the DVD. In order to evaluate the subject's memory before and after viewing the DVD, a test concerning the most important events of the week was developed. The subject and his caregiver had to answer a satisfaction questionnaire as well. The results of this case study confirmed that the DVD helped the subject recall recent events significantly better and that carrying the smart phone was not considered intrusive to daily routines. This manuscript illustrates how smart phone technology can assist in exercising autobiographical memory.

  15. Pericellular innervation of neurons expressing abnormally hyperphosphorylated tau in the hippocampal formation of Alzheimer's disease patients.

    PubMed

    Blazquez-Llorca, Lidia; Garcia-Marin, Virginia; Defelipe, Javier

    2010-01-01

    Neurofibrillary tangles (NFT) represent one of the main neuropathological features in the cerebral cortex associated with Alzheimer's disease (AD). This neurofibrillary lesion involves the accumulation of abnormally hyperphosphorylated or abnormally phosphorylated microtubule-associated protein tau into paired helical filaments (PHF-tau) within neurons. We have used immunocytochemical techniques and confocal microscopy reconstructions to examine the distribution of PHF-tau-immunoreactive (ir) cells, and their perisomatic GABAergic and glutamatergic innervations in the hippocampal formation and adjacent cortex of AD patients. Furthermore, correlative light and electron microscopy was employed to examine these neurons and the perisomatic synapses. We observed two patterns of staining in PHF-tau-ir neurons, pattern I (without NFT) and pattern II (with NFT), the distribution of which varies according to the cortical layer and area. Furthermore, the distribution of both GABAergic and glutamatergic terminals around the soma and proximal processes of PHF-tau-ir neurons does not seem to be altered as it is indistinguishable from both control cases and from adjacent neurons that did not contain PHF-tau. At the electron microscope level, a normal looking neuropil with typical symmetric and asymmetric synapses was observed around PHF-tau-ir neurons. These observations suggest that the synaptic connectivity around the perisomatic region of these PHF-tau-ir neurons was apparently unaltered.

  16. Pericellular Innervation of Neurons Expressing Abnormally Hyperphosphorylated Tau in the Hippocampal Formation of Alzheimer's Disease Patients

    PubMed Central

    Blazquez-Llorca, Lidia; Garcia-Marin, Virginia; DeFelipe, Javier

    2010-01-01

    Neurofibrillary tangles (NFT) represent one of the main neuropathological features in the cerebral cortex associated with Alzheimer's disease (AD). This neurofibrillary lesion involves the accumulation of abnormally hyperphosphorylated or abnormally phosphorylated microtubule-associated protein tau into paired helical filaments (PHF-tau) within neurons. We have used immunocytochemical techniques and confocal microscopy reconstructions to examine the distribution of PHF-tau-immunoreactive (ir) cells, and their perisomatic GABAergic and glutamatergic innervations in the hippocampal formation and adjacent cortex of AD patients. Furthermore, correlative light and electron microscopy was employed to examine these neurons and the perisomatic synapses. We observed two patterns of staining in PHF-tau-ir neurons, pattern I (without NFT) and pattern II (with NFT), the distribution of which varies according to the cortical layer and area. Furthermore, the distribution of both GABAergic and glutamatergic terminals around the soma and proximal processes of PHF-tau-ir neurons does not seem to be altered as it is indistinguishable from both control cases and from adjacent neurons that did not contain PHF-tau. At the electron microscope level, a normal looking neuropil with typical symmetric and asymmetric synapses was observed around PHF-tau-ir neurons. These observations suggest that the synaptic connectivity around the perisomatic region of these PHF-tau-ir neurons was apparently unaltered. PMID:20631843

  17. A Yoga and Compassion Meditation Program Reduces Stress in Familial Caregivers of Alzheimer's Disease Patients

    PubMed Central

    Danucalov, M. A. D.; Kozasa, E. H.; Ribas, K. T.; Galduróz, J. C. F.; Garcia, M. C.; Verreschi, I. T. N.; Oliveira, K. C.; Romani de Oliveira, L.; Leite, J. R.

    2013-01-01

    Familial caregivers of patients with Alzheimer's disease exhibit reduced quality of life and increased stress levels. The aim of this study was to investigate the effects of an 8-week yoga and compassion meditation program on the perceived stress, anxiety, depression, and salivary cortisol levels in familial caregivers. A total of 46 volunteers were randomly assigned to participate in a stress-reduction program for a 2-month period (yoga and compassion meditation program—YCMP group) (n = 25) or an untreated group for the same period of time (control group) (n = 21). The levels of stress, anxiety, depression, and morning salivary cortisol of the participants were measured before and after intervention. The groups were initially homogeneous; however, after intervention, the groups diverged significantly. The YCMP group exhibited a reduction of the stress (P < 0.05), anxiety (P < 0.000001), and depression (P < 0.00001) levels, as well as a reduction in the concentration of salivary cortisol (P < 0.05). Our study suggests that an 8-week yoga and compassion meditation program may offer an effective intervention for reducing perceived stress, anxiety, depression, and salivary cortisol in familial caregivers. PMID:23690846

  18. Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients.

    PubMed

    Damjanovic, Amanda K; Yang, Yinhua; Glaser, Ronald; Kiecolt-Glaser, Janice K; Nguyen, Huy; Laskowski, Bryon; Zou, Yixiao; Beversdorf, David Q; Weng, Nan-ping

    2007-09-15

    Caregivers of Alzheimer's disease patients endure chronic stress associated with a decline of immune function. To assess the psychological and immunological changes of caregivers, we compared depressive symptoms, PBMC composition, in vitro activation-induced proliferation and cytokine production, and telomere length and telomerase activity of 82 individuals (41 caregivers and 41 age- and gender-matched controls). We found depressive symptoms were significantly higher in caregivers than in controls (p < 0.001). Correspondingly, caregivers had significantly lower T cell proliferation but higher production of immune-regulatory cytokines (TNF-alpha and IL-10) than controls in response to stimulation in vitro. We examined the impact of these changes on cellular replicative lifespan and found that caregivers had significantly shorter telomere lengths in PBMC than controls (6.2 and 6.4 kb, respectively, p < 0.05) with similar shortening in isolated T cells and monocytes and that this telomere attrition in caregivers was not due to an increase of shorter telomere possessing T cell subsets in PBMC. Finally, we showed that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls (p < 0.0001), pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers. These findings demonstrate that chronic stress is associated with altered T cell function and accelerated immune cell aging as suggested by excessive telomere loss.

  19. Metals and Alzheimer's disease.

    PubMed

    Adlard, Paul A; Bush, Ashley I

    2006-11-01

    There is increasing evidence to support a role for both the amyloid beta-protein precursor (AbetaPP) and its proteolytic fragment, amyloid beta (Abeta), in metal ion homeostasis. Furthermore, metal ions such as zinc and copper can interact with both AbetaPP and Abeta to potentiate Alzheimer's disease by participating in the aggregation of these normal cellular proteins and in the generation of reactive oxygen species. In addition, metal ions may interact on several other AD-related pathways, including those involved in neurofibrillary tangle formation, secretase cleavage of AbetaPP and proteolytic degradation of Abeta. As such, a dysregulation of metal ion homeostasis, as occurs with both aging and in AD, may foster an environment that can both precipitate and accelerate degenerative conditions such as AD. This offers a broad biochemical front for novel therapeutic interventions.

  20. Possibility of Acetylcholinesterase Overexpression in Alzheimer Disease Patients after Therapy with Acetylcholinesterase Inhibitors.

    PubMed

    Kračmarová, Alžběta; Drtinová, Lucie; Pohanka, Miroslav

    2015-01-01

    Acetylcholinesterase is an enzyme responsible for termination of excitatory transmission at cholinergic synapses by the hydrolyzing of a neurotransmitter acetylcholine. Nowadays, other functions of acetylcholinesterase in the organism are considered, for example its role in regulation of apoptosis. Cholinergic nervous system as well as acetylcholinesterase activity is closely related to pathogenesis of Alzheimer disease. The mostly used therapy of Alzheimer disease is based on enhancing cholinergic function using inhibitors of acetylcholinesterase like rivastigmine, donepezil or galantamine. These drugs can influence not only the acetylcholinesterase activity but also other processes in treated organism. The paper is aimed mainly on possibility of increased expression and protein level of acetylcholinesterase caused by the therapy with acetylcholinesterase inhibitors.

  1. Verbal fluency in Alzheimer's disease, Parkinson's disease, and major depression

    PubMed Central

    de Araujo, Narahyana Bom; Barca, Maria Lage; Engedal, Knut; Coutinho, Evandro Silva Freire; Deslandes, Andrea Camaz; Laks, Jerson

    2011-01-01

    OBJECTIVE: To compare verbal fluency among Alzheimer's disease, Parkinson's disease, and major depression and to assess the sociodemographic and clinical factors associated with the disease severity. METHODS: Patients from an outpatient university center with a clinical diagnosis of Alzheimer's disease, Parkinson's disease or major depression were studied. Severity was staged using the Hoehn & Yahr scale, the Hamilton Depression scale and the Clinical Dementia Rating for Parkinson's disease, major depression, and Alzheimer's disease, respectively. All subjects were tested with the Mini-Mental State Examination, the digit span test, and the verbal fluency test (animals). We fit four types of regression models for the count variable: Poisson model, negative binomial model, zero-inflated Poisson model, and zero-inflated negative binomial model. RESULTS: The mean digit span and verbal fluency scores were lower in patients with Alzheimer's disease (n = 34) than in patients with major depression (n = 52) or Parkinson's disease (n = 17) (p<0.001). The average number of words listed was much lower for Alzheimer's disease patients (7.2 words) compared to the patients presenting with major depression (14.6 words) or Parkinson's disease (15.7 words) (KW test = 32.4; p<0.01). Major depression and Parkinson's disease groups listed 44% (ROM = 1.44) and 48% (ROM = 1.48) more words, respectively, compared to those patients with Alzheimer's disease; these results were independent of age, education, disease severity and attention. Independently of diagnosis, age, and education, severe disease showed a 26% (ROM = 0.74) reduction in the number of words listed when compared to mild cases. CONCLUSIONS: Verbal fluency provides a better characterization of Alzheimer's disease, major depression, and Parkinson's disease, even at later stages. PMID:21655757

  2. Microwaves and Alzheimer's disease

    PubMed Central

    Zhang, Xia; Huang, Wen-Juan; Chen, Wei-Wei

    2016-01-01

    Alzheimer's diseases (AD) is the most common type of dementia and a neurodegenerative disease that occurs when the nerve cells in the brain die. The cause and treatment of AD remain unknown. However, AD is a disease that affects the brain, an organ that controls behavior. Accordingly, anything that can interact with the brain may affect this organ positively or negatively, thereby protecting or encouraging AD. In this regard, modern life encompasses microwaves for all issues including industrial, communications, medical and domestic tenders, and among all applications, the cell phone wave, which directly exposes the brain, continues to be the most used. Evidence suggests that microwaves may produce various biological effects on the central nervous system (CNS) and many arguments relay the possibility that microwaves may be involved in the pathophysiology of CNS disease, including AD. By contrast, previous studies have reported some beneficial cognitive effects and that microwaves may protect against cognitive impairment in AD. However, although many of the beneficial effects of microwaves are derived from animal models, but can easily be extrapolated to humans, whether microwaves cause AD is an important issue that is to be addressed in the current review. PMID:27698682

  3. Microwaves and Alzheimer's disease.

    PubMed

    Zhang, Xia; Huang, Wen-Juan; Chen, Wei-Wei

    2016-10-01

    Alzheimer's diseases (AD) is the most common type of dementia and a neurodegenerative disease that occurs when the nerve cells in the brain die. The cause and treatment of AD remain unknown. However, AD is a disease that affects the brain, an organ that controls behavior. Accordingly, anything that can interact with the brain may affect this organ positively or negatively, thereby protecting or encouraging AD. In this regard, modern life encompasses microwaves for all issues including industrial, communications, medical and domestic tenders, and among all applications, the cell phone wave, which directly exposes the brain, continues to be the most used. Evidence suggests that microwaves may produce various biological effects on the central nervous system (CNS) and many arguments relay the possibility that microwaves may be involved in the pathophysiology of CNS disease, including AD. By contrast, previous studies have reported some beneficial cognitive effects and that microwaves may protect against cognitive impairment in AD. However, although many of the beneficial effects of microwaves are derived from animal models, but can easily be extrapolated to humans, whether microwaves cause AD is an important issue that is to be addressed in the current review.

  4. Early Alzheimer's disease genetics.

    PubMed

    Schellenberg, Gerard D

    2006-01-01

    The genetics community working on Alzheimer's disease and related dementias has made remarkable progress in the past 20 years. The cumulative efforts by multiple groups have lead to the identification of three autosomal dominant genes for early onset AD. These are the amyloid-beta protein precursor gene (APP), and the genes encoding presenilin1 and 2. The knowledge derived from this work has firmly established Abeta as a critical disease molecule and lead to candidate drugs currently in treatment trials. Work on a related disease, frontotemporal dementia with parkinsonism - chromosome 17 type has also added to our understanding of pathogenesis by revealing that tau, the protein component of neurofibrillary tangles, is also a critical molecule in neurodegeneration. Lessons learned that still influence work on human genetics include the need to recognize and deal with genetic heterogeneity, a feature common to many genetic disorders. Genetic heterogeneity, if recognized, can be source of information. Another critical lesson is that clinical, molecular, and statistical scientists need to work closely on disease projects to succeed in solving the complex problems of common genetic disorders.

  5. The "hidden" semantic category dissociation in mild-moderate Alzheimer's disease patients.

    PubMed

    Albanese, Emiliano

    2007-03-02

    In patients manifesting mild-moderate Alzheimer's disease (AD), lexical semantic tasks are known to be influenced by several variables which should be adequately taken into account when studying semantic category dissociations. The following study provides indexes of three new variables (imageability (I), percentage of name agreement (pNA) and number of target alternatives (nTA)) and investigates their role in naming in a group of people with AD and in matched older adults controls. Forty young healthy participants rated I, pNA and nTA of 155 stimuli (including living and non-living items) from and sets. Forty-eight people with mild-moderate AD and 40 older adults were given the two naming tests and their naming ratings were analysed with a two-way ANOVA (two groupsxtwo categories) to assess category specificity and the effect of interaction. The influence of relevant concomitant variables in naming was measured using a multiple regression analysis. Semi-partial correlations were carried out to assess the independent contribution of each variable to naming. We found that living items were more imageable and had fewer lexical alternatives and higher name agreement than non-living items. We also found that controls significantly named better than AD patients (F=37.551, p<.001), whilst the two-way ANOVA showed no significant effect of category (F=.649, p=.423). Notably category effect emerged when assessing its independent contribution performing a semi-partial correlation (beta=-.278, p<.001) which kept the effect of relevant concomitant variables under control. Our results confirm that category dissociation does emerge in mild-moderate AD patients when the effect of relevant concomitant variables is adequately taken into account. The hypothesis that the highly correlated properties of items from biological categories may play a protective effect on living things, making them less prone to impairment in the early stages of AD, is discussed.

  6. Does retrieval frequency account for the pattern of autobiographical memory loss in early Alzheimer's disease patients?

    PubMed

    De Simone, Maria Stefania; Fadda, Lucia; Perri, Roberta; Aloisi, Marta; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

    2016-01-08

    Episodic autobiographical memory (ABM) has been found to be impaired from the early stage of Alzheimer's disease (AD). Previous works have focused on how ABM decreases over the lifespan, but no study has deeply investigated whether the extent of episodic autobiographical amnesia is mediated by the retrieval frequency of the episodic trace itself. The aim of the present study was to determine whether the frequency of trace retrieval has an effect on the quality of autobiographical incidents recall and whether the extent of this contribution changes over time. For this purpose, the episodic component of ABM was assessed in patients in the early stage of AD through a questionnaire which allowed evaluating memory of past personal incidents as a function of both their age of acquisition and retrieval frequency. We found that both AD patients and healthy controls took advantage of greater retrieval frequency across all time segments, because of their better memory performance on frequently retrieved episodes than less frequently retrieved ones. Although in the AD group the retrieval frequency effect (i.e., higher scores on the episodes rated as more frequently retrieved) was found in all time segments, the extent of its beneficial effect on memory performance was temporally-graded and inversely related to the time course. Our findings provide new evidence that the combined action of both age of memory and retrieval frequency could provide a valuable framework for predicting patterns of ABM loss, at least in early AD patients. In line with the Multiple Trace Theory, we speculated that retrieval frequency protects episodic trace recall against hippocampal damage by reinforcing the neural representation of personal context-rich memories, which consequently are easier to access and recall. Furthermore, the age of memory should change the amplitude of this beneficial effect as a function of the remoteness of the trace.

  7. Advancing frontiers in Alzheimer's disease research

    SciTech Connect

    Glenner, G.G.; Wurtman, R.J.

    1987-01-01

    This book contain 16 chapters. Some of the titles are: Transmitter Alterations in Alzheimer's Disease: Relation to Cortical Dysfunction as Suggested by Positron Emission Tomography; Single-Photon Emission Computed Tomography in the Clinical Evaluation of Dementia; Clinical Diagnosis of Alzheimer's Disease; Down's Syndrome and Alzheimer's Disease: What is the Relationship; and Beta Protein: A Possible Marker for Alzheimer's Disease.

  8. Useful Information on...Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Cohen, Gene D.

    This brochure provides information on Alzheimer's disease by examining who gets Alzheimer's disease and what to expect when someone has Alzheimer's disease. Abnormal brain tissue findings are discussed and three clinical features of Alzheimer's disease are listed: dementia; insidious onset of symptoms; and exclusion of all other specific causes of…

  9. Health-Related Quality of Life in Patients with Alzheimer's Disease in Different German Health Care Settings.

    PubMed

    Heßmann, Philipp; Seeberg, Greta; Reese, Jens Peter; Dams, Judith; Baum, Erika; Müller, Matthias J; Dodel, Richard; Balzer-Geldsetzer, Monika

    2016-01-01

    The purpose of this study is to evaluate the health-related quality of life (HrQoL) of patients with Alzheimer's disease (AD) in different care settings (institutionalized versus community-dwelling) across all severity stages of dementia. Patients were consecutively recruited with their primary caregivers (123 inpatients and 272 outpatients), and the impact of patient-related parameters such as behavioral and psychological symptoms of dementia (BPSD) (Geriatric Depression Scale [GDS] and Neuropsychiatric Inventory [NPI]) and functional capacity (Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL]) on HrQoL was analyzed. Patients' HrQoL was assessed using self-reported and caregiver-rated generic (EuroQoL Instrument) and dementia-specific (Quality of Life-Alzheimer's Disease [Qol-AD]) scales. Patients reported a considerably higher HrQoL than their caregivers on the QoL-AD, EQ-5D, and EQ VAS (p <  0.001). Different dementia severity groups showed significantly worse results in HrQoL for patients with lower MMSE scores. The mean self-reported QoL-AD decreased from 32.3±5.7 in the group with the highest MMSE scores to 27.1±5.5 in patients with the lowest MMSE scores (p <  0.001). A considerably lower HrQoL was shown for institutionalized patients versus participants in outpatient settings (proxy-rated QoL-AD 19.7±4.6 versus 26.0±7.1, p <  0.001). Depressive symptoms (GDS), BPSD (NPI), and reduced functional capacity (ADCS-ADL) were evaluated for their impact on patients' HrQoL. Multivariate models explained between 22% and 54% of the variance in patients' HrQoL. To analyze the causative direction of the reported associations, further longitudinal studies should be conducted.

  10. Altered phosphorylation of. tau. protein in heat-shocked rats and patients with Alzheimer disease

    SciTech Connect

    Papasozomenos, S.C.; Yuan Su Baylor College of Medicine, Houston, TX )

    1991-05-15

    Six hours after heat shocking 2- to 3-month-old male and female Sprague-Dawley rats at 42C for 15 min, the authors analyzed {tau} protein immunoreactivity in SDS extracts of cerebrums and peripheral nerves by using immunoblot analysis and immunohistochemistry with the anti-{tau} monoclonal antibody Tau-1, which recognizes a phosphate-dependent nonphosphorylated epitope, and with {sup 125}I-labeled protein A. In the cerebal extracts, the authors found altered phosphorylation of {tau} in heat-shocked females, characterized by a marked reduction in the amount of nonphosphorylated {tau}, a doubling of the ratio of total (phosphorylated plus nonphosphorylated) {tau} to nonphosphorylated {tau}, and the appearance of the slowest moving phosphorylated {tau} polypeptide (68 kDa). Similar, but milder, changes were observed in male rats. Quantitative immunoblot analysis of cortex and the underlying white matter with Tau-1 and {sup 125}I-labeled protein A showed that the amount of phosphorylated {tau} progressively increased in the Alzheimer disease-affected cerebral cortex, while concurrently a proportionally lesser amount of {tau} entered the white matter axons. The similar findings for the rat heat-shock model and Alzheimer disease suggest that life stressors may play a role in the etiopathogenesis of Alzheimer's disease.

  11. Molecular imaging of Alzheimer disease pathology.

    PubMed

    Kantarci, K

    2014-06-01

    Development of molecular imaging agents for fibrillar β-amyloid positron-emission tomography during the past decade has brought molecular imaging of Alzheimer disease pathology into the spotlight. Large cohort studies with longitudinal follow-up in cognitively normal individuals and patients with mild cognitive impairment and Alzheimer disease indicate that β-amyloid deposition can be detected many years before the onset of symptoms with molecular imaging, and its progression can be followed longitudinally. The utility of β-amyloid PET in the differential diagnosis of Alzheimer disease is greatest when there is no pathologic overlap between 2 dementia syndromes, such as in frontotemporal lobar degeneration and Alzheimer disease. However β-amyloid PET alone may be insufficient in distinguishing dementia syndromes that commonly have overlapping β-amyloid pathology, such as dementia with Lewy bodies and vascular dementia, which represent the 2 most common dementia pathologies after Alzheimer disease. The role of molecular imaging in Alzheimer disease clinical trials is growing rapidly, especially in an era when preventive interventions are designed to eradicate the pathology targeted by molecular imaging agents.

  12. Brain imaging in Alzheimer disease.

    PubMed

    Johnson, Keith A; Fox, Nick C; Sperling, Reisa A; Klunk, William E

    2012-04-01

    Imaging has played a variety of roles in the study of Alzheimer disease (AD) over the past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes of dementia. More recently, a variety of imaging modalities including structural and functional MRI and positron emission tomography (PET) studies of cerebral metabolism with fluoro-deoxy-d-glucose (FDG) and amyloid tracers such as Pittsburgh Compound-B (PiB) have shown characteristic changes in the brains of patients with AD, and in prodromal and even presymptomatic states that can help rule-in the AD pathophysiological process. No one imaging modality can serve all purposes as each have unique strengths and weaknesses. These modalities and their particular utilities are discussed in this article. The challenge for the future will be to combine imaging biomarkers to most efficiently facilitate diagnosis, disease staging, and, most importantly, development of effective disease-modifying therapies.

  13. A prospective study of nutrition education and oral nutritional supplementation in patients with Alzheimer's disease

    PubMed Central

    2011-01-01

    Background Weight loss in patients with Alzheimer's disease (AD) is a common clinical manifestation that may have clinical significance. Objectives To evaluate if there is a difference between nutrition education and oral nutritional supplementation on nutritional status in patients with AD. Methods A randomized, prospective 6-month study which enrolled 90 subjects with probable AD aged 65 years or older divided into 3 groups: Control Group (CG) [n = 27], Education Group (EG) [n = 25], which participated in an education program and Supplementation Group (SG) [n = 26], which received two daily servings of oral nutritional supplementation. Subjects were assessed for anthropometric data (weight, height, BMI, TSF, AC and AMC), biochemical data (total protein, albumin, and total lymphocyte count), CDR (Clinical Dementia Rating), MMSE (Mini-mental state examination), as well as dependence during meals. Results The SG showed a significant improvement in the following anthropometric measurements: weight (H calc = 22.12, p =< 0.001), BMI (H calc = 22.12, p =< 0.001), AC (H calc = 12.99, p =< 0.002), and AMC (H calc = 8.67, p =< 0.013) compared to the CG and EG. BMI of the EG was significantly greater compared to the CG. There were significant changes in total protein (H calc = 6.17, p =< 0.046), and total lymphocyte count in the SG compared to the other groups (H cal = 7.94, p = 0.019). Conclusion Oral nutritional supplementation is more effective compared to nutrition education in improving nutritional status. PMID:21943331

  14. Nanotechnology for Alzheimer Disease.

    PubMed

    Leszek, Jerzy; Tse, Wai Hei; Zhang, Jin; Ávila-Rodriguez, Marco Fidel; Tarasov, Vadim V; Barreto, George E; Bachurin, Sergey O; Aliev, Gjumrakch

    2017-02-03

    Dementia of Alzheimer disease (AD) type affects memory, thinking and behavior. Researchers believe that changes in the brain may begin 10-20 years before symptoms appear and AD is diagnosed. The need to diagnose and treat the devastating disease at an early stage is critical to manage and treat AD. Unfortunately, the lack of validated biomarkers limits the possibility of the earlier stages of AD. The advance of nanotechnology could offer huge opportunities in early-stage diagnosis and well treatment of AD. Biocompatible nanoparticles with diameter in the range of 1-100 nm could be used as targeted delivery system for drugs (e.g. Rivastigmine) to overcome the blood-brain barrier (BBB), and to minimize the side effects caused by over-dosage. In addition, biocompatible nanomaterials with enhanced optical and magnetic properties may allow them being excellent alternative contrast agents for early-stage diagnosis. With more studies on using nanomaterials and nanotechnology in complex biochemical environment of the central nervous system, it is most likely that nanomaterials and nanotechnology can be give significant impact on the early-stage diagnosis and treatment of AD. In this review we discuss the challenges of current treatment and diagnosis of AD and the development on biocompatible nanoparticles, and provide the rational and potentials of using nanoparticles for both drug carrier and imaging contrast agent for diagnosis and treatment of AD. .

  15. Neurogenesis in Alzheimer's disease

    PubMed Central

    Rodríguez, José J; Verkhratsky, Alexei

    2011-01-01

    It is widely acknowledged that neural stem cells generate new neurons through the process of neurogenesis in the adult brain. In mammals, adult neurogenesis occurs in two areas of the CNS: the subventricular zone and the subgranular zone of the dentate gyrus of the hippocampus. The newly generated cells display neuronal morphology, generate action potentials and receive functional synaptic inputs, their properties being equivalent to those of mature neurons. Alzheimer's disease (AD) is the widespread cause of dementia, and is an age-related, progressive and irreversible neurodegenerative disease that results in massive neuronal death and deterioration of cognitive functions. Here, we overview the relations between adult neurogenesis and AD, and try to analyse the controversies in the field. We also summarise recent data obtained in the triple transgenic model of AD that show time- and region-specific impairment of neurogenesis, which may account for the early changes in synaptic plasticity and cognitive impairments that develop prior to gross neurodegenerative alterations and that could underlie new rescue therapies. PMID:21323664

  16. Epigenomics of Alzheimer's disease.

    PubMed

    Bennett, David A; Yu, Lei; Yang, Jingyun; Srivastava, Gyan P; Aubin, Cristin; De Jager, Philip L

    2015-01-01

    Alzheimer's disease (AD) is a large and growing public health problem. It is characterized by the accumulation of amyloid β peptides and abnormally phosphorylated tau proteins that are associated with cognitive decline and dementia. Much has been learned about the genomics of AD from linkage analyses and, more recently, genome-wide association studies. Several but not all aspects of the genomic landscape are involved in amyloid β metabolism. The moderate concordance of disease among twins suggests other factors, potentially epigenomic factors, are related to AD. We are at the earliest stages of examining the relation of the epigenome to the clinical and pathologic phenotypes that characterize AD. Our literature review suggests that there is some evidence of age-related changes in human brain methylation. Unfortunately, studies of AD have been relatively small with limited coverage of methylation sites and microRNA, let alone other epigenomic marks. We are in the midst of 2 large studies of human brains including coverage of more than 420,000 autosomal cytosine-guanine dinucleotides with the Illumina Infinium HumanMethylation450 BeadArray, and histone acetylation with chromatin immunoprecipitation sequencing. We present descriptive data to help inform other researchers what to expect from these approaches to better design and power their studies. We then discuss future directions to inform on the epigenomic architecture of AD.

  17. Neuronutrition and Alzheimer's Disease

    PubMed Central

    Ramesh, Balenahalli N.; Rao, T.S. Sathyanarayana; Prakasam, Annamalai; Sambamurti, Kumar; Rao, K.S. Jagannatha

    2010-01-01

    Alzheimer's disease (AD) is a complex neurological disorder with several unequivocally identified genetic risk factors. Among the several environmental factors proposed for AD, dietary protective and risk factors have been most compelling. In particular, diets rich in saturated fatty acids and alcohol, and deficient in antioxidants and vitamins appear to promote the onset of the disease, while diets rich in unsaturated fatty acids, vitamins, antioxidants, and wine likely suppress its onset. Evidence suggests that diets rich in polyphenols and some spices suppress the onset of AD by scavenging free radicals and preventing oxidative damage. Metal ions are known to catalyze the production of free radicals and induce mental retardation or dementia. Several studies have also identified metals such as Pb, Fe, Al, Cu and Zn in AD pathogenesis. While specific chelators have been tested for therapy, they have not been very successful probably due to late administration after brain damage has been triggered. Since several dietary polyphenols are known to chelate metals, their routine use may also be protective against the onset of AD. PMID:20308778

  18. Neuroinhibitory molecules in Alzheimer's disease.

    PubMed

    Larner, A J; Keynes, R J

    2006-09-01

    Aberrant neurite growth is one of the neuropathological signatures of the Alzheimer's disease brain, both around amyloid plaques and in the cortical neuropil. Disruption of neuroinhibitory or repulsive growth and guidance signals, as well as of neurotrophic or permissive signals, may contribute to this dystrophic growth. Hence, therapeutic efforts directed exclusively at restoring neurotrophic activity are unlikely to meet with success. The molecular species responsible for neuroinhibitory effects in the Alzheimer's disease brain are beginning to be elucidated.

  19. Is knowledge of famous people disproportionately impaired in patients with early and questionable Alzheimer's disease?

    PubMed

    Thompson, Sian A; Graham, Kim S; Patterson, Karalyn; Sahakian, Barbara J; Hodges, John R

    2002-07-01

    Twenty-two patients with early dementia of Alzheimer's type (DAT) and 31 controls were administered tests of person-specific semantics (Experiment 1). DAT patients were impaired on all test components. In Experiment 2, 31 DAT patients, 28 questionable DAT (QDAT) patients, and 42 controls were administered the Graded Naming Test (GNT) and the newly designed Graded Faces Test (GFT), matched for difficulty with the GNT. DAT patients were impaired throughout but showed an advantage for naming objects over faces. The QDAT patients were impaired on the GFT only. Of the 7 QDAT patients who evolved to DAT within 1-2 years, 6 showed initial impairment on the GFT, whereas 17 of the nonconverters scored normally on the GFT. Results suggest greater and earlier vulnerability of person knowledge than general semantic knowledge in DAT.

  20. Quiz: Alzheimer's Disease Quiz | Alzheimer's disease | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Alzheimer's Disease Quiz: Alzheimer's Disease Quiz Past Issues / Fall 2010 Table of Contents How many people in the United States have Alzheimer's disease? as many as 5.1 million as many ...

  1. Biomarkers for early detection of Alzheimer disease.

    PubMed

    Barber, Robert C

    2010-09-01

    The existence of an effective biomarker for early detection of Alzheimer disease would facilitate improved diagnosis and stimulate therapeutic trials. Multidisciplinary clinical diagnosis of Alzheimer disease is time consuming and expensive and relies on experts who are rarely available outside of specialty clinics. Thus, many patients do not receive proper diagnosis until the disease has progressed beyond stages in which treatments are maximally effective. In the clinical trial setting, rapid, cost-effective screening of patients for Alzheimer disease is of paramount importance for the development of new treatments. Neuroimaging of cortical amyloid burden and volumetric changes in the brain and assessment of protein concentrations (eg, β-amyloid 1-42, total tau, phosphorylated tau) in cerebrospinal fluid are diagnostic tools that are not widely available. Known genetic markers do not provide sufficient discriminatory power between different forms of dementia to be useful in isolation. Recent studies using panels of biomarkers for diagnosis of Alzheimer disease or mild cognitive impairment have been promising, though no such studies have been cross-validated in independent samples of subjects. The ideal biomarker enabling early detection of Alzheimer disease has not yet been identified.

  2. Gene promoter methylation and expression of Pin1 differ between patients with frontotemporal dementia and Alzheimer's disease.

    PubMed

    Ferri, Evelyn; Arosio, Beatrice; D'Addario, Claudio; Galimberti, Daniela; Gussago, Cristina; Pucci, Mariangela; Casati, Martina; Fenoglio, Chiara; Abbate, Carlo; Rossi, Paolo Dionigi; Scarpini, Elio; Maccarrone, Mauro; Mari, Daniela

    2016-03-15

    Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD) share the accumulation of fibrillar aggregates of misfolded proteins. To better understand these neurodegenerative diseases and identify biomarkers in easily accessible cells, we investigated DNA methylation at Pin1 gene promoter and its expression in peripheral blood mononuclear cells of FTD patients. We found a lower gene expression of Pin1 with a higher DNA methylation in three CpG sites at Pin1 gene promoter analysed in FTD subjects, in contrast to a higher gene expression with a lower methylation in AD subjects and controls. These data suggest an important and distinct involvement of Pin1 in these two types of dementia.

  3. Cholinesterase inhibitors modulate autonomic function in patients with Alzheimer´s disease and mixed dementia.

    PubMed

    da Costa Dias, Filipi Leles; Ferreira Lisboa da Silva, Rose Mary; de Moraes, Edgar Nunes; Caramelli, Paulo

    2013-06-01

    Cholinesterase inhibitors (ChEIs), the mainstay treatment for dementia, have systemic actions that can affect cardiovascular and autonomic nervous system (ANS). Thirty-nine patients with Alzheimer´s disease or mixed dementia underwent a comprehensive clinical evaluation, prior to and during ChEIs therapy, including orthostatic challenge, electrocardiogram (EKG) and heart rate variability (HRV) spectral analysis through Holter recordings. ChEIs therapy determined a decrease in supine diastolic blood pressure (BP) and in both diastolic and systolic BP in orthostatic position (79.8 ± 9.0 vs. 76.4 ± 9.3 mmHg, p=0.012; 79.9 ± 11.6 vs. 75.3 ± 9.9, p=0.005 and 144.6 ± 25.8 vs. 137.6 ± 21.1, p=0.020, respectively). Spectral analysis revealed no difference on static HRV components, but, during orthostatic challenge, an increase in LF/HF ratio (2.2±2.4 vs. 4.6±5.9, p=0.011) and a reduction in HF component emerged (1604.3 ± 5610.1 vs. 266.1 ± 525.5, p=0.010). ChEIs showed no influence on EKG parameters or on the occurrence of orthostatic hypotension. Treatment with ChEIs was associated with functional improvement of the ANS behavior and to a decrease in supine DBP and in both orthostatic SBP and DBP.

  4. Does Caffeine Consumption Modify Cerebrospinal Fluid Amyloid-β Levels in Patients with Alzheimer's Disease?

    PubMed

    Travassos, Maria; Santana, Isabel; Baldeiras, Inês; Tsolaki, Magda; Gkatzima, Olymbia; Sermin, Genc; Yener, Görsev G; Simonsen, Anja; Hasselbalch, Steen G; Kapaki, Elisabeth; Mara, Bourbouli; Cunha, Rodrigo A; Agostinho, Paula; Blennow, Kaj; Zetterberg, Henrik; Mendes, Vera M; Manadas, Bruno; de Mendon, Alexandreça

    2015-01-01

    Caffeine may be protective against Alzheimer's disease (AD) by modulating amyloid-β (Aβ) metabolic pathways. The present work aimed to study a possible association of caffeine consumption with the cerebrospinal fluid (CSF) biomarkers, particularly Aβ. The study included 88 patients with AD or mild cognitive impairment. The consumption of caffeine and theobromine was evaluated using a validated food questionnaire. Quantification of caffeine and main active metabolites was performed with liquid chromatography coupled to tandem mass spectrometry. The levels of A(1-42), total tau, and phosphorylated tau in the CSF were determined using sandwich ELISA methods and other Aβ species, Aβ(X-38), Aβ(X-40), and Aβ(X-42), with the MSD Aβ Triplex assay. The concentration of caffeine was 0.79±1.15 μg/mL in the CSF and 1.20±1.88 μg/mL in the plasma. No correlation was found between caffeine consumption and Aβ42 in the CSF. However, a significant positive correlation was found between the concentrations of theobromine, both in the CSF and in the plasma, with Aβ42 in the CSF. Theobromine in the CSF was positively correlated with the levels of other xanthines in the CSF, but not in the plasma, suggesting that it may be formed by central metabolic pathways. In conclusion, caffeine consumption does not modify the levels of CSF biomarkers, and does not require to be controlled for when measuring CSF biomarkers in a clinical setting. Since theobromine is associated with a favorable Aβ profile in the CSF, the possibility that it might have a protective role in AD should be further investigated.

  5. Metaphor Comprehension in Alzheimer's Disease: Novelty Matters

    ERIC Educational Resources Information Center

    Amanzio, Martina; Geminiani, Giuliano; Leotta, Daniela; Cappa, Stefano

    2008-01-01

    The comprehension of non-literal language was investigated in 20 probable Alzheimer's disease (pAD) patients by comparing their performance to that of 20 matched control subjects. pAD patients were unimpaired in the comprehension of conventional metaphors and idioms. However, their performance was significantly lower in the case of…

  6. Diabetes and Alzheimer's disease crosstalk.

    PubMed

    Baglietto-Vargas, David; Shi, Jessica; Yaeger, Devin M; Ager, Rahasson; LaFerla, Frank M

    2016-05-01

    Despite intensive research efforts over the past few decades, the mechanisms underlying the etiology of sporadic Alzheimer's disease (AD) remain unknown. This fact is of major concern because the number of patients affected by this medical condition is increasing exponentially and the existing treatments are only palliative in nature and offer no disease modifying affects. Interestingly, recent epidemiological studies indicate that diabetes significantly increases the risk of developing AD, suggesting that diabetes may play a causative role in the development of AD pathogenesis. Therefore, elucidating the molecular interactions between diabetes and AD is of critical significance because it might offer a novel approach to identifying mechanisms that may modulate the onset and progression of sporadic AD cases. This review highlights the involvement of several novels pathological molecular mechanisms induced by diabetes that increase AD pathogenesis. Furthermore, we discuss novel findings in animal model and clinical studies involving the use of anti-diabetic compounds as promising therapeutics for AD.

  7. Effects of cognitive-communication stimulation for Alzheimer's disease patients treated with donepezil.

    PubMed

    Chapman, Sandra Bond; Weiner, Myron F; Rackley, Audette; Hynan, Linda S; Zientz, Jennifer

    2004-10-01

    This randomized study evaluated the combined effect of a cognitive-communication program plus an acetylcholinesterase inhibitor (donepezil; donepezil-plus-stimulation group; n = 26), as compared with donepezil alone (donepezil-only group; n = 28) in 54 patients with mild to moderate Alzheimer's disease (AD; Mini-Mental Status Examination score of 12- 28) ranging in age from 54 to 91 years. It was hypothesized that cognitive-communication stimulation in combination with donepezil would positively affect the following: (a) relevance of discourse, (b) performance of functional abilities, (c) emotional symptoms, (d) quality of life, and (e) overall global function, as measured by caregiver and participant report and standardized measures. Cognitive-communication, neuropsychiatric, functional performance, and quality of life evaluations were conducted at baseline and Month 4, the month after the 2-month active stimulation period. Follow-up evaluations were performed at Months 8 and 12. The stimulation program consisted of 12 hr of intervention over an 8-week period and involved participant-led discussions requiring homework, interactive sessions about AD, and discussions using salient life stories. Additive effects of active stimulation with donepezil were examined in 2 ways: (1) comparing mean group performance over time and (2) evaluating change scores from baseline. A Group x Time interaction was found for the donepezil-plus-stimulation group in the emotional symptoms of apathy and irritability as compared with the donepezil-only group. Evaluation of change scores from baseline to 12 months revealed a positive effect for the donepezil-plus-stimulation group on discourse and functional abilities with a trend on apathy, irritability, and patient-reported quality of life. In sum, the research revealed benefits to the donepezil-plus-stimulation group in the areas of discourse abilities, functional abilities, emotional symptoms, and overall global performance. This study

  8. Alpha1-chimaerin, a Rac1 GTPase-activating protein, is expressed at reduced mRNA levels in the brain of Alzheimer's disease patients

    PubMed Central

    Kato, Tomoko; Konishi, Yoshihiro; Shimohama, Shun; Beach, Thomas G.; Akatsu, Hiroyasu; Tooyama, Ikuo

    2015-01-01

    Alpha1-chimaerin is a GTPase-activating protein (GAP) for Rac1, a member of the Rho small GTPase family, whose action leads to the inactivation of Rac1. Rac1 activity is upregulated in Alzheimer's disease, but little is known about the role of α1-chimaerin. In this study, we investigated the expression and localization of α1-chimaerin mRNA in postmortem human brains from patients with Alzheimer's disease and control subjects. In situ hybridization studies demonstrated that α1-chimaerin was expressed by neurons in the neo-cortex of the temporal lobe and the hippocampus of both controls and Alzheimer's disease cases, with the signal intensity dramatically decreased in patients with Alzheimer's disease. Real-time PCR analysis confirmed a significant reduction of α1-chimaerin mRNA expression in the temporal cortex of Alzheimer's disease cases. In contrast, α2-chimaerin mRNA levels showed no significant difference between the groups. The present study showed reduced α1-chimaerin expression in the brain of Alzheimer's disease cases, suggesting a role in the upregulation of Rac1 activity during the disease process. PMID:25676811

  9. Predictors of Nursing Home Admission among Alzheimer's Disease Patients with Psychosis and/or Agitation

    PubMed Central

    Miller, Edward Alan; Schneider, Lon S.; Rosenheck, Robert A.

    2014-01-01

    Background The purpose of this study is to identify factors that predict nursing home placement among community-dwelling Alzheimer's Disease (AD) patients with psychosis or agitation in a randomized clinical trial. Methods 418 participants with AD enrolled in the CATIE-AD trial of anti-psychotic medications and having no evidence of nursing home use at baseline were followed 9 months post-random assignment using data provided by caregiver proxy. χ2 tests, t-tests and Cox proportional hazard modeling were used to examine the baseline correlates of nursing home use. Results Of outpatients with no prior nursing home use, 15.0% were placed in a nursing home in the 9 months following baseline, with the average time to placement being 122 days. Bivariate analyses indicate that those with prior outpatient mental health use at study entry were more likely to be admitted; so too were those with worse physical functioning—lower scores on the AD Cooperative Study Activities of Daily Living Scale (ADCS-ADL), lower utility scores on the Health Utility Index (HUI)-III, and worse cognition on the Mini-Mental State Examination. Controlling for other factors, non-Hispanic white race (hazard ratio [HR]=2.16) and prior mental health use (HR=1.87) increased the likelihood of admission. Those with higher ADCS-ADL scores were less likely to be placed (HR=0.97). Conclusion Factors leading to nursing home entry among psychotic/agitated AD patients are similar to the general population, though high incidence of nursing home entry highlights the importance of accounting for such utilization in health economic studies of AD outcomes. It also highlights the importance of using information on ADLs and other characteristics to develop profiles identifying those at greater or lesser risk of nursing home entry and, in so doing inform population planning associated with AD and identification of those patients and caregivers who might benefit most from interventions to prevent eventual placement

  10. The biological substrates of Alzheimer's disease

    SciTech Connect

    Scheibel, A.B.; Wechsler, A.F.; Brazier, M.A.B.

    1986-01-01

    This book contains 21 selections. Some of the titles are: Dementia of the Alzheimer Type: Genetic Aspects; Determination of Cerebral Metabolic Patterns in Dementia Using Positron Emission Tomography; Pathology of the Basal Forebrain in Alzheimer's Disease and Other Dementias; Characterization of Neurofibrillary Tangles with Monoclonal Antibodies Raised Against Alzheimer Neurofibrillary Tangles; and HLA Associations in Alzheimer's Disease.

  11. Raman spectroscopy of Alzheimer's diseased tissue

    NASA Astrophysics Data System (ADS)

    Sudworth, Caroline D.; Krasner, Neville

    2004-07-01

    Alzheimer's disease is one of the most common forms of dementia, and causes steady memory loss and mental regression. It is also accompanied by severe atrophy of the brain. However, the pathological biomarkers of the disease can only be confirmed and examined upon the death of the patient. A commercial (Renishaw PLC, UK) Raman system with an 830 nm NIR diode laser was used to analyse brain samples, which were flash frozen at post-mortem. Ethical approval was sought for these samples. The Alzheimer's diseased samples contained a number of biomarkers, including neuritic plaques and tangles. The Raman spectra were examined by order to differentiate between normal and Alzheimer's diseased brain tissues. Preliminary results indicate that Alzheimer's diseased tissues can be differentiated from control tissues using Raman spectroscopy. The Raman spectra differ in terms of peak intensity, and the presence of a stronger amide I band in the 1667 cm-1 region which occurs more prominently in the Alzheimer's diseased tissue. These preliminary results indicate that the beta-amyloid protein originating from neuritic plaques can be identified with Raman spectroscopy.

  12. Auditory spatial processing in Alzheimer's disease.

    PubMed

    Golden, Hannah L; Nicholas, Jennifer M; Yong, Keir X X; Downey, Laura E; Schott, Jonathan M; Mummery, Catherine J; Crutch, Sebastian J; Warren, Jason D

    2015-01-01

    The location and motion of sounds in space are important cues for encoding the auditory world. Spatial processing is a core component of auditory scene analysis, a cognitively demanding function that is vulnerable in Alzheimer's disease. Here we designed a novel neuropsychological battery based on a virtual space paradigm to assess auditory spatial processing in patient cohorts with clinically typical Alzheimer's disease (n = 20) and its major variant syndrome, posterior cortical atrophy (n = 12) in relation to healthy older controls (n = 26). We assessed three dimensions of auditory spatial function: externalized versus non-externalized sound discrimination, moving versus stationary sound discrimination and stationary auditory spatial position discrimination, together with non-spatial auditory and visual spatial control tasks. Neuroanatomical correlates of auditory spatial processing were assessed using voxel-based morphometry. Relative to healthy older controls, both patient groups exhibited impairments in detection of auditory motion, and stationary sound position discrimination. The posterior cortical atrophy group showed greater impairment for auditory motion processing and the processing of a non-spatial control complex auditory property (timbre) than the typical Alzheimer's disease group. Voxel-based morphometry in the patient cohort revealed grey matter correlates of auditory motion detection and spatial position discrimination in right inferior parietal cortex and precuneus, respectively. These findings delineate auditory spatial processing deficits in typical and posterior Alzheimer's disease phenotypes that are related to posterior cortical regions involved in both syndromic variants and modulated by the syndromic profile of brain degeneration. Auditory spatial deficits contribute to impaired spatial awareness in Alzheimer's disease and may constitute a novel perceptual model for probing brain network disintegration across the Alzheimer's disease

  13. Quantitative evaluation of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Duchesne, S.; Frisoni, G. B.

    2009-02-01

    We propose a single, quantitative metric called the disease evaluation factor (DEF) and assess its efficiency at estimating disease burden in normal, control subjects (CTRL) and probable Alzheimer's disease (AD) patients. The study group consisted in 75 patients with a diagnosis of probable AD and 75 age-matched normal CTRL without neurological or neuropsychological deficit. We calculated a reference eigenspace of MRI appearance from reference data, in which our CTRL and probable AD subjects were projected. We then calculated the multi-dimensional hyperplane separating the CTRL and probable AD groups. The DEF was estimated via a multidimensional weighted distance of eigencoordinates for a given subject and the CTRL group mean, along salient principal components forming the separating hyperplane. We used quantile plots, Kolmogorov-Smirnov and χ2 tests to compare the DEF values and test that their distribution was normal. We used a linear discriminant test to separate CTRL from probable AD based on the DEF factor, and reached an accuracy of 87%. A quantitative biomarker in AD would act as an important surrogate marker of disease status and progression.

  14. Biomarkers for Alzheimer's Disease Diagnosis.

    PubMed

    Mantzavinosa, Vasileios; Alexiou, Athanasios; Greig, Nigel H; Kamal, Mohammad A

    2017-02-03

    The dramatic increase in the population with dementia expected in the next decades is accompanied by the establishment of novel and innovated methods that will offer accurate and efficient detection of the disease in its early stages. While Alzheimer's disease is the most common cause of dementia, by the time is typically diagnosed substantial neuronal loss and neuropathological lesions can damaged many brain regions. The aim of this study is to investigate the main risk factors that affect and increase Alzheimer's disease progression over time even in cases with no significant memory impairment present. Several potential markers are discussed such as oxidative stress, metal ions, vascular disorders, protein dysfunctions and alterations in the mitochondrial populations. A multiparametric model of Alzheimer's biomarkers is presented according to the latest classification of the disease.

  15. Alzheimer's Disease | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Alzheimer's Disease Living with Alzheimer's Disease Past Issues / Winter 2015 Table of Contents ... delay or prevent the disease. Free Guide for Alzheimer's Caregivers Caring for a person with Alzheimer's disease ...

  16. Factors associated with psychotic symptoms in Alzheimer's disease

    PubMed Central

    Hirono, N.; Mori, E.; Yasuda, M.; Ikejiri, Y.; Imamura, T.; Shimomura, T.; Ikeda, M.; Hashimoto, M.; Yamashita, H.

    1998-01-01

    OBJECTIVES—Many clinical and biological factors have been reported to be associated with the presence of psychosis in patients with Alzheimer's disease, although the associations were variable. The aim of this study was to clarify factors associated with the presence of psychosis in patients with Alzheimer's disease.
METHODS—Psychiatric functioning was studied in 228 patients with Alzheimer's disease based on the results of the behavioural pathology in Alzheimer's disease rating scale or the neuropsychiatric inventory. The effects of sex, education level, age, duration of illness, cognitive function, and apolipoprotein E genotype were investigated for dichotomous psychotic status with a multiple logistic regression analysis.
RESULTS—Of the 228 patients with Alzheimer's disease, 118 (51.8%) showed evidence of delusions or hallucinations. Of these, 94 had delusions only, three had hallucinations only, and 21 had both. Older age, female sex, longer duration of illness, and more severe cognitive impairment were the factors independently associated with the presence of psychosis. The presence of psychosis was not significantly related to either educational level or apolipoprotein E genotype.
CONCLUSIONS—Age, sex, and severity of illness were independent factors associated with the presence of psychosis in patients with Alzheimer's disease. The reason why some patients with Alzheimer's disease develop psychosis remains unclear. There may be distinctive subtypes of Alzheimer's disease or the presence of individual factors which affect the development of psychosis.

 PMID:9598682

  17. Inductive reasoning in Alzheimer's disease.

    PubMed

    Smith, E E; Rhee, J; Dennis, K; Grossman, M

    2001-12-01

    We evaluated knowledge of basic level and superordinate semantic relations and the role of cognitive resources during inductive reasoning in probable Alzheimer's disease (AD). Nineteen mildly demented AD patients and 17 healthy control subjects judged the truthfulness of arguments with a premise and a conclusion that contain familiar concepts coupled with "blank" predicates, such as "Spiders contain phosphatidylcholine; therefore all insects contain phosphatidylcholine." Like healthy control subjects, AD patients were relatively insensitive to the typicality of the premise category when judging the strength of arguments with a conclusion containing a basic-level concept, but were relatively sensitive to typicality during judgments of arguments containing a superordinate in the conclusion. Moreover, AD patients resembled control subjects in judging arguments with an immediate superordinate in the conclusion compared to arguments with a distant superordinate. AD patients differed from control subjects because they could not take advantage of two premises in an argument containing basic-level concepts. We conclude that semantic knowledge is sufficiently preserved in AD to support inductive reasoning, but that limited cognitive resources may interfere with AD patients' ability to consider the entire spectrum of information available during semantic challenges.

  18. Adaptive walking in Alzheimer's disease.

    PubMed

    Orcioli-Silva, Diego; Simieli, Lucas; Barbieri, Fabio Augusto; Stella, Florindo; Gobbi, Lilian Teresa Bucken

    2012-01-01

    The aim of this study is to analyze dual-task effects on free and adaptive gait in Alzheimer's disease (AD) patients. Nineteen elders with AD participated in the study. A veteran neuropsychiatrist established the degree of AD in the sample. To determine dual-task effects on free and adaptive gait, patients performed five trials for each experimental condition: free and adaptive gait with and without a dual-task (regressive countdown). Spatial and temporal parameters were collected through an optoelectronic tridimensional system. The central stride was analyzed in free gait, and the steps immediately before (approaching phase) and during the obstacle crossing were analyzed in adaptive gait. Results indicated that AD patients walked more slowly during adaptive gait and free gait, using conservative strategies when confronted either with an obstacle or a secondary task. Furthermore, patients sought for stability to perform the tasks, particularly for adaptive gait with dual task, who used anticipatory and online adjustments to perform the task. Therefore, the increase of task complexity enhances cognitive load and risk of falls for AD patients.

  19. Adaptive Walking in Alzheimer's Disease

    PubMed Central

    Orcioli-Silva, Diego; Simieli, Lucas; Barbieri, Fabio Augusto; Stella, Florindo; Gobbi, Lilian Teresa Bucken

    2012-01-01

    The aim of this study is to analyze dual-task effects on free and adaptive gait in Alzheimer's disease (AD) patients. Nineteen elders with AD participated in the study. A veteran neuropsychiatrist established the degree of AD in the sample. To determine dual-task effects on free and adaptive gait, patients performed five trials for each experimental condition: free and adaptive gait with and without a dual-task (regressive countdown). Spatial and temporal parameters were collected through an optoelectronic tridimensional system. The central stride was analyzed in free gait, and the steps immediately before (approaching phase) and during the obstacle crossing were analyzed in adaptive gait. Results indicated that AD patients walked more slowly during adaptive gait and free gait, using conservative strategies when confronted either with an obstacle or a secondary task. Furthermore, patients sought for stability to perform the tasks, particularly for adaptive gait with dual task, who used anticipatory and online adjustments to perform the task. Therefore, the increase of task complexity enhances cognitive load and risk of falls for AD patients. PMID:22991684

  20. The factor structure of the Cornell Scale for Depression in Dementia among probable Alzheimer's disease patients.

    PubMed

    Harwood, D G; Ownby, R L; Barker, W W; Duara, R

    1998-01-01

    The authors rated 137 outpatients with probable Alzheimer's disease (AD) on the Cornell Scale for Depression in Dementia (CSDD) as part of routine evaluation. Principal-factors analysis with varimax rotation resulted in a four-factor solution that accounted for 43.1% of the common variance. The four factors included general depression (lack of reactivity to pleasant events, poor self-esteem, pessimism, loss of interest, physical complaints, psychomotor retardation, sadness); rhythm disturbances (difficulty falling asleep, multiple night awakenings, early morning awakenings, weight loss, diurnal variation of mood); agitation/psychosis (agitation, mood-congruent delusions, suicide); and negative symptoms (appetite loss, weight loss, lack of energy, loss of interest, lack of reactivity to pleasant events). The observed factor structure showed moderate concordance with the five symptom clusters proposed in the original presentation of the CSDD.

  1. Exercising restraint: clinical, legal and ethical considerations for the patient with Alzheimer's disease.

    PubMed

    McBrien, Barry

    2007-04-01

    The number of older people using emergency care is increasing steadily and older people account for over half of all emergency admissions. In the emergency setting, nurses caring for older people with Alzheimer's disease can be faced with many complex ethical and legal challenges. Moreover, challenges such as the use of physical restraint can precipitate conflict when the nurse is placed in the precarious position of doing good, respecting autonomy and avoiding paternalism. Although, there is no complete set of "rules" that can provide nurses with an answer to each dilemma, it is of significant value for nurses to have sound knowledge of ethical and legal positions in order to analyse the many complex situations that they may encounter.

  2. [Predementia Alzheimer's disease. Benefits of early diagnosis].

    PubMed

    Viloria, Aurora

    2011-10-01

    Given population aging and the rise in the number of persons with Alzheimer's disease, measures that aim not only to delay but also to prevent the development of this disease are increasingly required. Advances in the diagnosis of Alzheimer's disease support the need for a review of current clinical standards for mild cognitive impairment and provide new goals in the early treatment of this disease. The current diagnostic process should be refocussed toward the pathological substrate of this disease rather than symptoms in order to initiate therapeutic measures as soon as possible without waiting for clinical manifestations to appear. Such an approach is essential in patients with greater cognitive reserve, in whom the lesions are usually more severe at diagnosis and treatment is less effective. To identify disease-modifying therapies to delay the onset of the clinical symptoms of Alzheimer's disease in cognitively intact persons at high risk, biomarkers for this disease must be validated. A single biomarker is unlikely to provide the required diagnostic accuracy and therefore a multimodal approach, incorporating biochemical, neuropathological and anatomical and metabolic neuroimaging methods, should be employed. To optimize the results of drugs under investigation, a combination of biomarkers should be used to select appropriate participants in the earliest phases of the disease, and disease progression should be followed-up. Early diagnosis might clarify essential questions in the care of patients with Alzheimer's disease, such as the possibility of distinguishing among various subtypes, thus encouraging the development of optimal treatments for each. The ultimate goal is to develop disease-modifying treatments that could be initiated early, while patients are asymptomatic or only minimally symptomatic, to maintain their quality of life.

  3. Three-dimensional quantitative imaging of telomeres in buccal cells identifies mild, moderate, and severe Alzheimer's disease patients.

    PubMed

    Mathur, Shubha; Glogowska, Aleksandra; McAvoy, Elizabeth; Righolt, Christiaan; Rutherford, Jaclyn; Willing, Cornelia; Banik, Upama; Ruthirakuhan, Myuri; Mai, Sabine; Garcia, Angeles

    2014-01-01

    Using three-dimensional (3D) telomeric analysis of buccal cells of 82 Alzheimer's disease (AD) patients and cognitively normal age and gender-matched controls, we have for the first time examined changes in the 3D nuclear telomeric architecture of buccal cells among levels of AD severity based on five 3D parameters: i) telomere length, ii) telomere number, iii) telomere aggregation, iv) nuclear volume, and v) a/c ratio, a measure of spatial telomere distribution. Our data indicate that matched controls have significantly different 3D telomere profiles compared to mild, moderate, and severe AD patients (p < 0.0001). Distinct profiles were also evident for each AD severity group. An increase in telomere number and aggregation concomitant with a decrease in telomere length from normal to severe AD defines the individual stages of the disease (p < 0.0001).

  4. β-methylamino-L-alanine (BMAA) is not found in the brains of patients with confirmed Alzheimer's disease.

    PubMed

    Meneely, Julie P; Chevallier, Olivier P; Graham, Stewart; Greer, Brett; Green, Brian D; Elliott, Christopher T

    2016-11-08

    Controversy surrounds the proposed hypothesis that exposure to β-methylamino-L-alanine (BMAA) could play a role in various neurodegenerative conditions including Alzheimer's disease (AD). Here we present the results of the most comprehensive scientific study on BMAA detection ever undertaken on brain samples from patients pathologically confirmed to have suffered from AD, and those from healthy volunteers. Following the full validation of a highly accurate and sensitive mass spectrometric method, no trace of BMAA was detected in the diseased brain or in the control specimens. This contradicts the findings of other reports and calls into question the significance of this compound in neurodegenerative disease. We have attempted to explain the potential causes of misidentification of BMAA in these studies.

  5. Hemodynamic aspects of Alzheimer's disease.

    PubMed

    Nagata, Ken; Sato, Mika; Satoh, Yuichi; Watahiki, Yasuhito; Kondoh, Yasushi; Sugawara, Maki; Box, Georgia; Wright, David; Leung, Sumie; Yuya, Hiromichi; Shimosegawa, Eku

    2002-11-01

    Neuroradiological functional imaging techniques demonstrate the patterns of hypoperfusion and hypometabolism that are thought to be useful in the differential diagnosis of Alzheimer's disease (AD) from other dementing disorders. Besides the distribution patterns of perfusion or energy metabolism, vascular transit time (VTT), vascular reactivity (VR), and oxygen extraction fraction (OEF), which can be measured with positron emission tomography (PET), provide hemodynamic aspects of brain pathophysiology. In order to evaluate the hemodynamic features of AD, PET studies were carried out in 20 patients with probable AD and 20 patients with vascular dementia (VaD). The PET findings were not included in their diagnostic process of AD. Using oxygen-15-labeled compounds, cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO(2)), OEF, cerebral blood volume, and VTT were measured quantitatively during resting state. To evaluate VR, CBF was also measured during CO(2) inhalation. There was a significant increase in OEF in and around the parietotemporal cortices, but both VTT and VR were well preserved in patients with AD. By contrast, VR was markedly depressed and VTT was mildly prolonged in patients with VaD. Thus, from the hemodynamic point of view, the preservation of vascular reserve may be a distinct difference between AD and VaD. Furthermore, this indicates a hemodynamic integrity of the vasculature in the level of arterioles in AD.

  6. Magnetic Analysis of Post-mortem Hippocampal Tissue from Alzheimer's Patients: Changes with Progression of the Disease.

    NASA Astrophysics Data System (ADS)

    Fuller, M.; Zinin, P.; Favia, J.; Tatsumi, L.; Kletetschka, G.; Adachi, T.

    2007-12-01

    Increases of iron in the human brain with age have been observed and may be accompanied by the development of neurodegenerative diseases, such as Alzheimer's. We have measured the magnetic characteristics of several sets of slides of hippocampal tissue from deceased Alzheimer patients. The slides were made available by the Harvard Brain Bank. The pathology of the tissue was classified in the Braak stages I to VI used to describe the progression of the disease. In general, the slides from patients with higher Braak stages and development of fibrillary tangles and plaques had greater magnetic moments than did those with Braak stage II. However, the peak values were at stage IV and V. To mitigate errors due to the inevitable differences in masses of the tissue on individual slides and their precise location in the hippocampus, ratios of magnetic properties were also observed. Ratios of Anhysteretic Remanent Magnetizaton (ARM) to Isothermal Remanent Magnetization (IRM) were obtained and showed a decrease from Stage II to the more advanced stages, with the minimum values at stages IV and V. The acquisition and demagnetization of IRM are consistent with the presence of magnetite, but also indicate a magnetically harder phase.

  7. Effects of change in FreeSurfer version on classification accuracy of patients with Alzheimer's disease and mild cognitive impairment.

    PubMed

    Chepkoech, Joy-Loi; Walhovd, Kristine B; Grydeland, Håkon; Fjell, Anders M

    2016-05-01

    Studies have found non-negligible differences in cortical thickness estimates across versions of software that are used for processing and quantifying MRI-based cortical measurements, and issues have arisen regarding these differences, as obtained estimates could potentially affect the validity of the results. However, more critical for diagnostic classification than absolute thickness estimates across versions is the inter-subject stability. We aimed to investigate the effect of change in software version on classification of older persons in groups of healthy, mild cognitive impairment and Alzheimer's Disease. Using MRI samples of 100 older normal controls, 100 with mild cognitive impairment and 100 Alzheimer's Disease patients obtained from the Alzheimer's Disease Neuroimaging Initiative database, we performed a standard reconstruction processing using the FreeSurfer image analysis suite versions 4.1.0, 4.5.0 and 5.1.0. Pair-wise comparisons of cortical thickness between FreeSurfer versions revealed significant differences, ranging from 1.6% (4.1.0 vs. 4.5.0) to 5.8% (4.1.0 vs. 5.1.0) across the cortical mantle. However, change of version had very little effect on detectable differences in cortical thickness between diagnostic groups, and there were little differences in accuracy between versions when using entorhinal thickness for diagnostic classification. This lead us to conclude that differences in absolute thickness estimates across software versions in this case did not imply lacking validity, that classification results appeared reliable across software versions, and that classification results obtained in studies using different FreeSurfer versions can be reliably compared. Hum Brain Mapp 37:1831-1841, 2016. © 2016 Wiley Periodicals, Inc.

  8. Energy expenditure, energy intake, and weight loss in Alzheimer disease.

    PubMed

    Poehlman, E T; Dvorak, R V

    2000-02-01

    Alzheimer disease is one of the leading causes of death among older individuals. Unexplained weight loss and cachexia are frequent clinical findings in patients with Alzheimer disease. Thus, it has been postulated that Alzheimer disease may be associated with dysfunction in body weight regulation. This brief review examines the interrelations among energy intake, energy expenditure, and body composition in Alzheimer disease. We explored whether abnormally high daily energy expenditures, low energy intakes, or both contribute to unexplained weight loss and a decline in nutritional status. Specifically, we considered studies that examined energy intake, body composition, and daily energy expenditure and its components. The application of doubly labeled water and indirect calorimetry to understand the etiology of wasting has increased our knowledge regarding the relation among energy expenditure, physical activity levels, and body composition in Alzheimer disease patients. Although the number of studies are limited, results do not support the notion that a hypermetabolic state contributes to unexplained weight loss in Alzheimer disease, even in cachectic patients. Recent findings are presented suggesting an association between abnormally elevated levels of physical activity energy expenditure and elevated appendicular skeletal muscle mass and energy intake in Alzheimer disease patients. Clinical strategies aimed at developing lifestyle and dietary interventions to maintain adequate energy intake, restore energy balance, and maintain skeletal muscle mass should be a future area of investigation in Alzheimer disease research.

  9. Are Judgments of Semantic Relatedness Systematically Impaired in Alzheimer's Disease?

    ERIC Educational Resources Information Center

    Hornberger, M.; Bell, B.; Graham, K. S.; Rogers, T. T.

    2009-01-01

    We employed a triadic comparison task in patients with Alzheimer's disease (AD) and healthy controls to contrast (a) multidimensional scaling (MDS) and accuracy-based assessments of semantic memory, and (b) degraded-store versus degraded-access accounts of semantic impairment in Alzheimer's disease (AD). Similar to other studies using triadic…

  10. Development and Implementation of Nonpharmacologic Protocols for the Management of Patients with Alzheimer's Disease and Their Families in a Multiracial Primary Care Setting

    ERIC Educational Resources Information Center

    Austrom, Mary Guerriero; Damush, Teresa M.; Hartwell, Cora West; Perkins, Tony; Unverzagt, Frederick; Boustani, Malaz; Hendrie, Hugh C.; Callahan, Christopher M.

    2004-01-01

    Purpose. Most patients and families with dementia are cared for in primary care clinics. These clinics are seldom designed to provide the necessary comprehensive care. The purpose of this article is to describe nonpharmacologic protocols for the management of patients with Alzheimer's disease and their families that are administered as part of a…

  11. Cerebrolysin improves symptoms and delays progression in patients with Alzheimer's disease and vascular dementia.

    PubMed

    Allegri, R F; Guekht, A

    2012-04-01

    Dementia is the result of various cerebral disorders, leading to an acquired loss of memory and impaired cognitive ability. The most common forms are Alzheimer's disease (AD) and vascular dementia (VaD). Neurotrophic factors are essential for the survival and differentiation of developing neurons and protecting them against damage under pathologic conditions. Cerebrolysin is a peptide preparation that mimics the pleiotropic effects of neurotrophic factors. Several clinical trials investigating the therapeutic efficacy of Cerebrolysin in AD and VaD have confirmed the proof of concept. The results of these trials have shown statistically significant and clinically relevant treatment effects of Cerebrolysin on cognitive, global and functional domains in mild to moderately severe stages of dementia. Doses of 10 and 30 mL were the most effective, but higher doses of up to 60 mL turned out to be most effective in improving neuropsychiatric symptoms, which become relevant at later stages of the disease. Combining treatment with cholinesterase inhibitors and Cerebrolysin indicated long-term synergistic treatment effects in mild to moderate AD. The efficacy of Cerebrolysin persisted for up to several months after treatment suggesting Cerebrolysin has not merely symptomatic benefits, but a disease-delaying potential. This paper reviews the clinical efficacy of Cerebrolysin in the treatment of dementia. Data were obtained from international, multicenter, randomized clinical trials performed in compliance with Good Clinical Practice and the principles of the Declaration of Helsinki (1964) and subsequent revisions.

  12. Caring for Alzheimer's Patients. Supplement to Caregivers' Practical Help to Assist Those Who Care for Patients with Dementia Related Diseases = El Cuidado de los Pacientes de Alzheimer. Suplemento de Ayuda Practica para las Personas Encargadas para Ayudar a los que Cuidan a Pacientes que Sufren de Enfermedades Relacionadas con la Demencia.

    ERIC Educational Resources Information Center

    New York State Office for the Aging, Albany.

    This manual is intended for caregivers of homebound patients with Alzheimer's disease and others who are mentally impaired. It deals with the nature of Alzheimer's, the decline in a patient's abilities, information about available services, and legal and financial issues. The manual provides guidance and suggestions to lessen the daily stress…

  13. Epileptic activity in Alzheimer's disease: causes and clinical relevance.

    PubMed

    Vossel, Keith A; Tartaglia, Maria C; Nygaard, Haakon B; Zeman, Adam Z; Miller, Bruce L

    2017-04-01

    Epileptic activity is frequently associated with Alzheimer's disease; this association has therapeutic implications, because epileptic activity can occur at early disease stages and might contribute to pathogenesis. In clinical practice, seizures in patients with Alzheimer's disease can easily go unrecognised because they usually present as non-motor seizures, and can overlap with other symptoms of the disease. In patients with Alzheimer's disease, seizures can hasten cognitive decline, highlighting the clinical relevance of early recognition and treatment. Some evidence indicates that subclinical epileptiform activity in patients with Alzheimer's disease, detected by extended neurophysiological monitoring, can also lead to accelerated cognitive decline. Treatment of clinical seizures in patients with Alzheimer's disease with select antiepileptic drugs (AEDs), in low doses, is usually well tolerated and efficacious. Moreover, studies in mouse models of Alzheimer's disease suggest that certain classes of AEDs that reduce network hyperexcitability have disease-modifying properties. These AEDs target mechanisms of epileptogenesis involving amyloid β and tau. Clinical trials targeting network hyperexcitability in patients with Alzheimer's disease will identify whether AEDs or related strategies could improve their cognitive symptoms or slow decline.

  14. Posture Recognition in Alzheimer's Disease

    ERIC Educational Resources Information Center

    Mozaz, Maria; Garaigordobil, Maite; Rothi, Leslie J. Gonzalez; Anderson, Jeffrey; Crucian, Gregory P.; Heilman, Kenneth M.

    2006-01-01

    Background: Apraxia is neurologically induced deficit in the ability perform purposeful skilled movements. One of the most common forms is ideomotor apraxia (IMA) where spatial and temporal production errors are most prevalent. IMA can be associated Alzheimer's disease (AD), even early in its course, but is often not identified possibly because…

  15. Genetic heterogeneity and Alzheimer`s disease

    SciTech Connect

    Schellenberg, G.D.; Wijsman, E.M.; Bird, T.D.

    1994-09-01

    In some early-onset Alzheimer`s disease (AD) families, inheritance is autosomal dominant. (Early-onset AD is arbitarily defined as onset at {le} 60 years.) Two loci have been identified which are causative for early-onset familial AD (FAD). One is the amyloid precursor protein gene in which specific mutation have been identified. The second is a locus at 14q24.3 (AD3) which has been localized by linkage analysis; the gene and specific mutations have not been identified. Linkage studies place this locus between D14S61 and D14S63. These 2 loci, however, do not account for all early-onset FAD. The Volga German (VG) kindreds are descendants of families which emigrated from Germany to the Volga river region of Russia and subsequently to the US; AD in these families is hypothesized to be the result of a common genetic founder. The average age-at-onset in these families is 57 years. Linkage analysis for this group has been negative for the APP gene and for chromosome 14 markers. Thus, there is at least 1 other early-onset FAD locus. Recently, the {epsilon}4 allele of apolipoprotein E (ApoE) was identified as a risk-factor for late-onset AD. In a series of 53 late-onset kindreds, a strong genetic association was observed between the ApoE {epsilon}4 allele and AD. However, when linkage analysis was performed using a highly polymorphic locus at the ApoCII gene, which is within 30 kb of ApoE, significant evidence for co-segregation was not observed. This and other data suggests that while ApoE is an age-at-onset modifying locus, another gene(s), located elsewhere, contribute(s) to late-onset AD. Thus, there is probably at least 1 other late-onset locus. Once the VG locus is identified, it will be possible to determine whether an allelic variant of this locus is responsible for late-onset FAD.

  16. Alzheimer's disease and euthanasia.

    PubMed

    Alvargonzález, David

    2012-12-01

    Employing the tenets of philosophical materialism, this paper discusses the ethical debate surrounding assisted suicide for persons suffering end-stage Alzheimer's. It first presents a classification of the dissociative situations between "human individual" and "human person". It then moves on to discuss challenges to diagnosed persons and their caregivers in relation to the cardinal virtues of Spinozistic ethics--strength of character (fortitudo), firmness (animositas) and generosity (generositas). Finally, a number of ideas attached to the debate--"right of choice", "death with dignity", "quality of life" and "compassion in dying"--are discussed in order to clarify their foundations.

  17. Apolipoprotein E alleles in Alzheimer`s and Parkinson`s patients

    SciTech Connect

    Poduslo, S.E.; Schwankhaus, J.D.

    1994-09-01

    A number of investigators have found an association between the apolipoprotein E4 allele and Alzheimer`s disease. The E4 allele appears at a higher frequency in late onset familial Alzheimer`s patients. In our studies we obtained blood samples from early and late onset familial and sporadic Alzheimer`s patients and spouses, as well as from Parkinson`s patients. The patients were diagnosed as probable Alzheimer`s patients after a neurological examination, extensive blood work, and a CAT scan. The diagnosis was made according to the NINCDS-ADRDA criteria. The apolipoprotein E4 polymorphism was detected after PCR amplification of genomic DNA, restriction enzyme digestion with Hhal, and polyacrylamide gel electrophoresis. Ethidium bromide-stained bands at 91 bp were designated as allele 3, at 83 bp as allele 2, and at 72 bp as allele 4. Of the 84 probable Alzheimer`s patients (all of whom were Caucasian), 47 were heterozygous and 13 were homozygous for the E4 allele. There were 26 early onset patients; 13 were heterozygous and 7 homozygous for the E4 allele. The frequencies for the E4 allele for late onset familial patients was 0.45 and for sporadic patients was 0.37. We analyzed 77 spouses with an average age of 71.9 {plus_minus} 7.4 years as controls, and 15 were heterozygous for the E4 allele for an E4 frequency of 0.097. Of the 53 Parkinson`s patients, 11 had the E4 allele for a frequency of 0.113. Thus our findings support the association of the ApoE4 allele with Alzheimer`s disease.

  18. A comparison of emotional decoding abilities in patients with amnestic mild cognitive impairment, very mild and mild Alzheimer's disease.

    PubMed

    Klimkowicz-Mrowiec, Aleksandra; Krzywoszanski, Lukasz; Spisak, Karolina; Donohue, Bryan E; Szczudlik, Andrzej; Slowik, Agnieszka

    2014-02-01

    Deficits in emotional decoding abilities were described in patients with Alzheimer's dementia and amnestic type of mild cognitive impairment (a-MCI). However the pattern of decline and its dependency on the type of emotional stimuli has not been investigated so far. In our study, 5 sets of cartoon-like drawings portraying various human emotions of increasing complexity were presented to patients with very mild and mild Alzheimer's dementia, a-MCI and control subjects. Patients with Alzheimer's dementia, a-MCI and control subjects decoded emotions with similar accuracy. The pattern of decoding abilities was similar in Alzheimer's dementia, a-MCI patients and healthy control subjects. Decoding abilities depended on a manner the emotional stimuli were presented.

  19. The influence of phospho-τ on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease.

    PubMed

    Merino-Serrais, Paula; Benavides-Piccione, Ruth; Blazquez-Llorca, Lidia; Kastanauskaite, Asta; Rábano, Alberto; Avila, Jesús; DeFelipe, Javier

    2013-06-01

    The dendritic spines on pyramidal cells represent the main postsynaptic elements of cortical excitatory synapses and they are fundamental structures in memory, learning and cognition. In the present study, we used intracellular injections of Lucifer yellow in fixed tissue to analyse over 19 500 dendritic spines that were completely reconstructed in three dimensions along the length of the basal dendrites of pyramidal neurons in the parahippocampal cortex and CA1 of patients with Alzheimer's disease. Following intracellular injection, sections were immunostained for anti-Lucifer yellow and with tau monoclonal antibodies AT8 and PHF-1, which recognize tau phosphorylated at Ser202/Thr205 and at Ser396/404, respectively. We observed that the diffuse accumulation of phospho-tau in a putative pre-tangle state did not induce changes in the dendrites of pyramidal neurons, whereas the presence of tau aggregates forming intraneuronal neurofibrillary tangles was associated with progressive alteration of dendritic spines (loss of dendritic spines and changes in their morphology) and dendrite atrophy, depending on the degree of tangle development. Thus, the presence of phospho-tau in neurons does not necessarily mean that they suffer severe and irreversible effects as thought previously but rather, the characteristic cognitive impairment in Alzheimer's disease is likely to depend on the relative number of neurons that have well developed tangles.

  20. Immunotherapeutic Approaches to Alzheimer's Disease

    NASA Astrophysics Data System (ADS)

    Monsonego, Alon; Weiner, Howard L.

    2003-10-01

    Although neurodegenerative diseases such as Alzheimer's disease are not classically considered mediated by inflammation or the immune system, in some instances the immune system may play an important role in the degenerative process. Furthermore, it has become clear that the immune system itself may have beneficial effects in nervous system diseases considered neurodegenerative. Immunotherapeutic approaches designed to induce a humoral immune response have recently been developed for the treatment of Alzheimer's disease. These studies have led to human trials that resulted in both beneficial and adverse effects. In animal models, it has also been shown that immunotherapy designed to induce a cellular immune response may be of benefit in central nervous system injury, although T cells may have either a beneficial or detrimental effect depending on the type of T cell response induced. These areas provide a new avenue for exploring immune system-based therapy of neurodegenerative diseases and will be discussed here with a primary focus on Alzheimer's disease. We will also discuss how these approaches affect microglia activation, which plays a key role in therapy of such diseases.

  1. Animal models of Alzheimer disease.

    PubMed

    LaFerla, Frank M; Green, Kim N

    2012-11-01

    Significant insights into the function of genes associated with Alzheimer disease and related dementias have occurred through studying genetically modified animals. Although none of the existing models fully reproduces the complete spectrum of this insidious human disease, critical aspects of Alzheimer pathology and disease processes can be experimentally recapitulated. Genetically modified animal models have helped advance our understanding of the underlying mechanisms of disease and have proven to be invaluable in the preclinical evaluation of potential therapeutic interventions. Continuing refinement and evolution to yield the next generation of animal models will facilitate successes in producing greater translational concordance between preclinical studies and human clinical trials and eventually lead to the introduction of novel therapies into clinical practice.

  2. The economics of Alzheimer disease.

    PubMed

    Leung, G M; Yeung, R Y T; Chi, I; Chu, L W

    2003-01-01

    Economic assessments of health and healthcare have become an integral part of policy decisions in the last decade. Increasingly, this trend is extending to medical decision-making in day-to-day patient-provider interactions. Alzheimer disease (AD) offers a potent example of the clinical and economic issues at stake with its diagnostic techniques, pharmacotherapies, and public health and policy implications. This review introduces basic economic concepts in examining the impact of AD and related care. It presents a summary of the latest economics research on cost estimates of AD and on economic evaluations of diagnostic and management interventions in terms of cost-of-illness and cost-effectiveness studies respectively. Empirical and conceptual issues about the interpretation of costs and the uses of evaluative methods are also discussed. We found that the economic costs attributable to AD care is highly variable mostly due to non-standardised methodologies and geographical variations in care patterns. There is, however, little doubt that the impact is substantial and is expected to worsen with the demographic, epidemiologic, technologic and economic transitions worldwide. There are comparatively fewer studies on the cost-effectiveness of interventions in AD. Most of the published work revolves around pharmacotherapeutics while relatively little has been done on diagnostics, patient care programmes and programmes for caregivers. We conclude that there are significant opportunities to strengthen research on standardised cost-of-illness analyses and new cost-effectiveness studies on a broader range of AD interventions.

  3. Medical foods for Alzheimer's disease.

    PubMed

    Shah, Raj C

    2011-06-01

    Alzheimer's disease (AD) is a neurodegenerative condition associated with cognitive loss, behavioural changes, functional ability decline and caregiver burden. Given the worldwide public health impact of AD, novel interventions to reduce suffering experienced by AD patients need to be developed. Foods may offer a mechanism for intervention complementary to drugs, devices, biologicals and vaccines. Apart from foods with health claims (including dietary supplements), medical foods are also being explored as an intervention option. The purpose of this article is to describe how medical foods may complement other interventions for AD patients by: (i) defining what a medical food is; (ii) discussing whether AD is a condition amenable to medical food intervention; (iii) reviewing current clinical trial data on medical foods used in participants with AD; and (iv) highlighting steps needed to establish a more comprehensive framework for developing medical foods for AD. While medical foods may be defined differently in other countries, the US Orphan Drug Act of 1998 defined a medical food as a food formulated for enteral intake, taken under physician supervision, and intended to meet the distinctive nutritional requirements identified for a disease or condition. For AD to be amenable to medical food intervention, it must: (i) result in limited or impaired capacity to ingest, digest, absorb or metabolize ordinary foodstuff or certain nutrients; or (ii) have unique, medically determined nutrient requirements; and (iii) require dietary management that cannot be achieved by modification of the normal diet alone. While these criteria are most likely met in advanced AD, identifying unique nutritional requirements in early AD that cannot be met by normal diet modification requires a better understanding of AD pathophysiology. A PubMed search using the terms 'medical food' and 'Alzheimer', limited to clinical trials published in English with human participants with AD aged >65

  4. The behavioural/dysexecutive variant of Alzheimer's disease: clinical, neuroimaging and pathological features.

    PubMed

    Ossenkoppele, Rik; Pijnenburg, Yolande A L; Perry, David C; Cohn-Sheehy, Brendan I; Scheltens, Nienke M E; Vogel, Jacob W; Kramer, Joel H; van der Vlies, Annelies E; La Joie, Renaud; Rosen, Howard J; van der Flier, Wiesje M; Grinberg, Lea T; Rozemuller, Annemieke J; Huang, Eric J; van Berckel, Bart N M; Miller, Bruce L; Barkhof, Frederik; Jagust, William J; Scheltens, Philip; Seeley, William W; Rabinovici, Gil D

    2015-09-01

    A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer's disease pathology. The description of this rare Alzheimer's disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer's disease with a behavioural-predominant presentation (behavioural Alzheimer's disease) and a neuropathological diagnosis of high-likelihood Alzheimer's disease (n = 17) and/or biomarker evidence of Alzheimer's disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer's disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer's disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer's disease: 53%; dysexecutive Alzheimer's disease: 83%) than behavioural (behavioural Alzheimer's disease: 25%; dysexecutive Alzheimer's disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer's disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer's disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer's disease and 40% of those with the dysexecutive syndrome carried at least one APOE ε4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer's disease (typical Alzheimer's disease, n = 58), autopsy-confirmed/Alzheimer's disease biomarker-negative behavioural variant frontotemporal dementia (n = 59

  5. The importance of parkinsonian signs for gait and balance in patients with Alzheimer's disease of mild degree.

    PubMed

    Tangen, Gro Gujord; Bergland, Astrid; Engedal, Knut; Mengshoel, Anne Marit

    2017-01-01

    Parkinsonian signs are common in patients with Alzheimer's disease (AD) of mild degree and predict functional decline, but their relationship with gait speed and balance is unclear. The aims of this study were to describe characteristics of patients with parkinsonian signs among 98 patients with AD of mild degree (with no comorbid Parkinson's disease), and to examine associations between parkinsonian signs with gait speed and balance. A cross sectional study at a memory clinic was conducted. Presence of each parkinsonian sign (bradykinesia, rigidity and tremor) was derived from the UPDRS, regular gait speed was recorded over 10m and balance were assessed using the Mini-Balance Evaluation Systems Test (Mini-BESTest). Bradykinesia was present in 30.6% of the sample, rigidity in 13.3% and tremor only in one patient. Patients with bradykinesia were older, had worse cognitive impairment and worse gait and balance performance than those without bradykinesia. More men than women had rigidity. Bradykinesia was significantly associated with mini-BESTest after adjusting for demographic factors (p<0.001, explaining 13.3% of the variance), but was not significantly associated with gait speed. Rigidity was not associated with either gait speed or balance. We conclude that assessment of bradykinesia should be included in examination of balance control in patients with AD of mild degree.

  6. Cerebrovascular disease in ageing and Alzheimer's disease.

    PubMed

    Love, Seth; Miners, J Scott

    2016-05-01

    Cerebrovascular disease (CVD) and Alzheimer's disease (AD) have more in common than their association with ageing. They share risk factors and overlap neuropathologically. Most patients with AD have Aβ amyloid angiopathy and degenerative changes affecting capillaries, and many have ischaemic parenchymal abnormalities. Structural vascular disease contributes to the ischaemic abnormalities in some patients with AD. However, the stereotyped progression of hypoperfusion in this disease, affecting first the precuneus and cingulate gyrus, then the frontal and temporal cortex and lastly the occipital cortex, suggests that other factors are more important, particularly in early disease. Whilst demand for oxygen and glucose falls in late disease, functional MRI, near infrared spectroscopy to measure the saturation of haemoglobin by oxygen, and biochemical analysis of myelin proteins with differential susceptibility to reduced oxygenation have all shown that the reduction in blood flow in AD is primarily a problem of inadequate blood supply, not reduced metabolic demand. Increasing evidence points to non-structural vascular dysfunction rather than structural abnormalities of vessel walls as the main cause of cerebral hypoperfusion in AD. Several mediators are probably responsible. One that is emerging as a major contributor is the vasoconstrictor endothelin-1 (EDN1). Whilst there is clearly an additive component to the clinical and pathological effects of hypoperfusion and AD, experimental and clinical observations suggest that the disease processes also interact mechanistically at a cellular level in a manner that exacerbates both. The elucidation of some of the mechanisms responsible for hypoperfusion in AD and for the interactions between CVD and AD has led to the identification of several novel therapeutic approaches that have the potential to ameliorate ischaemic damage and slow the progression of neurodegenerative disease.

  7. Efficacy and safety of donepezil in patients with Alzheimer's disease in assisted living facilities.

    PubMed

    Rosenblatt, Adam; Gao, Jeff; Mackell, Joan; Richardson, Sharon

    2010-09-01

    The aim of this 12-week, open-label study was to determine the safety and efficacy of donepezil in participants with Alzheimer's disease (AD) residing in assisted living facilities (ALFs). Participants received 5 mg donepezil daily for 6 weeks followed by 10 mg daily for 6 weeks. Primary and secondary outcomes were change from baseline in Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory 8 (NPI-8) scores, respectively. Safety was assessed by adverse events (AEs) and laboratory tests. Of the 97 participants, 76 completed the study. Mean MMSE score (18.7 at baseline) improved 1.8 points (P < .0001) at study end. Total NPI-8 score improved 1.8 points (P = .043). The most frequent AEs were nausea and diarrhea. Donepezil improved cognition and behavior and was safe and well tolerated. The results suggest a need for proactive screening and diagnosis of AD and support the value of treatment and use of donepezil in participants residing in ALFs.

  8. Delayed audiovisual integration of patients with mild cognitive impairment and Alzheimer's disease compared with normal aged controls.

    PubMed

    Wu, Jinglong; Yang, Jiajia; Yu, Yinghua; Li, Qi; Nakamura, Naoya; Shen, Yong; Ohta, Yasuyuki; Yu, Shengyuan; Abe, Koji

    2012-01-01

    The human brain can anatomically combine task-relevant information from different sensory pathways to form a unified perception; this process is called multisensory integration. The aim of the present study was to test whether the multisensory integration abilities of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) differed from those of normal aged controls (NC). A total of 64 subjects were divided into three groups: NC individuals (n = 24), MCI patients (n = 19), and probable AD patients (n = 21). All of the subjects were asked to perform three separate audiovisual integration tasks and were instructed to press the response key associated with the auditory, visual, or audiovisual stimuli in the three tasks. The accuracy and response time (RT) of each task were measured, and the RTs were analyzed using cumulative distribution functions to observe the audiovisual integration. Our results suggest that the mean RT of patients with AD was significantly longer than those of patients with MCI and NC individuals. Interestingly, we found that patients with both MCI and AD exhibited adequate audiovisual integration, and a greater peak (time bin with the highest percentage of benefit) and broader temporal window (time duration of benefit) of multisensory enhancement were observed. However, the onset time and peak benefit of audiovisual integration in MCI and AD patients occurred significantly later than did those of the NC. This finding indicates that the cognitive functional deficits of patients with MCI and AD contribute to the differences in performance enhancements of audiovisual integration compared with NC.

  9. Regional Coherence Changes in Alzheimer's Disease Patients with Depressive Symptoms: A Resting-State Functional MRI Study.

    PubMed

    Guo, Zhongwei; Liu, Xiaozheng; Jia, Xize; Hou, Hongtao; Cao, Yulin; Wei, Fuquan; Li, Jiapeng; Chen, Xingli; Zhang, Yingchun; Shen, Yuedi; Wei, Lili; Xu, Luoyi; Chen, Wei

    2015-01-01

    Alzheimer's disease (AD) is characterized by progressive cognitive decline along with neuropsychiatric symptoms including depression and psychosis. Depression is a common psychiatric disorder occurring in people across the lifespan. Accumulating evidence indicates that depression may be a prodrome and/or a "risk factor" for AD. However, whether AD and depression share a common pathophysiological pathway is still unclear. The aim of this study was to identify regional alterations in brain function associated with depressive symptoms in mild AD patients. Thirty-two mild AD patients were evaluated using the Neuropsychiatric Inventory and Hamilton Depression Rating Scale, and were divided into two groups: 15 AD patients with depressive symptoms (D-AD) and 17 non-depressed AD (nD-AD) patients. Using the approach of regional homogeneity (ReHo), we characterized resting-state regional brain activity in D-AD and nD-AD patients. Compared with nD-AD patients, D-AD patients showed decreased ReHo in the right precentral gyrus, right superior frontal gyrus, right middle frontal gyrus, and right inferior frontal cortex. Our findings show regional brain activity alterations in D-AD patients. Thus, D-AD pathogenesis may be attributed to abnormal neural activity in multiple brain regions.

  10. Music Therapy Using Singing Training Improves Psychomotor Speed in Patients with Alzheimer's Disease: A Neuropsychological and fMRI Study

    PubMed Central

    Satoh, Masayuki; Yuba, Toru; Tabei, Ken-ichi; Okubo, Yukari; Kida, Hirotaka; Sakuma, Hajime; Tomimoto, Hidekazu

    2015-01-01

    Background/Aims To investigate the effect of singing training on the cognitive function in Alzheimer's disease (AD) patients. Methods Ten AD patients (mean age 78.1 years) participated in music therapy using singing training once a week for 6 months (music therapy group). Each session was performed with professional musicians using karaoke and a unique voice training method (the YUBA Method). Before and after the intervention period, each patient was assessed by neuropsychological batteries, and functional magnetic resonance imaging (fMRI) was performed while the patients sang familiar songs with a karaoke device. As the control group, another 10 AD patients were recruited (mean age 77.0 years), and neuropsychological assessments were performed twice with an interval of 6 months. Results In the music therapy group, the time for completion of the Japanese Raven's Colored Progressive Matrices was significantly reduced (p = 0.026), and the results obtained from interviewing the patients' caregivers revealed a significant decrease in the Neuropsychiatric Inventory score (p = 0.042) and a prolongation of the patients' sleep time (p = 0.039). The fMRI study revealed increased activity in the right angular gyrus and the left lingual gyrus in the before-minus-after subtraction analysis of the music therapy intervention. Conclusion Music therapy intervention using singing training may be useful for dementia patients by improving the neural efficacy of cognitive processing. PMID:26483829

  11. SPECT in Alzheimer`s disease and the dementias

    SciTech Connect

    Bonte, F.J.

    1991-12-31

    Among 90 patients with a clinical diagnosis of Alzheimer`s disease (AD), two subgroups were identified for special study, including 42 patients who had a history of dementia in one or more first-degree relatives, and 14 who had a diagnosis of early AD. Of the 42 patients with a family history of dementia, 34 out of the 35 patients whose final clinical diagnosis was possible or probable AD had positive SPECT rCBF studies. Studies in the 14 patients thought to have very early AD were positive in 11 cases. This finding suggests that altered cortical physiology, and hence, rCBF, occurs quite early in the course of AD, perhaps before the onset of symptoms. It is possible that Xenon 133 rCBF studies might be used to detect the presence of subclinical AD in a population of individuals at risk to this disorder. Despite the drawbacks of a radionuclide with poor photon energy, Xenon 133, with its low cost and round-the-clock availability, deserves further study. Although the physical characteristics of Xenon 127 might make it preferable as a SPECT tracer, it is still not regularly available, and some instrument systems are not designed to handle its higher photon energies.

  12. Increased Water Diffusion in the Parcellated Cortical Regions from the Patients with Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

    PubMed

    Lin, Sung-Han; Hsu, Wen-Chuin; Ng, Shu-Hang; Cheng, Jur-Shan; Khegai, Oleksandr; Huang, Chin-Chang; Chen, Yao-Liang; Chen, Yi-Chun; Wang, Jiun-Jie

    2016-01-01

    Background: The loss of cortical neuron environment integrity is the hallmark of neurodegeneration diseases such as Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). To reveal the microenvironment changes in cerebral cortex, the current study aimed to examine the changes of mean diffusivity (MD) in parcellated brain among AD, aMCI patients and normal controls (NC). Methods: Diffusion tensor imaging data with the whole brain coverage were acquired from 28 AD (aged 69.4 ± 8.2 year old), 41 aMCI patients (aged 68.2 ± 6.4 year old) and 40 NC subjects (aged 65.7 ± 6.4 year old). Subsequently, the MD values were parcellated according to the standard automatic anatomic labeling (AAL) template. Only the 90 regions located in the cerebral cortex were used in the final analysis. The mean values of MD from each brain region were extracted and compared among the participant groups. The integrity of the white matter tracts and gray matter atrophy was analyzed using the track-based spatial statistics and voxel-based morphometry approaches, respectively. Results: Significant differences of MD were noticed both in aMCI and AD patients, in terms of the affected regions and the amount of increase. The hippocampus, parahippocampal gyrus and cingulum were the most significantly affected regions in AD patients. From all the 90 cerebral cortex regions, significant increase of MD in the AD patients was found in 40 regions, compared to only one (fusiform gyrus on the right) in aMCI patients. In the disease affected regions, the MD from aMCI patients is in state between NC and AD patients. Conclusions: Increased MD in the specific regions of the brain shows the feasibility of MD as an indicator of the early stage cortical degeneration in aMCI and AD patients.

  13. Increased Water Diffusion in the Parcellated Cortical Regions from the Patients with Amnestic Mild Cognitive Impairment and Alzheimer's Disease

    PubMed Central

    Lin, Sung-Han; Hsu, Wen-Chuin; Ng, Shu-Hang; Cheng, Jur-Shan; Khegai, Oleksandr; Huang, Chin-Chang; Chen, Yao-Liang; Chen, Yi-Chun; Wang, Jiun-Jie

    2017-01-01

    Background: The loss of cortical neuron environment integrity is the hallmark of neurodegeneration diseases such as Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). To reveal the microenvironment changes in cerebral cortex, the current study aimed to examine the changes of mean diffusivity (MD) in parcellated brain among AD, aMCI patients and normal controls (NC). Methods: Diffusion tensor imaging data with the whole brain coverage were acquired from 28 AD (aged 69.4 ± 8.2 year old), 41 aMCI patients (aged 68.2 ± 6.4 year old) and 40 NC subjects (aged 65.7 ± 6.4 year old). Subsequently, the MD values were parcellated according to the standard automatic anatomic labeling (AAL) template. Only the 90 regions located in the cerebral cortex were used in the final analysis. The mean values of MD from each brain region were extracted and compared among the participant groups. The integrity of the white matter tracts and gray matter atrophy was analyzed using the track-based spatial statistics and voxel-based morphometry approaches, respectively. Results: Significant differences of MD were noticed both in aMCI and AD patients, in terms of the affected regions and the amount of increase. The hippocampus, parahippocampal gyrus and cingulum were the most significantly affected regions in AD patients. From all the 90 cerebral cortex regions, significant increase of MD in the AD patients was found in 40 regions, compared to only one (fusiform gyrus on the right) in aMCI patients. In the disease affected regions, the MD from aMCI patients is in state between NC and AD patients. Conclusions: Increased MD in the specific regions of the brain shows the feasibility of MD as an indicator of the early stage cortical degeneration in aMCI and AD patients. PMID:28123367

  14. Cognitive and affective changes in mild to moderate Alzheimer's disease patients undergoing switch of cholinesterase inhibitors: a 6-month observational study.

    PubMed

    Spalletta, Gianfranco; Caltagirone, Carlo; Padovani, Alessandro; Sorbi, Sandro; Attar, Mahmood; Colombo, Delia; Cravello, Luca

    2014-01-01

    Patients with Alzheimer's disease after an initial response to cholinesterase inhibitors may complain a later lack of efficacy. This, in association with incident neuropsychiatric symptoms, may worsen patient quality of life. Thus, the switch to another cholinesterase inhibitor could represent a valid therapeutic strategy. The aim of this study was to investigate the effectiveness of the switch from one to another cholinesterase inhibitor on cognitive and affective symptoms in mild to moderate Alzheimer disease patients. Four hundred twenty-three subjects were included from the EVOLUTION study, an observational, longitudinal, multicentre study conducted on Alzheimer disease patients who switched to different cholinesterase inhibitor due either to lack/loss of efficacy or response, reduced tolerability or poor compliance. All patients underwent cognitive and neuropsychiatric assessments, carried out before the switch (baseline), and at 3 and 6-month follow-up. A significant effect of the different switch types was found on Mini-Mental State Examination score during time, with best effectiveness on mild Alzheimer's disease patients switching from oral cholinesterase inhibitors to rivastigmine patch. Depressive symptoms, when measured using continuous Neuropsychiatric Inventory values, decreased significantly, while apathy symptoms remained stable over the 6 months after the switch. However, frequency of both depression and apathy, when measured categorically using Neuropsychiatric Inventory cut-off scores, did not change significantly during time. In mild to moderate Alzheimer disease patients with loss of efficacy and tolerability during cholinesterase inhibitor treatment, the switch to another cholinesterase inhibitor may represent an important option for slowing cognitive deterioration. The evidence of apathy stabilization and the positive tendency of depressive symptom improvement should definitively be confirmed in double-blind controlled studies.

  15. Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology.

    PubMed

    Burgos, Kasandra; Malenica, Ivana; Metpally, Raghu; Courtright, Amanda; Rakela, Benjamin; Beach, Thomas; Shill, Holly; Adler, Charles; Sabbagh, Marwan; Villa, Stephen; Tembe, Waibhav; Craig, David; Van Keuren-Jensen, Kendall

    2014-01-01

    The discovery and reliable detection of markers for neurodegenerative diseases have been complicated by the inaccessibility of the diseased tissue--such as the inability to biopsy or test tissue from the central nervous system directly. RNAs originating from hard to access tissues, such as neurons within the brain and spinal cord, have the potential to get to the periphery where they can be detected non-invasively. The formation and extracellular release of microvesicles and RNA binding proteins have been found to carry RNA from cells of the central nervous system to the periphery and protect the RNA from degradation. Extracellular miRNAs detectable in peripheral circulation can provide information about cellular changes associated with human health and disease. In order to associate miRNA signals present in cell-free peripheral biofluids with neurodegenerative disease status of patients with Alzheimer's and Parkinson's diseases, we assessed the miRNA content in cerebrospinal fluid and serum from postmortem subjects with full neuropathology evaluations. We profiled the miRNA content from 69 patients with Alzheimer's disease, 67 with Parkinson's disease and 78 neurologically normal controls using next generation small RNA sequencing (NGS). We report the average abundance of each detected miRNA in cerebrospinal fluid and in serum and describe 13 novel miRNAs that were identified. We correlated changes in miRNA expression with aspects of disease severity such as Braak stage, dementia status, plaque and tangle densities, and the presence and severity of Lewy body pathology. Many of the differentially expressed miRNAs detected in peripheral cell-free cerebrospinal fluid and serum were previously reported in the literature to be deregulated in brain tissue from patients with neurodegenerative disease. These data indicate that extracellular miRNAs detectable in the cerebrospinal fluid and serum are reflective of cell-based changes in pathology and can be used to assess

  16. Increased frequency of T cells expressing IL-10 in Alzheimer disease but not in late-onset depression patients.

    PubMed

    Torres, Karen Cecília; Araújo Pereira, Patrícia; Lima, Giselle Sabrina; Bozzi, Isadora Cristina; Rezende, Vitor Bortolo; Bicalho, Maria Aparecida; Moraes, Edgar Nunes; Miranda, Débora Marques; Romano-Silva, Marco Aurélio

    2013-12-02

    Higher risk of dementia is expected for patients with late onset depression (LOD) history. The IL-10 polymorphisms are associated with Alzheimer disease (AD). On the other hand, there is no study associating IL-10 polymorphisms to LOD. This study aimed to investigate the -1082G/A polymorphism association in LOD, AD patients and controls and also the peripheral expression of IL-10 in CD4+ T cells. It was done in a case-control study comparing immune system phenotype and genetic polymorphism association among control individuals, LOD and AD patients. Participants were 569 subjects composed the genetics sample (249 AD, 222 LOD and 98 controls) from a tertiary medical center based on Belo Horizonte, Brazil. Flow cytometry analysis was performed in 55 people (22 AD patients, 11 LOD patients and 22 controls). A real time PCR for IL-10 SNP (rs 1800896) through genotyping analysis and flow cytometry evaluation of CD4+ T cells expressing IL-10 was done. An increased CD4+ T cells expressing IL-10 were detected only in the AD group. There was no difference detected in allele or genotype analysis for IL-10 polymorphism among LOD, AD patients or controls. IL-10 might have a role in the modulation of immune response in AD patients, however it is not presented in LOD population.

  17. The superficial white matter in Alzheimer's disease.

    PubMed

    Phillips, Owen R; Joshi, Shantanu H; Piras, Fabrizio; Orfei, Maria Donata; Iorio, Mariangela; Narr, Katherine L; Shattuck, David W; Caltagirone, Carlo; Spalletta, Gianfranco; Di Paola, Margherita

    2016-04-01

    White matter abnormalities have been shown in the large deep fibers of Alzheimer's disease patients. However, the late myelinating superficial white matter comprised of intracortical myelin and short-range association fibers has not received much attention. To investigate this area, we extracted a surface corresponding to the superficial white matter beneath the cortex and then applied a cortical pattern-matching approach which allowed us to register and subsequently sample diffusivity along thousands of points at the interface between the gray matter and white matter in 44 patients with Alzheimer's disease (Age: 71.02 ± 5.84, 16M/28F) and 47 healthy controls (Age 69.23 ± 4.45, 19M/28F). In patients we found an overall increase in the axial and radial diffusivity across most of the superficial white matter (P < 0.001) with increases in diffusivity of more than 20% in the bilateral parahippocampal regions and the temporal and frontal lobes. Furthermore, diffusivity correlated with the cognitive deficits measured by the Mini-Mental State Examination scores (P < 0.001). The superficial white matter has a unique microstructure and is critical for the integration of multimodal information during brain maturation and aging. Here we show that there are major abnormalities in patients and the deterioration of these fibers relates to clinical symptoms in Alzheimer's disease.

  18. Personalized medicine in Alzheimer's disease and depression.

    PubMed

    Souslova, Tatiana; Marple, Teresa C; Spiekerman, A Michael; Mohammad, Amin A

    2013-11-01

    Latest research in the mental health field brings new hope to patients and promises to revolutionize the field of psychiatry. Personalized pharmacogenetic tests that aid in diagnosis and treatment choice are now becoming available for clinical practice. Amyloid beta peptide biomarkers in the cerebrospinal fluid of patients with Alzheimer's disease are now available. For the first time, radiologists are able to visualize amyloid plaques specific to Alzheimer's disease in live patients using Positron Emission Tomography-based tests approved by the FDA. A novel blood-based assay has been developed to aid in the diagnosis of depression based on activation of the HPA axis, metabolic, inflammatory and neurochemical pathways. Serotonin reuptake inhibitors have shown increased remission rates in specific ethnic subgroups and Cytochrome P450 gene polymorphisms can predict antidepressant tolerability. The latest research will help to eradicate "trial and error" prescription, ushering in the most personalized medicine to date. Like all major medical breakthroughs, integration of new algorithms and technologies requires sound science and time. But for many mentally ill patients, diagnosis and effective therapy cannot happen fast enough. This review will describe the newest diagnostic tests, treatments and clinical studies for the diagnosis and treatment of Alzheimer's disease and unipolar, major depressive disorder.

  19. Reversal of cognitive decline in Alzheimer's disease

    PubMed Central

    Bredesen, Dale E.; Amos, Edwin C.; Canick, Jonathan; Ackerley, Mary; Raji, Cyrus; Fiala, Milan; Ahdidan, Jamila

    2016-01-01

    Alzheimer's disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer's disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published [1]. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had had to discontinue work were able to return to work, and those struggling at work were able to improve their performance. The patients, their spouses, and their co-workers all reported clear improvements. Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4−, who were treated with the MEND protocol for 5-24 months. The magnitude of the improvement is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective. These results have far-reaching implications for the treatment of Alzheimer's disease, MCI, and SCI; for personalized programs that may enhance pharmaceutical efficacy; and for personal identification of ApoE genotype. PMID:27294343

  20. Decrease in APP and CP mRNA expression supports impairment of iron export in Alzheimer's disease patients.

    PubMed

    Guerreiro, Cláudia; Silva, Bruno; Crespo, Ângela C; Marques, Liliana; Costa, Sónia; Timóteo, Ângela; Marcelino, Erica; Maruta, Carolina; Vilares, Arminda; Matos, Mafalda; Couto, Frederico Simões; Faustino, Paula; Verdelho, Ana; Guerreiro, Manuela; Herrero, Ana; Costa, Cristina; de Mendonça, Alexandre; Martins, Madalena; Costa, Luciana

    2015-10-01

    Alzheimer's disease (AD) is a neurodegenerative disorder of still unknown etiology and the leading cause of dementia worldwide. Besides its main neuropathological hallmarks, a dysfunctional homeostasis of transition metals has been reported to play a pivotal role in the pathogenesis of this disease. Dysregulation of iron (Fe) metabolism in AD has been suggested, particularly at the level of cellular iron efflux. Herein, we intended to further clarify the molecular mechanisms underlying Fe homeostasis in AD. In order to achieve this goal, the expression of specific Fe metabolism-related genes directly involved in Fe regulation and export was assessed in peripheral blood mononuclear cells (PBMCs) from 73AD patients and 74 controls by quantitative PCR. The results obtained showed a significant decrease in the expression of aconitase 1 (ACO1; P=0.007); ceruloplasmin (CP; P<0.001) and amyloid-beta precursor protein (APP; P=0.006) genes in AD patients compared with healthy volunteers. These observations point out to a significant downregulation in the expression of genes associated with ferroportin-mediated cellular Fe export in PBMCs from AD patients, when compared to controls. Taken together, these findings support previous studies suggesting impairment of Fe homeostasis in AD, which may lead to cellular Fe retention and oxidative stress, a typical feature of this disease.

  1. Alzheimer's as a metabolic disease.

    PubMed

    Demetrius, Lloyd A; Driver, Jane

    2013-12-01

    Empirical evidence indicates that impaired mitochondrial energy metabolism is the defining characteristic of almost all cases of Alzheimer's disease (AD). Evidence is reviewed supporting the general hypothesis that the up-regulation of OxPhos activity, a metabolic response to mitochondrial dysregulation, drives the cascade of events leading to AD. This mode of metabolic alteration, called the Inverse Warburg effect, is postulated as an essential compensatory mechanism of energy production to maintain the viability of impaired neuronal cells. This article appeals to the inverse comorbidity of cancer and AD to show that the amyloid hypothesis, a genetic and neuron-centric model of the origin of sporadic forms of AD, is not consistent with epidemiological data concerning the age-incidence rates of AD. A view of Alzheimer's as a metabolic disease-a condition consistent with mitochondrial dysregulation and the Inverse Warburg effect, will entail a radically new approach to diagnostic and therapeutic strategies.

  2. Alzheimer disease: focus on computed tomography.

    PubMed

    Reynolds, April

    2013-01-01

    Alzheimer disease is the most common type of dementia, affecting approximately 5.3 million Americans. This debilitating disease is marked by memory loss, confusion, and loss of cognitive ability. The exact cause of Alzheimer disease is unknown although research suggests that it might result from a combination of factors. The hallmarks of Alzheimer disease are the presence of beta-amyloid plaques and neurofibrillary tangles in the brain. Radiologic imaging can help physicians detect these structural characteristics and monitor disease progression and brain function. Computed tomography and magnetic resonance imaging are considered first-line imaging modalities for the routine evaluation of Alzheimer disease.

  3. Alterations in cholesterol and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease.

    PubMed

    Liu, Li; Zhang, Ke; Tan, Liang; Chen, Yu-Hua; Cao, Yun-Peng

    2015-01-01

    The aim of this study was to investigate the changes in the protein, cholesterol, and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease (AD), and identify potential blood biomarkers of the disease. A total of 31 Chinese patients with AD and 31 aged-matched control subjects were selected. Lipid rafts were isolated from platelets using Optiprep gradient centrifugation. The protein content of lipid rafts was evaluated using Micro BCA assay, the cholesterol content using molecular probes, ganglioside GM1 content using colorimetry and dot-blotting analysis. The results showed that the cholesterol and ganglioside GM1 content of lipid rafts from platelets was significantly higher in patients with AD than aged-matched control subjects, whereas the protein content of lipid rafts did not show any differences between the 2 groups. These results indicate that the increases in the cholesterol and ganglioside GM1 content of lipid rafts from the platelets of patients with AD might serve as a biochemical adjunct to the clinical diagnosis of AD.

  4. Association studies in late onset sporadic Alzheimer`s disease

    SciTech Connect

    Goate, A.M.; Lendon, C.; Talbot, C.

    1994-09-01

    Alzheimer`s disease (AD) is characterized by an adult onset progressive dementia and the presence of numerous plaques and tangles within the brain at autopsy. The senile plaques are composed of a proteinaceous core surrounded by dystrophic neurites. The major protein component of the core is {beta}-amyloid but antibodies to many other proteins bind to senile plaques, e.g., antibodies to apolioprotein E (ApoE) and to {alpha}1-antichymotrypsin (AACT). Genetic studies have implicated mutations within the {beta}-amyloid precursor protein gene as the cause of AD in a small number of early onset AD families. More recently, assocition studies in late onset AD have demonstrated a positive association between ApoE-{epsilon}4 and AD. We report evidence for a negative association between ApoE-{epsilon}2 and AD in a large sample of sporadic late onset AD cases and matched controls supporting the role of ApoE in the etiology of AD. Ninety-three patients with sporadic AD (average age = 75 years, s.d. 8 yrs.) and 67 normal controls from the same ethnic background (age = 77 yrs., s.d. 10 yrs.) were recruited through the patient registry of the Washington University Alzheimer`s Disease Research Center. We found a statistically significant increase in ApoE-{epsilon}4 allele frequency in patients compared with controls ({chi}{sup 2}=7.75, 1 d.f., one tailed p=0.0027) and a significant decrease in {epsilon}2 allele frequency (Fisher`s exact test, one tailed p=0.0048), whereas the decreased frequency of {epsilon}3 in the patient groups was not statistically significant. Allele {epsilon}2 conferred a strong protective effect in our sample, with the odds ratio for AD for subjects possessing this allele being 0.08 (85% confidence interval 0.01-0.69). Similar studies using a polymorphism within the AACT gene showed no association with alleles at this locus in the entire AD sample or in AD cases homozygous for ApoE-{epsilon}3.

  5. Alzheimer's disease: risk and protection.

    PubMed

    Jorm, A F

    1997-10-20

    Only four risk factors for Alzheimer's disease can be regarded as confirmed--old age, family history of dementia, apo-E genotype and Down syndrome. Other disputed risk factors with some supporting evidence include ethnic group, head trauma and aluminium in drinking water. Possible protection factors, such as anti-inflammatory drugs, oestrogen replacement therapy and a high education level, are of great interest because they suggest possible preventive action.

  6. Cellular basis of Alzheimer's disease.

    PubMed

    Bali, Jitin; Halima, Saoussen Ben; Felmy, Boas; Goodger, Zoe; Zurbriggen, Sebastian; Rajendran, Lawrence

    2010-12-01

    Alzheimer's disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD.

  7. Degree of ambulation and factors associated with the median distance moved per day in Alzheimer's disease patients.

    PubMed

    Nishikata, Shiori; Yamakawa, Miyae; Shigenobu, Kazue; Suto, Shunji; Makimoto, Kiyoko

    2013-09-01

    The Integrated Circuit tag monitoring system became available to measure wandering in terms of the distance moved by dementia patients. The purposes of the study were to describe degree of ambulation in patients with Alzheimer's disease (AD) and to examine factors associated with the distance moved. AD patients were recruited at a dementia care unit in Asakayama Hospital, Osaka, Japan. The monitoring system generated the distance moved per day. Demographic and clinical data were abstracted from medical records. Mini-Mental State Examination was used to measure cognitive function. A multiple linear regression was used to predict the distance moved per day. The research was approved by the ethics committee of the university and the hospital, and written informed consent was obtained from the patients' proxies. Majority of the AD subjects monitored had moderate to advance stage of dementia. Patients' age and cognitive function were predictors of the median distance moved/day, and these two variables explained almost half of the variance. Older age and lower cognitive function were associated with reduced median distance moved per day in AD patients.

  8. DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease.

    PubMed

    Yuki, Dai; Sugiura, Yuki; Zaima, Nobuhiro; Akatsu, Hiroyasu; Takei, Shiro; Yao, Ikuko; Maesako, Masato; Kinoshita, Ayae; Yamamoto, Takayuki; Kon, Ryo; Sugiyama, Keikichi; Setou, Mitsutoshi

    2014-11-20

    Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by senile plaques, neurofibrillary tangles, synaptic disruption, and neuronal loss. Several studies have demonstrated decreases of docosahexaenoic acid-containing phosphatidylcholines (DHA-PCs) in the AD brain. In this study, we used matrix-assisted laser desorption/ionization imaging mass spectrometry in postmortem AD brain to show that PC molecular species containing stearate and DHA, namely PC(18:0/22:6), was selectively depleted in the gray matter of patients with AD. Moreover, in the brain regions with marked amyloid β (Aβ) deposition, the magnitude of the PC(18:0/22:6) reduction significantly correlated with disease duration. Furthermore, at the molecular level, this depletion was associated with reduced levels of the postsynaptic protein PSD-95 but not the presynaptic protein synaptophysin. Interestingly, this reduction in PC(18:0/22:6) levels did not correlate with the degrees of Aβ deposition and neuronal loss in AD. The analysis of the correlations of key factors and disease duration showed that their effects on the disease time course were arranged in order as Aβ deposition, presynaptic disruption, postsynaptic disruption coupled with PC(18:0/22:6) reduction, and neuronal loss.

  9. DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease

    PubMed Central

    Yuki, Dai; Sugiura, Yuki; Zaima, Nobuhiro; Akatsu, Hiroyasu; Takei, Shiro; Yao, Ikuko; Maesako, Masato; Kinoshita, Ayae; Yamamoto, Takayuki; Kon, Ryo; Sugiyama, Keikichi; Setou, Mitsutoshi

    2014-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by senile plaques, neurofibrillary tangles, synaptic disruption, and neuronal loss. Several studies have demonstrated decreases of docosahexaenoic acid-containing phosphatidylcholines (DHA-PCs) in the AD brain. In this study, we used matrix-assisted laser desorption/ionization imaging mass spectrometry in postmortem AD brain to show that PC molecular species containing stearate and DHA, namely PC(18:0/22:6), was selectively depleted in the gray matter of patients with AD. Moreover, in the brain regions with marked amyloid β (Aβ) deposition, the magnitude of the PC(18:0/22:6) reduction significantly correlated with disease duration. Furthermore, at the molecular level, this depletion was associated with reduced levels of the postsynaptic protein PSD-95 but not the presynaptic protein synaptophysin. Interestingly, this reduction in PC(18:0/22:6) levels did not correlate with the degrees of Aβ deposition and neuronal loss in AD. The analysis of the correlations of key factors and disease duration showed that their effects on the disease time course were arranged in order as Aβ deposition, presynaptic disruption, postsynaptic disruption coupled with PC(18:0/22:6) reduction, and neuronal loss. PMID:25410733

  10. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer's Disease.

    PubMed

    Gaser, Christian; Franke, Katja; Klöppel, Stefan; Koutsouleris, Nikolaos; Sauer, Heinrich

    2013-01-01

    Alzheimer's disease (AD), the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI)-based biomarker that predicts the individual progression of mild cognitive impairment (MCI) to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE) score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%). The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF). With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07-1.13]). Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options.

  11. Rodent models of neuroinflammation for Alzheimer's disease.

    PubMed

    Nazem, Amir; Sankowski, Roman; Bacher, Michael; Al-Abed, Yousef

    2015-04-17

    Alzheimer's disease remains incurable, and the failures of current disease-modifying strategies for Alzheimer's disease could be attributed to a lack of in vivo models that recapitulate the underlying etiology of late-onset Alzheimer's disease. The etiology of late-onset Alzheimer's disease is not based on mutations related to amyloid-β (Aβ) or tau production which are currently the basis of in vivo models of Alzheimer's disease. It has recently been suggested that mechanisms like chronic neuroinflammation may occur prior to amyloid-β and tau pathologies in late-onset Alzheimer's disease. The aim of this study is to analyze the characteristics of rodent models of neuroinflammation in late-onset Alzheimer's disease. Our search criteria were based on characteristics of an idealistic disease model that should recapitulate causes, symptoms, and lesions in a chronological order similar to the actual disease. Therefore, a model based on the inflammation hypothesis of late-onset Alzheimer's disease should include the following features: (i) primary chronic neuroinflammation, (ii) manifestations of memory and cognitive impairment, and (iii) late development of tau and Aβ pathologies. The following models fit the pre-defined criteria: lipopolysaccharide- and PolyI:C-induced models of immune challenge; streptozotocin-, okadaic acid-, and colchicine neurotoxin-induced neuroinflammation models, as well as interleukin-1β, anti-nerve growth factor and p25 transgenic models. Among these models, streptozotocin, PolyI:C-induced, and p25 neuroinflammation models are compatible with the inflammation hypothesis of Alzheimer's disease.

  12. The Influence of Background Music on the Performance of the Mini Mental State Examination with Patients Diagnosed with Alzheimer's Disease.

    PubMed

    Silber

    1999-01-01

    The purpose of this study was to determine whether background music had an influence on the scores of patients with Alzheimer's disease during the Mini Mental State Examination (MMS). Eighteen patients diagnosed with dementia from a day care center participated in the study. Eleven (experimental group) were examined 3 times, each time 1 month apart. The first examination, called pretest, served as a baseline and was done without background music. The second and third examinations (test and posttest) were done with background music. Seven people (control group) were examined 3 times, each time one-month apart. The three tests (pretest, test, posttest) were done without background music. The Wilcoxon matched-pairs test was used to compare the results within each group. No significant differences were found between the three tests for both groups. The Mann-Whitney test was used to compare the results between the experimental and control groups. No significant differences were found between these two groups. This suggests that background music used with persons affected by dementia at this second stage of the disease plays a neutral role during the MMS. Another suggestion is that perhaps people at this stage of the disease do not feel any stress or threat that may have an impact on their concentration during the MMS. Other suggestions are made for possible further research.

  13. Cerebrospinal fluid levels of tau phosphorylated at threonine 181 in patients with Alzheimer's disease and vascular dementia.

    PubMed

    Ravaglia, Sabrina; Bini, Paola; Sinforiani, Elena; Franciotta, Diego; Zardini, Elisabetta; Tosca, Pietro; Moglia, Arrigo; Costa, Alfredo

    2008-12-01

    In 31 patients with probable Alzheimer's disease (AD), 19 with probable vascular dementia (VaD) and 20 with Possible AD and Possible VaD, cerebrospinal fluid (CSF) tau levels hyperphosphorylated at threonine 181 (Ptau) were measured by ELISA. Thirty-six age-matched subjects were used as controls. The severity of the cognitive decline was assessed at the time of CSF analysis and after a 12-month follow-up. The groups had comparable age, degree of cognitive impairment and disease duration; these parameters were not related to P-tau levels. P-tau discriminated between demented patients and controls, but no significant difference emerged between AD and the other groups. By contrast, higher P-tau values were found to predict, independently of the clinical diagnosis, a more rapid evolution of cognitive decline. Whether these findings are due to a lack of CSF P-tau specificity or to the low reliability of clinical and radiological criteria remains unclear. P-tau may be useful in the evaluation of disease evolution, by predicting the rate of cognitive decline.

  14. Vaccination against Alzheimer disease: an update on future strategies.

    PubMed

    Fettelschoss, Antonia; Zabel, Franziska; Bachmann, Martin F

    2014-01-01

    Alzheimer disease is a devastating chronic disease without adequate therapy. More than 10 years ago, it was demonstrated in transgenic mouse models that vaccination may be a novel, disease-modifying therapy for Alzheimer. Subsequent clinical development has been a roller-coaster with some positive and many negative news. Here, we would like to summarize evidence that next generation vaccines optimized for old people and focusing on patients with mild disease stand a good chance to proof efficacious for the treatment of Alzheimer.

  15. Alzheimer's Disease Facts and Figures

    MedlinePlus

    ... a rate twice as high. Invest in a world without Alzheimer's. Donate Caregivers In 2016, 15.9 ... Association ® . All rights reserved. Our vision is a world without Alzheimer's Formed in 1980, the Alzheimer's Association ...

  16. Normal Hearing Ability but Impaired Auditory Selective Attention Associated with Prediction of Response to Donepezil in Patients with Alzheimer's Disease

    PubMed Central

    Ouchi, Yoshitaka; Meguro, Kenichi; Akanuma, Kyoko; Kato, Yuriko; Yamaguchi, Satoshi

    2015-01-01

    Background. Alzheimer's disease (AD) patients have a poor response to the voices of caregivers. After administration of donepezil, caregivers often find that patients respond more frequently, whereas they had previously pretended to be “deaf.” We investigated whether auditory selective attention is associated with response to donepezil. Methods. The subjects were40 AD patients, 20 elderly healthy controls (HCs), and 15 young HCs. Pure tone audiometry was conducted and an original Auditory Selective Attention (ASA) test was performed with a MoCA vigilance test. Reassessment of the AD group was performed after donepezil treatment for 3 months. Results. Hearing level of the AD group was the same as that of the elderly HC group. However, ASA test scores decreased in the AD group and were correlated with the vigilance test scores. Donepezil responders (MMSE 3+) also showed improvement on the ASA test. At baseline, the responders had higher vigilance and lower ASA test scores. Conclusion. Contrary to the common view, AD patients had a similar level of hearing ability to healthy elderly. Auditory attention was impaired in AD patients, which suggests that unnecessary sounds should be avoided in nursing homes. Auditory selective attention is associated with response to donepezil in AD. PMID:26161001

  17. Assessing the impact and social perception of self-regulated music stimulation with patients with Alzheimer's disease.

    PubMed

    Lancioni, Giulio E; O'Reilly, Mark F; Singh, Nirbhay N; Sigafoos, Jeff; Grumo, Gianluca; Pinto, Katia; Stasolla, Fabrizio; Signorino, Mario; Groeneweg, Jop

    2013-01-01

    We assessed the impact and social rating of an active and a passive music condition implemented with six patients with Alzheimer's disease. In the active condition, the patients used a simple hand response and a microswitch to self-regulate music stimulation inputs. In the passive condition, music stimulation was automatically presented throughout the sessions. Active and passive stimulation sessions were preceded and followed by control (non-stimulation) sessions. The active condition sessions showed an increase in the patients' indices of positive participation (e.g., singing or music-related movements, and smiles) greater than that observed in the passive condition sessions for five of the six patients. Positive intervention effects could also spread to the post-intervention sessions. Social raters (42 care and rehabilitation staff members working with persons with multiple disabilities) favored the active condition on a six-item questionnaire dealing with, among others, conditions' suitability, respect of patients' dignity and independence, and practicality. The implications of the findings as to the plausibility/desirability of an active stimulation condition were discussed.

  18. Successful Fitting of a Complete Maxillary Denture in a Patient with Severe Alzheimer's Disease Complicated by Oral Dyskinesia

    PubMed Central

    Hashimoto, Akie; Inoue, Ryosuke; Yoshimoto, Shohei; Hirofuji, Takao

    2016-01-01

    There is an increasing population of elderly patients suffering from Alzheimer's disease (AD), the most common form of dementia. In dentistry, a critical problem associated with these patients is the use of a new denture, as AD patients often refuse dental management and are disturbed by minor changes in their oral environment. Some AD patients have further complications associated with oral dyskinesia, a movement disorder that can make dental management difficult, including the stability of a complete denture. In this case, we successfully fitted a complete maxillary denture using modified bilateral balanced occlusion after multiple tooth extractions under intravenous sedation in a 66-year-old woman with severe AD complicated by oral dyskinesia. Following treatment, her appetite and food intake greatly improved. Providing a well-fitting complete denture applied by modified bilateral balanced occlusion, which removes lateral interference using zero-degree artificial teeth for movement disorder of the jaw in patients with severe AD complicated by oral dyskinesia, helps improve oral function. PMID:27822393

  19. Frontal Lobe Function and Risk of Hip Fracture in Patient With Alzheimer Disease: An Analysis of Linked Data.

    PubMed

    Roh, Hyun Woong; Hong, Chang Hyung; Lee, SooJin; Lee, Yunhwan; Lee, Kang Soo; Chang, Ki Jung; Oh, Byoung Hoon; Choi, Seong Hye; Kim, Seong Yoon; Back, Joung Hwan; Chung, Young Ki; Lim, Ki Young; Noh, Jai Sung; Son, Sang Joon

    2015-11-01

    To determine the association between frontal lobe function and risk of hip fracture in patients with Alzheimer disease (AD).Retrospective cohort study using multicenter hospital-based dementia registry and national health insurance claim data was done. Participants who had available data of neuropsychological test, national health insurance claim, and other covariates were included. A total of 1660 patients with AD were included based on Stroop Test results. A total of 1563 patients with AD were included based on the Controlled Oral Word Association Test (COWAT) results. Hip fracture was measured by validated identification criteria using national health insurance claim data. Frontal lobe function was measured by Stroop Test and COWAT at baseline.After adjusting for potential covariates, including cognitive function in other domains (language, verbal and nonverbal memory, and attention), the Cox proportional hazard regression analysis revealed that risk of a hip fracture was decreased with a hazard ratio (HR) of 0.98 per one point of increase in the Stroop Test (adjusted HR = 0.98, 95% confidence interval [CI]: 0.97-1.00) and 0.93 per one point increase in COWAT (adjusted HR = 0.93, 95% CI: 0.88-0.99).The risk of hip fracture in AD patients was associated with baseline frontal lobe function. The result of this research presents evidence of association between frontal lobe function and risk of hip fracture in patients with AD.

  20. Diminished glucose transport and phosphorylation in Alzheimer`s disease determined by dynamic FDG-PET

    SciTech Connect

    Piert, M.; Koeppe, R.A.; Giordani, B.; Berent, S.; Kuhl, D.E.

    1996-02-01

    Using dynamic [{sup 18}F] fluorodeoxyglucose (FDG) and PET, kinetic rate constants that describe influx (K{sub 1}) and efflux (k{sub 2}) of FDG as well s phosphorylation (k{sub 3}) and dephosphorylation (k{sub 4}) were determined in patients with probable Alzheimer`s disease and similarly aged normal controls. The regional cerebral metabolic rate for glucose (CMR{sub glu}) was calculated from individually fitted rate constants in frontal, temporal, parietal and occipital cerebral cortex, caudate nucleus, putamen, thalamus and cerebellar cortex. Dynamic PET scans were obtained in normal controls (n = 10, mean age = 67) and Alzheimer`s disease patients (n = 8, mean age = 67) for 60 min following injection of 10 mCi of FDG. The Alzheimer`s disease group was characterized by decreases of the CMR{sub glu} ranging from 13.3% in the frontal to 40.9% in the parietal cortex, which achieved significance in all regions except the thalamus. K{sub 1} was significantly reduced in the parietal (p < 0.01) and temporal cortices (p < 0.005), temporal and occipital cortex, and in the putamen and cerebellum (p < 0.05). The rate constants k{sub 2} and k{sub 4} were unchanged in the Alzheimer`s disease group. These data suggest that hypometabolism in Alzheimer`s disease is related to reduced glucose phosphorylation activity as well as diminished glucose transport, particularly in the most metabolically affected areas of the brain, the parietal and temporal cortex. 60 refs., 2 figs., 2 tabs.

  1. Individual Patient Research (IPR) Outcomes with Alzheimer's Disease: The Psycho-neuro-immune Viewpoint

    PubMed Central

    Chiappelli, Francesco; Khakshooy, Allen

    2016-01-01

    Traditional research in the health sciences has involved control and experimental groups of patients, and descriptive and inferential statistical analyses performed on the measurements obtained from the samples in each group. As the novel model of translational healthcare, which integrates translational research and translational effectiveness, becomes increasingly established in modern contemporary medicine, healthcare continues to evolve into a model of care that is evidence-based, effectiveness-focused and patientcentered. Patient-centered care requires the timely and critical development and validation of a new research paradigm, which is referred to as “individual patient research (IPR)”, as opposed as the customary group research approach. That is to say, research in geriatric disease conditions, such as Alzheimer’s Disease (AD) must be performed from the viewpoint of individual patient research outcomes, and individual patient data analysis. Here, we discuss IPR in patients with AD in the context of the best available research evidence that indicates psychological symptoms, endocrine deregulation, and immune alterations in AD. We propose a clinical adaptive cluster randomized stepped wedge blinded controlled trial, with sequential with sequential roll-out of an evidence-based intervention in a crossover paradigm. PMID:28246459

  2. IFN-γ and TNF-α are involved during Alzheimer disease progression and correlate with nitric oxide production: a study in Algerian patients.

    PubMed

    Belkhelfa, Mourad; Rafa, Hayet; Medjeber, Oussama; Arroul-Lammali, Amina; Behairi, Nassima; Abada-Bendib, Myriam; Makrelouf, Mohamed; Belarbi, Soreya; Masmoudi, Ahmed Nacer; Tazir, Meriem; Touil-Boukoffa, Chafia

    2014-11-01

    Alzheimer's disease (AD) is a neurodegenerative disease leading to a progressive and irreversible loss of mental functions. It is characterized by 3 stages according to the evolution and the severity of the symptoms. This disease is associated with an immune disorder, which appears with significant rise in the inflammatory cytokines and increased production of free radicals such as nitric oxide (NO). Our study aims to investigate interferon (IFN)-γ and tumor necrosis factor-α (TNF-α) involvement in NO production, in vivo and ex vivo, in peripheral blood mononuclear cells from Algerian patients (n=25), according to the different stages of the disease (mild Alzheimer's, moderate Alzheimer's, and severe Alzheimer's) in comparison to mild cognitive impairment (MCI) patients. Interestingly, we observed that in vivo IFN-γ and TNF-α levels assessed in patients with AD in mild and severe stages, respectively, are higher than those observed in patients with moderate stage and MCI. Our in vivo and ex vivo results show that NO production is related to the increased levels of IFN-γ and TNF-α, in mild and severe stages of AD. Remarkably, significant IFN-γ level is only detected in mild stage of AD. Our study suggests that NO production is IFN-γ dependent both in MCI and mild Alzheimer's patients. Further, high levels of NO are associated with an elevation of TNF-α levels in severe stage of AD. Collectively, our data indicate that the proinflammatory cytokine production seems, in part, to be involved in neurological deleterious effects observed during the development of AD through NO pathway.

  3. Tau immunotherapy for Alzheimer's disease.

    PubMed

    Pedersen, Jan Torleif; Sigurdsson, Einar M

    2015-06-01

    Targeting pathological tau protein in Alzheimer's disease (AD) and related tauopathies has shown great potential in animal models. Given that tau lesions correlate better with the degree of dementia than do amyloid-β (Aβ) plaques, their clearance may be clinically more efficacious than removing Aβ when cognitive deficits become evident in AD. Several complementary mechanisms of antibody-mediated removal of tau aggregates are likely to act in concert and the importance of each one may depend on antibody properties, the disease, and its stage. Clinical trials of tau immunotherapy are already underway and several more are likely to be initiated in the near future.

  4. [Alzheimer's disease: New therapeutic strategies].

    PubMed

    Villegas, Sandra

    2015-07-20

    The rapid increase in prevalence rates of Alzheimer's disease means that treatments to prevent, stop or reverse this devastating disease are urgently needed. Despite advances in understanding its molecular pathology, there are no drugs that can halt its progression. This review takes a tour through phase 2, or higher studies, probing receptor agonist agents interfering with aggregation, inhibitors/modulators of secretases, lipid-lowering agents, and, finally and most extensively, immunotherapy. The fact that phase 3 studies with bapineuzumab and solaneuzumab have recently failed does not invalidate the potential of immunotherapy, as more information is available and new clinical trials are being initiated.

  5. Exercise for the diabetic brain: how physical training may help prevent dementia and Alzheimer's disease in T2DM patients.

    PubMed

    Bertram, Sebastian; Brixius, Klara; Brinkmann, Christian

    2016-08-01

    Epidemiological studies indicate that patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing dementia/Alzheimer's disease (AD). This review, which is based on recent studies, presents a molecular framework that links the two diseases and explains how physical training could help counteract neurodegeneration in T2DM patients. Inflammatory, oxidative, and metabolic changes in T2DM patients cause cerebrovascular complications and can lead to blood-brain-barrier (BBB) breakdown. Peripherally increased pro-inflammatory molecules can then pass the BBB more easily and activate stress-activated pathways, thereby promoting key pathological features of dementia/AD such as brain insulin resistance, mitochondrial dysfunction, and accumulation of neurotoxic beta-amyloid (Aβ) oligomers, leading to synaptic loss, neuronal dysfunction, and cell death. Ceramides can also pass the BBB, induce pro-inflammatory reactions, and disturb brain insulin signaling. In a vicious circle, oxidative stress and the pro-inflammatory environment intensify, leading to further cognitive decline. Low testosterone levels might be a common risk factor in T2DM and AD. Regular physical exercise reinforces antioxidative capacity, reduces oxidative stress, and has anti-inflammatory effects. It improves endothelial function and might increase brain capillarization. Physical training can further counteract dyslipidemia and reduce increased ceramide levels. It might also improve Aβ clearance by up-regulating Aβ transporters and, in some cases, increase basal testosterone levels. In addition, regular physical activity can induce neurogenesis. Physical training should therefore be emphasized as a part of prevention programs developed for diabetic patients to minimize the risk of the onset of neurodegenerative diseases among this specific patient group.

  6. Toward a brain-computer interface for Alzheimer's disease patients by combining classical conditioning and brain state classification.

    PubMed

    Liberati, Giulia; Dalboni da Rocha, Josué Luiz; van der Heiden, Linda; Raffone, Antonino; Birbaumer, Niels; Olivetti Belardinelli, Marta; Sitaram, Ranganatha

    2012-01-01

    Brain-computer interfaces (BCIs) provide alternative methods for communicating and acting on the world, since messages or commands are conveyed from the brain to an external device without using the normal output pathways of peripheral nerves and muscles. Alzheimer's disease (AD) patients in the most advanced stages, who have lost the ability to communicate verbally, could benefit from a BCI that may allow them to convey basic thoughts (e.g., "yes" and "no") and emotions. There is currently no report of such research, mostly because the cognitive deficits in AD patients pose serious limitations to the use of traditional BCIs, which are normally based on instrumental learning and require users to self-regulate their brain activation. Recent studies suggest that not only self-regulated brain signals, but also involuntary signals, for instance related to emotional states, may provide useful information about the user, opening up the path for so-called "affective BCIs". These interfaces do not necessarily require users to actively perform a cognitive task, and may therefore be used with patients who are cognitively challenged. In the present hypothesis paper, we propose a paradigm shift from instrumental learning to classical conditioning, with the aim of discriminating "yes" and "no" thoughts after associating them to positive and negative emotional stimuli respectively. This would represent a first step in the development of a BCI that could be used by AD patients, lending a new direction not only for communication, but also for rehabilitation and diagnosis.

  7. Neural restrictive silencer factor and choline acetyltransferase expression in cerebral tissue of Alzheimer's Disease patients: A pilot study.

    PubMed

    González-Castañeda, Rocío E; Sánchez-González, Víctor J; Flores-Soto, Mario; Vázquez-Camacho, Gonzalo; Macías-Islas, Miguel A; Ortiz, Genaro G

    2013-03-01

    Decreased Choline Acetyltransferase (ChAT) brain level is one of the main biochemical disorders in Alzheimer's Disease (AD). In rodents, recent data show that the CHAT gene can be regulated by a neural restrictive silencer factor (NRSF). The aim of the present work was to evaluate the gene and protein expression of CHAT and NRSF in frontal, temporal, entorhinal and parietal cortices of AD patient brains. Four brains from patients with AD and four brains from subjects without dementia were studied. Cerebral tissues were obtained and processed by the guanidine isothiocyanate method for RNA extraction. CHAT and NRSF gene and protein expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. CHAT gene expression levels were 39% lower in AD patients as compared to the control group (p < 0.05, U test). ChAT protein levels were reduced by 17% (p = 0.02, U test). NRSF gene expression levels were 86% higher in the AD group (p = 0.001, U test) as compared to the control group. In the AD subjects, the NRSF protein levels were 57% higher (p > 0.05, U test) than in the control subjects. These findings suggest for the first time that in the brain of AD patients high NRSF protein levels are related to low CHAT gene expression levels.

  8. Pharmacotherapeutic targets in Alzheimer's disease

    PubMed Central

    Biran, Yif'at; Masters, Colin L; Barnham, Kevin J; Bush, Ashley I; Adlard, Paul A

    2009-01-01

    Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder which is characterized by an increasing impairment in normal memory and cognitive processes that significantly diminishes a person's daily functioning. Despite decades of research and advances in our understanding of disease aetiology and pathogenesis, there are still no effective disease-modifying drugs available for the treatment of AD. However, numerous compounds are currently undergoing pre-clinical and clinical evaluations. These candidate pharma-cotherapeutics are aimed at various aspects of the disease, such as the microtubule-associated τ-protein, the amyloid-β (Aβ) peptide and metal ion dyshomeostasis – all of which are involved in the development and progression of AD. We will review the way these pharmacological strategies target the biochemical and clinical features of the disease and the investigational drugs for each category. PMID:19040415

  9. Relationship of aluminum to Alzheimer's disease.

    PubMed Central

    Perl, D P

    1985-01-01

    Alzheimer's disease is a progressive degenerative brain disease of unknown etiology, characterized by the development of large numbers of neurofibrillary tangles and senile plaques in the brain. Aluminum salts may be used experimentally to produce lesions which are similar, but not identical, to the neurofibrillary tangle. Although some studies have reported increased amounts of aluminum in the brains of Alzheimer's disease victims, these bulk analysis studies have been difficult to replicate and remain controversial. Using scanning electron microscopy with X-ray spectrometry, we have investigated this question on the cellular level. We have identified abnormal accumulations of aluminum within neurons derived from Alzheimer's disease patients containing neurofibrillary tangles. Similar accumulations have been detected in the numerous neurofibrillary tangle-bearing neurons seen in the brains of the indigenous native population of the island of Guam who suffer from amyotrophic lateral sclerosis and parkinsonism with dementia. Epidemiologic evidence strongly suggests a causal role for local environmental conditions relating to availability of aluminum, calcium, and magnesium. In view of the fact that a major consequence of acid rain is the liberation of large amounts of aluminum in bioavailable forms, concerns are raised about possible human health risks of this environmental phenomenon. PMID:4076080

  10. Preventing schizophrenia and Alzheimer disease: comparative ethics.

    PubMed

    Post, S G

    2001-08-01

    Schizophrenia and Alzheimer disease are both diseases of the brain that involve genetic susceptibility factors and for which the prevention or delay of symptom onset are important research goals. This paper provides some comparisons between current preventive efforts in schizophrenia and Alzheimer disease, focusing on certain ethical features of these endeavors such as potential discrimination, misdiagnosis, and stigma.

  11. 7 Warning Signs of Alzheimer's | Alzheimer's disease | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Alzheimer's Disease 7 Warning Signs of Alzheimer's Past Issues / Fall ... the public to the early warning signs of Alzheimer's disease. If someone has several or even most of ...

  12. Estrogen Intake and Copper Depositions: Implications for Alzheimer's Disease?

    PubMed Central

    Amtage, Florian; Birnbaum, Dzelila; Reinhard, Thomas; Niesen, Wolf-Dirk; Weiller, Cornelius; Mader, Irina; Meyer, Philipp T.; Rijntjes, Michel

    2014-01-01

    We present a patient with chronic postmenopausal estrogen intake with presence of Kayser-Fleischer ring in the cornea and Alzheimer's disease and discuss the pathophysiological mechanisms of estrogen intake and copper accumulation in various tissues, including the central nervous system. Sonography was compatible with copper accumulation in the basal ganglia, but the patient showed no clinical signs of Wilson's disease. Magnetic resonance imaging and positron emission tomography revealed a typical pattern for Alzheimer's disease. We propose increased copper levels as a direct effect of estrogen intake due to an augmented ATP7A-mRNA in the intestine. Moreover, we discuss the impact of elevated free serum copper on accompanying Alzheimer's disease, knowing that copper plays a crucial role in the formation of amyloid plaques and tau aggregation. This might offer a partial explanation for the observation that postmenopausal estrogen therapy is associated with a higher risk of mild cognitive impairment and Alzheimer's disease. PMID:25076894

  13. Allelic association at the D14S43 locus in early onset Alzheimer`s disease

    SciTech Connect

    Brice, A.; Tardieu, S.; Campion, D.; Martinez, M.

    1995-04-24

    The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer`s disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer`s disease (<60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelic association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample. 16 refs., 2 tabs.

  14. Neural stem cells and Alzheimer's disease: challenges and hope.

    PubMed

    Zhongling Feng; Gang Zhao; Lei Yu

    2009-01-01

    Alzheimer's disease is characterized by degeneration and dysfunction of synapses and neurons in brain regions critical for learning and memory functions. The endogenous generation of new neurons in certain regions of the mature brain, derived from primitive cells termed neural stem cells, has raised hope that neural stem cells may be recruited for structural brain repair. Stem cell therapy has been suggested as a possible strategy for replacing damaged circuitry and restoring learning and memory abilities in patients with Alzheimer's disease. In this review, we outline the promising investigations that are raising hope, and understanding the challenges behind translating underlying stem cell biology into novel clinical therapeutic potential in Alzheimer's disease.

  15. Combination therapy of donepezil and vitamin E in Alzheimer disease.

    PubMed

    Klatte, Emily T; Scharre, Douglas W; Nagaraja, Haikady N; Davis, Rebecca A; Beversdorf, David Q

    2003-01-01

    A retrospective chart review was performed on 130 patients from the Ohio State University Memory Disorders Clinic to examine the long-term effects of combination therapy with donepezil and vitamin E on patients with Alzheimer disease. Subjects were included if they met National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer disease, had taken at least 5 mg donepezil and at least 1000 U vitamin E daily, had at least a 1-year follow-up while continuing these medications, and had a Mini-Mental State Examination score of 10-24. The Mini-Mental State Examination was then recorded annually thereafter. These data were compared with the Consortium to Establish a Registry for Alzheimer's Disease database for patients collected prior to the availability of these treatment options. Patients declined at a significantly lower rate as compared with the Consortium to Establish a Registry for Alzheimer's Disease data. The long-term combination therapy of donepezil and vitamin E appears beneficial for patients with Alzheimer disease. Future prospective studies would be needed to compare combination treatment to vitamin E and donepezil alone.

  16. Interventions for Caregivers of Patients with Alzheimer's Disease: A Review and Analysis of Content, Process, and Outcomes.

    ERIC Educational Resources Information Center

    Bourgeois, Michelle S.; And Others

    1996-01-01

    Examines the content and process of Alzheimer's disease caregiver interventions. Describes the types of interventions currently in use and factors affecting intervention outcomes. Concludes with specific recommendations for the application of intervention technology and for the documentation of intervention research. (KW)

  17. Trajectories of Preparation for Future Care among First-Degree Relatives of Alzheimer's Disease Patients: An Ancillary Study of ADAPT

    ERIC Educational Resources Information Center

    Mak, Wingyun; Sorensen, Silvia

    2012-01-01

    Purpose: This study examines the longitudinal patterns of Preparation for Future Care (PFC), defined as Awareness, Avoidance, Gathering Information, Decision Making, and Concrete Plans, in first-degree relatives of people with Alzheimer's disease (AD). Design and Methods: Eight time points across 6.5 years from a subsample of adults aged 70 years…

  18. Study on a quantitative electroencephalography power spectrum typical of Chinese Han Alzheimer's disease patients by using wavelet transforms

    NASA Astrophysics Data System (ADS)

    Wan, Baikun; Ming, Dong; Fu, Xiaomeng; Yang, Chunmei; Qi, Hongzhi; Chen, Binjin

    2006-03-01

    Our objective was to investigate the quantitative electroencephalogram (EEG) power spectrum typical of Chinese Han ethnic Alzheimer's disease (AD) patients. A study on the resting EEG was carried out on 103 local AD (NINCDS-ADRDA criteria) patients, and 124 age-matched normal elderly subjects served as controls. A novel multi-resolution decomposition algorithm based on Daubechies wavelet transform was employed for EEG spectral analysis. This algorithm decomposed recorded EEG signals into components with five frequency subbands, which especially provided more electroneural activity details in comparison with the conventional four subbands. A significant prevalence of an EEG spectrum characterized by increased slow activity with decreased fast activity was found in these patients. Moreover, the spectral power increase/decrease was mainly centralized in the below-2 Hz/over-8 Hz band, whereas the 2-8 Hz band did not show any widespread change. In conclusion, this study may provide some evidence of specific spectral changes of EEG affected by AD in China.

  19. Label-Free Quantitative Immunoassay of Fibrinogen in Alzheimer Disease Patient Plasma Using Fiber Optical Surface Plasmon Resonance

    NASA Astrophysics Data System (ADS)

    Kim, Jisoo; Kim, SeJin; Nguyen, Tan Tai; Lee, Renee; Li, Tiehua; Yun, Changhyun; Ham, Youngeun; An, Seong Soo A.; Ju, Heongkyu

    2016-05-01

    We present a real-time quantitative immunoassay to detect fibrinogen in the blood plasma of Alzheimer's disease patients using multimode fiber optical sensors in which surface plasmon resonance (SPR) was employed. Nanometer-thick bimetals including silver and aluminum were coated onto the core surface of the clad-free part (5 cm long) of the fiber for SPR excitation at the He-Ne laser wavelength of 632.8 nm. The histidine-tagged peptide was then coated on the metal surface to immobilize the fibrinogen antibody for the selective capture of fibrinogen among the proteins in the patient blood plasma. The SPR fiber optical sensor enabled quantitative detection of concentrations of fibrinogen from the different human patient blood at a detection limit of ˜20 ng/ml. We also observed a correlation in the fibrinogen concentration measurement between enzyme-linked immunosorbent assay and our SPR fiber-based sensors. This suggests that the presented SPR fiber-based sensors that do not rely on the use of labels such as fluorophores can be used for a real-time quantitative assay of a specific protein such as fibrinogen in a human blood that is known to contain many other kinds of proteins together.

  20. Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's Disease

    PubMed Central

    Öhrfelt, Annika; Johansson, Per; Wallin, Anders; Andreasson, Ulf; Zetterberg, Henrik; Blennow, Kaj; Svensson, Johan

    2016-01-01

    Background Dysfunctions of the ubiquitin proteasome system (UPS), including the highly abundant neuronal enzyme ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and autophagy-related changes (lysosomal degradation) are implicated in several neurodegenerative disorders including Alzheimer's disease (AD). Method This study evaluated cerebrospinal fluid (CSF) levels of UCH-L1, protein deglycase (DJ-1), neuron-specific enolase (NSE), and tau phosphorylated at threonine 231 (P-tau231) in two independent patient and control cohorts. Cohort 1 included CSF samples from subjects having an AD biomarker profile (n = 10) or a control biomarker profile (n = 31), while cohort 2 was a monocenter clinical study including patients with AD (n = 32), mild cognitive impairment (n = 13), other dementias (n = 15), as well as cognitively healthy controls (n = 20). Results UCH-L1 and P-tau231 were elevated in AD patients compared to controls in both cohorts. CSF levels of DJ-1 and NSE were unchanged in the AD group, whereas they were decreased in the group of other dementia compared to controls in the clinical study. Conclusion Our main findings support that the UPS pathway may be impaired in AD, and UCH-L1 may serve as an additional CSF biomarker for AD. PMID:27504117

  1. Identification of a mutant-like conformation of p53 in fibroblasts from sporadic Alzheimer's disease patients.

    PubMed

    Uberti, Daniela; Lanni, Cristina; Carsana, Teresina; Francisconi, Simona; Missale, Cristina; Racchi, Marco; Govoni, Stefano; Memo, Maurizio

    2006-09-01

    Here we show that fibroblasts from sporadic Alzheimer's disease (AD) patients specifically express an anomalous and detectable conformational state of p53 that makes these cells distinct from fibroblasts of age-matched non-AD subjects. In particular, we found that, in contrast to non-AD fibroblasts, p53 in AD fibroblasts is expressed at higher levels in resting condition, and presents a significant impairment of its DNA binding and transcriptional activity. All together, these findings figured out the presence of a mutant-like p53 phenotype. However, gene sequencing of the entire p53 gene from either AD or non-AD did not unravel point mutations. Based on immunoprecipitation studies with conformation-specific p53 antibodies (PAb1620 and PAb240), which discriminated folded versus unfolded p53 tertiary structure, we found that a significant amount of p53 assumed an unfolded tertiary structure in fibroblasts from AD patients. This conformational mutant-like p53 form was virtually undetectable in fibroblasts from non-AD patients. These data, independently from their relevance in understanding the etiopathogenesis of AD, might be useful for supporting AD diagnosis.

  2. Altered NR4A Subfamily Gene Expression Level in Peripheral Blood of Parkinson's and Alzheimer's Disease Patients.

    PubMed

    Montarolo, Francesca; Perga, Simona; Martire, Serena; Navone, Désirée Nicole; Marchet, Alberto; Leotta, Daniela; Bertolotto, Antonio

    2016-10-01

    Parkinson's disease (PD) is a neurodegenerative pathology characterized by the degeneration of midbrain dopamine neurons, whose development and maintenance in brain is related to the transcription factor NR4A2 (also called Nurr1). Notably, NR4A2 is a neuroprotective agent with anti-inflammatory role in microglia and astrocytes. Furthermore, mutations in NR4A2 gene are associated to the familial form of PD, and its gene expression level is down-regulated in blood obtained from PD patients. NR4A2 belongs to the NR4A subfamily consisting of three members: NR4A1, NR4A2, and NR4A3. The NR4A subfamily shares high degree of homology in their molecular structure and cooperates in a spectrum of functions ranging from central nervous system to immune control during physiological and pathological conditions. Considering the close functional link between the member of NR4A subfamily, we performed a gene expression analysis of NR4A1, NR4A2, and NR4A3 in peripheral blood obtained from PD patients and healthy controls (HC). Then, in order to evaluate possible involvement of the NR4A subfamily in other neurodegenerative processes, we carried out the same analysis on blood obtained from Alzheimer's disease (AD) patients. A correlation between clinical features and gene expression was also evaluated. We found a marked down-regulated gene expression of the NR4A subfamily obtained from PD patients, but only a NR4A1 decrease in AD patients compared to HC. This study reports that the entire NR4A subfamily and not only NR4A2 could be systemically involved in PD suggesting that the study of these factors could be a promising approach to develop PD therapy.

  3. Molecular neuropathology of Alzheimer's disease.

    PubMed

    Masters, C L; Beyreuther, K

    1995-03-01

    Alzheimer's disease (AD) is caused by the aberrant metabolism of the amyloid precursor protein (APP) and is consequently associated with the accumulation of one of its degradation products, the beta A4 amyloid protein. The proteases (secretases) which generate beta A4 from APP are now being defined, as is the normal function of APP. How neurons degenerate in AD remains unexplained, but is of central importance in developing new therapeutic approaches. While the genetic factors which contribute to the aberrant metabolism of APP are now being elucidated, the environmental factors which exacerbate this process are unknown.

  4. Emerging concepts in Alzheimer's disease.

    PubMed

    Vinters, Harry V

    2015-01-01

    Alzheimer's disease/senile dementia of the Alzheimer type (AD/SDAT) is the most common neuropathologic substrate of dementia. It is characterized by synapse loss (predominantly within neocortex) as well as deposition of certain distinctive lesions (the result of protein misfolding) throughout the brain. The latter include senile plaques, composed mainly of an amyloid (Aβ) core and a neuritic component; neurofibrillary tangles, composed predominantly of hyperphosphorylated tau; and cerebral amyloid angiopathy, a microangiopathy affecting both cerebral cortical capillaries and arterioles and resulting from Aβ deposition within their walls or (in the case of capillaries) immediately adjacent brain parenchyma. In this article, I discuss the hypothesized role these lesions play in causing cerebral dysfunction, as well as CSF and neuroimaging biomarkers (for dementia) that are especially relevant as immunotherapeutic approaches are being developed to remove Aβ from the brain parenchyma. In addition, I address the role of neuropathology in characterizing the sequelae of new AD/SDAT therapies and helping to validate CSF and neuroimaging biomarkers of disease. Comorbidity of AD/SDAT and various types of cerebrovascular disease is a major theme in dementia research, especially as cognitive impairment develops in the oldest old, who are especially vulnerable to ischemic and hemorrhagic brain lesions.

  5. Treatment of Alzheimer Disease With CT Scans

    PubMed Central

    Moore, Eugene R.; Hosfeld, Victor D.; Nadolski, David L.

    2016-01-01

    Alzheimer disease (AD) primarily affects older adults. This neurodegenerative disorder is the most common cause of dementia and is a leading source of their morbidity and mortality. Patient care costs in the United States are about 200 billion dollars and will more than double by 2040. This case report describes the remarkable improvement in a patient with advanced AD in hospice who received 5 computed tomography scans of the brain, about 40 mGy each, over a period of 3 months. The mechanism appears to be radiation-induced upregulation of the patient’s adaptive protection systems against AD, which partially restored cognition, memory, speech, movement, and appetite. PMID:27103883

  6. Analysis of genetics and risk factors of Alzheimer's Disease.

    PubMed

    Panpalli Ates, M; Karaman, Y; Guntekin, S; Ergun, M A

    2016-06-14

    Alzheimer's Disease is the leading neurodegenerative cause of dementia. The pathogenesis is not clearly understood yet, is believed to be the complex interaction between genetic and environmental factors. Consequently vascular risk factors and Apolipoprotein E genotyping are increasingly gaining importance. This study aimed at assessing the relationships between Alzheimer's Disease and Apolipoprotein E phenotype and vascular risk factors. Patients diagnosed with "possible Alzheimer's Disease" in the Gazi University, Department of Neurology, were included in the study and age-matched volunteer patients who attended the polyclinic were included as a control group. In this study, the risk factors including low education level, smoking, hyperlipidemia, higher serum total cholesterol levels, and hyperhomocysteinemia were found to be statistically significantly more common in the Alzheimer's Disease group in comparison to the Control Group, while all Apolipoprotein E ε4/ε4 genotypes were found in the Alzheimer's Disease group. The presence of the Apolipoprotein E ε4 allele is believed to increase vascular risk factors as well as to affect Alzheimer's Disease directly. The biological indicators which are used in identifying the patients' genes will be probably used in the treatment plan of the patients in the future.

  7. Information and communication technology systems to improve quality of life and safety of Alzheimer's disease patients: a multicenter international survey.

    PubMed

    Pilotto, Alberto; D'Onofrio, Grazia; Benelli, Edoardo; Zanesco, Antonio; Cabello, Ana; Margelí, M Carmen; Wanche-Politis, Sophia; Seferis, Kostas; Sancarlo, Daniele; Kilias, Dimitrios

    2011-01-01

    Within the frame of the European Commission funded Smart Home for Elderly People (HOPE) Project, relatives/caregivers of 223 Alzheimer's Disease (AD) patients were recruited in Italy, Spain, and Greece for a multicenter international survey on the potential role of Information and Communication Technology system (ICT-systems) for AD patients. A five-minute video on HOPE ICT-systems was shown, and all relatives/caregivers completed a 13-item questionnaire that evaluated the potential role of: A) ICT-systems in improving quality of life, care, and safety; B) devices for monitoring personal movements, medication use, and ambient environmental conditions; C) devices to improve communication, home-based rehabilitation, and reduction of specific risks; and D) possible agreement in using ICT-systems by AD patients. Relatives/caregivers reported that ICT-systems could be very useful to improve: A) quality of life (66.4%), care (56.1%), and safety (87.0%); B) monitoring bed rest and movements (80.7%), medication use (87.4%), and ambient environmental conditions (85.2%); and C) emergency communication (83.4%). Relatives/caregivers reported that ICT-systems could be significantly more useful for AD patients aged 75-84 than patients aged <75 or ≥85 years (p < 0.0001) and with moderate than mild or severe dementia (p < 0.0001). Relatives/caregivers aged ≥50 years and with low educational level considered ICT-systems more useful than relatives/caregivers aged <50 years (p < 0.0001) and with high educational level (p < 0.0001). In conclusion, relatives/caregivers considered that the HOPE ICT-system could be useful to improve the management of AD patients.

  8. Patients with Mild Alzheimer's Disease Fail When Using Their Working Memory: Evidence from the Eye Tracking Technique.

    PubMed

    Fernández, Gerardo; Manes, Facundo; Politi, Luis E; Orozco, David; Schumacher, Marcela; Castro, Liliana; Agamennoni, Osvaldo; Rotstein, Nora P

    2016-01-01

    Patients with Alzheimer's disease (AD) develop progressive language, visuoperceptual, attentional, and oculomotor changes that can have an impact on their reading comprehension. However, few studies have examined reading behavior in AD, and none have examined the contribution of predictive cueing in reading performance. For this purpose we analyzed the eye movement behavior of 35 healthy readers (Controls) and 35 patients with probable AD during reading of regular and high-predictable sentences. The cloze predictability of words N - 1, and N + 1 exerted an influence on the reader's gaze duration. The predictabilities of preceding words in high-predictable sentences served as task-appropriate cues that were used by Control readers. In contrast, these effects were not present in AD patients. In Controls, changes in predictability significantly affected fixation duration along the sentence; noteworthy, these changes did not affect fixation durations in AD patients. Hence, only in healthy readers did predictability of upcoming words influence fixation durations via memory retrieval. Our results suggest that Controls used stored information of familiar texts for enhancing their reading performance and imply that contextual-word predictability, whose processing is proposed to require memory retrieval, only affected reading behavior in healthy subjects. In AD patients, this loss reveals impairments in brain areas such as those corresponding to working memory and memory retrieval. These findings might be relevant for expanding the options for the early detection and monitoring in the early stages of AD. Furthermore, evaluation of eye movements during reading could provide a new tool for measuring drug impact on patients' behavior.

  9. Golgi fragmentation in Alzheimer's disease

    PubMed Central

    Joshi, Gunjan; Bekier, Michael E.; Wang, Yanzhuang

    2015-01-01

    The Golgi apparatus is an essential cellular organelle for post-translational modifications, sorting, and trafficking of membrane and secretory proteins. Proper functionality of the Golgi requires the formation of its unique cisternal-stacking morphology. The Golgi structure is disrupted in a variety of neurodegenerative diseases, suggesting a common mechanism and contribution of Golgi defects in neurodegenerative disorders. A recent study on Alzheimer's disease (AD) revealed that phosphorylation of the Golgi stacking protein GRASP65 disrupts its function in Golgi structure formation, resulting in Golgi fragmentation. Inhibiting GRASP65 phosphorylation restores the Golgi morphology from Aβ-induced fragmentation and reduces Aβ production. Perturbing Golgi structure and function in neurons may directly impact trafficking, processing, and sorting of a variety of proteins essential for synaptic and dendritic integrity. Therefore, Golgi defects may ultimately promote the development of AD. In the current review, we focus on the cellular impact of impaired Golgi morphology and its potential relationship to AD disease development. PMID:26441511

  10. Predicting effective connectivity from resting-state networks in healthy elderly and patients with prodromal Alzheimer's disease.

    PubMed

    Neufang, Susanne; Akhrif, Atae; Riedl, Valentin; Förstl, Hans; Kurz, Alexander; Zimmer, Claus; Sorg, Christian; Wohlschläger, Afra M

    2014-03-01

    Using functional neuroimaging techniques two aspects of functional integration in the human brain have been investigated, functional connectivity and effective connectivity. In this study we examined both connectivity types in parallel within an executive attention network during rest and while performing an attention task. We analyzed the predictive value of resting-state functional connectivity on task-induced effective connectivity in patients with prodromal Alzheimer's disease (AD) and healthy elderly. We found that in healthy elderly, functional connectivity was a significant predictor for effective connectivity, however, it was frequency-specific. Effective top-down connectivity emerging from prefrontal areas was related with higher frequencies of functional connectivity (e.g., 0.08-0.15 Hz), in contrast to effective bottom-up connectivity going to prefrontal areas, which was related to lower frequencies of functional connectivity (e.g., 0.001-0.03 Hz). In patients, the prediction of effective connectivity by functional connectivity was disturbed. We conclude that functional connectivity and effective connectivity are interrelated in healthy brains but this relationship is aberrant in very early AD.

  11. Cognitive disability in alzheimer's disease and its management.

    PubMed

    Corsi, M; Di Raimo, T; Di Lorenzo, C; Rapp-Ricciardi, M; Archer, T; Ricci, S; Businaro, R

    2016-01-01

    Cognitive disability linked to neurodegenerative diseases and in particular to Alzheimer's disease, remains an increasing cause for concern through a dramatic prevalence increment and associated socio-economic burdens. Initially Alzheimer's disease develops asymptomatically with primary clinical signs, such as memory impairment, decline of spatial and perceptual abilities, occurring at a later stage. This delay implies the possibility of promoting early interventions during the pre-symptomatic stage of the disease. Different strategies have been applied in order to prevent/delay onset of Alzheimer's disease or at least to improve quality of life and health conditions of Alzheimer's disease patients and their caregivers, especially in the absence of current viable therapies. Multidomain interventions, aimed at affecting several risk factors simultaneously, offer a versatility that may attain improved outcomes in comparison with single-domain prevention trials. These multidomain interventions involve diet, physical exercise, cognitive training and social activities, while music therapy, improving self-consciousness and reducing neurofibrils, may contribute to deceleration/delay onset of Alzheimer's disease progression. Information and Communication Technology (ICT) provides broad applications to improve quality of life and well-being of Alzheimer's disease patients and caregivers, suffering from psychological distress, as well as reducing additional public health costs.

  12. Evidence for a membrane defect in Alzheimer disease brain

    NASA Technical Reports Server (NTRS)

    Nitsch, R. M.; Blusztajn, J. K.; Pittas, A. G.; Slack, B. E.; Growdon, J. H.; Wurtman, R. J.

    1992-01-01

    To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P less than 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P less than 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine choline-phosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease.

  13. Evidence for a membrane defect in Alzheimer disease brain.

    PubMed Central

    Nitsch, R M; Blusztajn, J K; Pittas, A G; Slack, B E; Growdon, J H; Wurtman, R J

    1992-01-01

    To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P less than 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P less than 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine choline-phosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease. PMID:1311847

  14. Confocal scanning laser tomography of the optic nerve head on the patients with Alzheimer's disease compared to glaucoma and control.

    PubMed

    Kurna, Sevda Aydin; Akar, Gokcen; Altun, Ahmet; Agirman, Yasemin; Gozke, Eren; Sengor, Tomris

    2014-12-01

    The purpose of this study was to evaluate optic nerve head (ONH) differences of the patients with Alzheimer's disease (AD) measured by confocal scanning laser tomography [Heidelberg Retina Tomograph (HRT) III] and compare with glaucoma and control subjects. Eighty-four patients were enrolled into the study: 44 eyes of 24 patients with mild to moderate AD (Group 1), 68 eyes of 35 patients with glaucoma (Group 2), and 49 eyes of 25 heathy volunteers as a control (Group 3). A complete ophthalmologic examination as well as a confocal scanning laser ophthalmoscopic assessment with HRT III were performed on all patients. Mean values of the ONH topographic parameters such as rim area (RA), rim volume (RV), height variation contour, linear cup/disc ratio, cup shape measure, and retinal nerve fiber layer (RNFL) were recorded. Mean values of RNFL thickness was 0.23 ± 0.07 in AD, 0.22 ± 0.09 in glaucoma and 0.24 ± 0.07 in the control group (p = 0.323). RA and RV were significantly lower, and linear C/D ratio was significantly higher in the glaucoma group when compared to AD and control (p < 0.05). There was no statistically significant difference between AD and control for the optic disc parameters tested (p > 0.05). We observed a negative correlation of the age with RNFL in all of the groups (p < 0.005). Age was the most important parameter affecting RNFL. Our results suggest that HRT does not demonstrate ONH differences between AD and control group, while it successfully differentiates glaucoma from AD and control cases of older age.

  15. The load of amyloid-β oligomers is decreased in the cerebrospinal fluid of Alzheimer's disease patients.

    PubMed

    Sancesario, Giulia M; Cencioni, Maria T; Esposito, Zaira; Borsellino, Giovanna; Nuccetelli, Marzia; Martorana, Alessandro; Battistini, Luca; Sorge, Roberto; Spalletta, Gianfranco; Ferrazzoli, Davide; Bernardi, Giorgio; Bernardini, Sergio; Sancesario, Giuseppe

    2012-01-01

    Amyloid-β (Aβ) oligomers are heterogeneous and instable compounds of variable molecular weight. Flow cytometry and fluorescence resonance energy transfer (FRET)-based methods allow the simultaneous detection of Aβ oligomers with low and high molecular weight in their native form. We evaluated whether an estimate of different species of Aβ oligomers in the cerebrospinal fluid (CSF) with or without dilution with RIPA buffer could be more useful in the diagnosis of Alzheimer's disease (AD) than the measurement of Aβ42 monomers, total tau (t-tau), and phosphorylated tau (p-tau). Increased t-tau (p < 0.01) and p-tau (p < 0.01), and decreased Aβ42 (p < 0.01), were detected in the CSF of patients with AD (n = 46), compared to patients with other dementia (OD) (n = 35) or with other neurological disorders (OND) (n = 56). In native CSF (n = 137), the levels of Aβ oligomers were lower (p < 0.05) in AD than in OD and OND patients; in addition, the ratio Aβ oligomers/p-tau was lower in AD than in OD (p < 0.01) and OND (p < 0.05) patients, yielding a sensitivity of 75% and a specificity of 64%. However, in CSF diluted with RIPA (n = 30), Aβ oligomers appeared higher (p < 0.05) in AD than in OND patients, suggesting they become partially disaggregated and more easily detectable after RIPA. In conclusion, FRET analysis in native CSF is essential to correctly determine the composition of Aβ oligomers. In this experimental setting, the simultaneous estimate of low and high molecular weight Aβ oligomers is as useful as the other biomarkers in the diagnosis of AD. The low amount of Aβ oligomers detected in native CSF of AD may be inversely related to their levels in the brain, as occurs for Aβ monomers, representing a biomarker for the amyloid pathogenic cascade.

  16. Cerebrospinal Aβ11-x and 17-x levels as indicators of mild cognitive impairment and patients' stratification in Alzheimer's disease

    PubMed Central

    Abraham, J-D; Promé, S; Salvetat, N; Rubrecht, L; Cobo, S; du Paty, E; Galéa, P; Mathieu-Dupas, E; Ranaldi, S; Caillava, C; Crémer, G-A; Rieunier, F; Robert, P; Molina, F; Laune, D; Checler, F; Fareh, J

    2013-01-01

    In the present work, the concentrations of Aβ11-x and Aβ17-x peptides (x=40 or 42), which result from the combined cleavages of β-amyloid precursor protein (AβPP) by β'/α or α/γ-secretases, respectively, were assessed in cerebrospinal fluid (CSF) samples from patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). Specific multiplexed assays were set up using new anti-40 and anti-42 monoclonal antibodies (mAbs) for the capture of these N-truncated Aβ peptides and anti-11 or anti-17 mAbs for their detection. The specificity, sensitivity and reproducibility of such assays were assessed using synthetic peptides and human cell models. Aβ11-x and Aβ17-x were then measured in CSF samples from patients with AD (n=23), MCI (n=23) and controls with normal cognition (n=21). Aβ11-x levels were significantly lower in patients with MCI than in controls. Compared with the combined quantification of Aβ1-42, total Tau (T-Tau) and phosphorylated Tau (P-Tau; AlzBio3, Innogenetics), the association of Aβ11-40, Aβ17-40 and T-Tau improved the discrimination between MCI and controls. Furthermore, when patients with MCI were classified into two subgroups (MCI ⩽1.5 or ⩾2 based on their CDR-SB (Cognitive Dementia Rating–Sum of Boxes) score), the CSF Aβ17-40/Aβ11-40 ratio was significantly higher in patients with CDR-SB ⩽1.5 than in controls, whereas neither Aβ1-42, T-Tau nor P-Tau allowed the detection of this subpopulation. These results need to be confirmed in a larger clinical prospective cohort. PMID:23860482

  17. Recognition of personally familiar scenes in patients with very mild Alzheimer's disease: effects of spatial frequency and luminance.

    PubMed

    Lee, Yen-Ti; Pai, Ming-Chyi

    2012-01-01

    Many community-residing patients with Alzheimer's disease (AD) have way-finding problems, particularly at twilight or on rainy days. In an attempt to understand the mechanism, we prepared pictures of street scenes, including 8 personally familiar and 8 unfamiliar, divided into Low Spatial Frequency (LSF) and Low Luminance (LL) conditions to simulate foggy or rainy days and nighttime. Each picture was presented from the most difficult (level 10) to the easiest (level 1). The participants, including 20 very mild AD patients and 20 normal controls (NC) with equal basic visual acuity, were asked to judge whether a picture was familiar or not and to describe how they came to that conclusion. The accuracy of familiar scene recognition was measured by the number of pictures successfully recognized and the ability thereof by the level needed. Compared with NC, AD patients showed poorer accuracy (2.7 ± 0.2 versus 3.6 ± 0.1, mean ± SEM, p = 0.003 under LSF; 2.8 ± 0.2 versus 3.8 ± 0.1, p = 0.001 under LL) and poorer ability (2.2 ± 0.4 versus 4.3 ± 0.4 p = 0.000 under LSF; 2.9 ± 0.3 versus 5.2 ± 0.5, p = 0.000 under LL) for both conditions. The AD patients used a global element to help judge when personally familiar scenes were displayed, which was the method NC usually adopted when presented with novel scenes. In summary, this study demonstrated poorer recognition ability in very mild AD patients when personally familiar street scenes were displayed, and the underlying mechanisms may include impaired visual search performance and efficiency. The deficits also reflect their difficulty in real life situations when their familiar environments become blurred or dark.

  18. [Cognitive decline in Alzheimer's disease. A follow three or more years of a sample of patients].

    PubMed

    Conde-Sala, Josep Lluís; Garre-Olmo, Josep; Vilalta-Franch, Joan; Llinàs-Reglà, Jordi; Turró-Garriga, Oriol; Lozano-Gallego, Manuela; Hernández-Ferràndiz, Marta; Pericot-Nierga, Imma; López-Pousa, Secundino

    2013-06-16

    Introduccion. Las tasas de declive cognitivo en los pacientes con enfermedad de Alzheimer presentan variaciones debido a diversos factores. Objetivo. Determinar la influencia de la edad, escolaridad, genero, actividades de la vida diaria (AVD) e inhibidores de la acetilcolinesterasa (IAChE) y memantina en el ritmo y tasas de declive cognitivo. Pacientes y metodos. Estudio retrospectivo de una muestra de 383 pacientes con enfermedad de Alzheimer, con evaluaciones neuropsicologicas durante un periodo superior a tres años. Se utilizo como medida cognitiva el Cambridge Cognitive Examination (CAMCOG). Se agruparon los pacientes segun su tasa de declive anual (TDA) y se realizaron analisis bivariante y de regresion lineal multivariante utilizando como variable dependiente la diferencia de puntuaciones en el CAMCOG (basal-final). Resultados. La menor edad (beta = –0,23; p < 0,001), la mayor escolaridad (beta = 0,26; p < 0,001) y el mayor deterioro de las AVD (beta = 0,24; p < 0,001) estuvieron asociados a un mayor declive en todos los pacientes. Los farmacos tuvieron un efecto benefico (beta = –0,18; p = 0,011) en el grupo con menor y mas lento declive (TDA < 5%). Conclusiones. La menor edad, la mayor escolaridad y el deterioro de las AVD se relacionan con un mayor declive cognitivo. Los IAChE y la memantina tuvieron un efecto benefico, enlenteciendo el declive en el grupo de pacientes con menor TDA.

  19. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    SciTech Connect

    Lucotte, G.; David, F.; Berriche, S.

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  20. Effects of donepezil, galantamine and rivastigmine in 938 Italian patients with Alzheimer's disease: a prospective, observational study.

    PubMed

    Santoro, Aurelia; Siviero, Paola; Minicuci, Nadia; Bellavista, Elena; Mishto, Michele; Olivieri, Fabiola; Marchegiani, Francesca; Chiamenti, Andrea Maria; Benussi, Luisa; Ghidoni, Roberta; Nacmias, Benedetta; Bagnoli, Silvia; Ginestroni, Andrea; Scarpino, Osvaldo; Feraco, Emidio; Gianni, Walter; Cruciani, Guido; Paganelli, Roberto; Di Iorio, Angelo; Scognamiglio, Mario; Grimaldi, Luigi Maria Edoardo; Gabelli, Carlo; Sorbi, Sandro; Binetti, Giuliano; Crepaldi, Gaetano; Franceschi, Claudio

    2010-02-01

    Acetylcholinesterase inhibitors (AChEIs) have been used to improve cognitive status and disability in patients with mild to moderate Alzheimer's disease (AD). However, while the efficacy of AChEIs (i.e. how they act in randomized controlled trials) in this setting is widely accepted, their effectiveness (i.e. how they behave in the real world) remains controversial. To compare the effects of three AChEIs, donepezil (Aricept), galantamine (Reminyl) and rivastigmine (Exelon), in an Italian national, prospective, observational study representative of the 'real world' clinical practice of AChEI treatment for AD. 938 patients with mild to moderate AD collected within the framework of the Italian National Cronos Project (CP), involving several UVAs (AD Evaluation Units) spread over the entire national territory, who were receiving donepezil, galantamine or rivastigmine were followed for 36 weeks by measuring: (i) function, as determined by the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales; (ii) cognition, as measured by the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) [primary outcome measures]; and (iii) behaviour, as measured on the Neuropsychiatric Inventory (NPI) and Clinical Dementia Rating (CDR) scale. Moreover, all patients were genotyped for apolipoprotein E (apoE) genetic variants. No statistically significant improvement in the primary outcome measures (MMSE and ADAS-Cog) was observed with drug therapy at 36 weeks, at which point all groups had lost, on average, 1 point on the MMSE and gained 2-3 points on the ADAS-Cog scale compared with baseline. On the secondary outcome measures at week 36, all treatment groups showed a significant worsening on the ADL and IADL scales compared with baseline, while on the NPI scale there were no significant differences from baseline except for the galantamine-treated group which worsened significantly. Moreover

  1. Emerging therapeutics for Alzheimer's disease.

    PubMed

    Chiang, Karen; Koo, Edward H

    2014-01-01

    Despite decades of intense research, therapeutics for Alzheimer's disease (AD) are still limited to symptomatic treatments that possess only short-term efficacy. Recently, several large-scale Phase III trials targeting amyloid-β production or clearance have failed to show efficacy, leading to a reexamination of the amyloid hypothesis as well as highlighting the need to explore alternatives in both clinical testing strategies and drug discovery targets. In this review, we discuss therapeutics currently being tested in clinical trials and up-and-coming interventions that have shown promise in animal models, devoting attention to the mechanisms that may underlie their ability to influence disease progression and placing particular emphasis on tau therapeutics.

  2. Facilitating Alzheimer disease research recruitment.

    PubMed

    Grill, Joshua D; Galvin, James E

    2014-01-01

    Alzheimer disease (AD) research faces challenges to successful enrollment, especially to clinical trials and biomarker studies. Failure to recruit the planned number of participants in a timely manner threatens the internal validity and success of clinical research, raising concerns about external validity and generalizability of results, and possibly leading to disparities in disease treatment. Methods to improve recruitment exist, but require varying levels of staff effort and financial resources, and evidence of effectiveness is often lacking or inconsistent. In this review, we summarize some of the available methods to improve AD research recruitment, the available literature to support or refute these strategies, and some of the experiences at the authors' AD Research Centers. We discuss the use of community-based participatory research principles and participant registries as a means to enhance research enrollment and increase diversity of research samples.

  3. [Gene therapy and Alzheimer's disease].

    PubMed

    Li, Jian; Li, Wenwen; Zhou, Jun

    2015-04-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the presence of extracellular β-amyloid in the senile plaques, intracellular aggregates of abnormal phosphorylation of tau protein in the neurofibrillary tangles, neuronal loss and cerebrovascular amyloidosis. The manifestations of clinical symptoms include memory impairment, cognitive decline, altered behavior and language deficit. Currently available drugs in AD therapy consist of acetylcholinesterase inhibitors, NMDA receptor antagonists, non-steroidal anti-inflammatory drugs, etc. These drugs can only alleviate the symptoms of AD. Gene therapy is achieved by vector-mediated gene transfer technology, which can delivery DNA or RNA into target cells to promote the expression of a protective or therapeutic protein and silence certain virulence genes.

  4. Pattern of extrapyramidal signs in Alzheimer's disease.

    PubMed

    Tosto, Giuseppe; Monsell, Sarah E; Hawes, Stephen E; Mayeux, Richard

    2015-11-01

    Patients with Alzheimer's disease (AD) often develop extrapyramidal signs (EPS), which increase in frequency as the disease progresses. We aimed to investigate the patterns of presentation of EPS in AD and their correlation with clinical and neuropathological features. 4284 subjects diagnosed with AD from the National Alzheimer's Coordinating Center (NACC) database with at least one abnormal Unified Parkinson's Disease Rating Scale (UPDRS) assessment were included. Individuals were assigned to a discovery sample and a sensitivity analysis sample (moderate and mild dementia, respectively) and a subset of subjects provided neuropathological data (n = 284). Individuals from the Washington Heights and Inwood Columbia Aging Project (WHICAP) served as validation sample. Patterns of presentation of EPS were identified employing categorical principal component analysis (CATPCA). Six principal components were identified in both mild and moderate AD samples: (I) hand movements, alternating movements, finger tapping, leg agility ("limbs bradykinesia"); (II) posture, postural instability, arising from chair, gait and body bradykinesia/hypokinesia ("axial"); (III) limb rigidity ("rigidity"); (IV) postural tremor; (V) resting tremor; (VI) speech and facial expression. Similar results were obtained in the WHICAP cohort. Individuals with hallucinations, apathy, aberrant night behaviors and more severe dementia showed higher axial and limb bradykinesia scores. "Limb bradykinesia" component was associated with a neuropathological diagnosis of Lewy body disease and "axial" component with reduced AD-type pathology. Patterns of EPS in AD show distinct clinical and neuropathological correlates; they share a pattern of presentation similar to that seen in Parkinson's disease, suggesting common pathogenic mechanisms across neurodegenerative diseases.

  5. The Modified Frontal Behavioral Inventory (FBI-mod) for Patients with Frontotemporal Lobar Degeneration, Alzheimer's Disease, and Mild Cognitive Impairment.

    PubMed

    Suhonen, Noora-Maria; Hallikainen, Ilona; Hänninen, Tuomo; Jokelainen, Jari; Krüger, Johanna; Hall, Anette; Pikkarainen, Maria; Soininen, Hilkka; Remes, Anne M

    2017-01-01

    While behavioral symptoms are both early and prevalent features of behavioral variant frontotemporal dementia (bvFTD), they can be present in other types of dementia as well, including Alzheimer's disease (AD) and even mild cognitive impairment (MCI). The Frontal Behavioral Inventory (FBI) was specifically developed to capture the behavioral and personality changes in bvFTD; it has also been modified into a self-administered caregiver questionnaire (FBI-mod). We examined the utility of the FBI-mod in differentiating bvFTD (n = 26), primary progressive aphasia (PPA) (n = 7), AD (n = 53), and MCI (n = 50) patients, and investigated how the FBI-mod may be associated with neuropsychological measures. The bvFTD patients scored significantly higher as compared to all other patient groups on the FBI-mod Total (p < 0.005), Negative (p < 0.005), and Positive (p < 0.01) scores. The cut-off point for the FBI-mod Total score that best discriminated the bvFTD and AD patients in our sample was 16, thus substantially lower than reported for the original FBI. For the bvFTD group, only mild correlations emerged between the FBI-mod and the cognitive measures. However, significant correlations between the FBI-mod and depressive symptoms as measured by the BDI-II were found for bvFTD. This suggests that while behavioral symptoms appear independent from cognitive deficits in bvFTD, they may nevertheless be interrelated with depressive symptoms. We conclude that the FBI-mod is an easily administered behavioral scale that can aid in differential diagnosis of bvFTD and should be used in clinical practice. The FBI-mod may further be considered as an outcome measure in clinical trials.

  6. Behavioral and Electrophysiological Correlates of Memory Binding Deficits in Patients at Different Risk Levels for Alzheimer's Disease.

    PubMed

    Pietto, Marcos; Parra, Mario A; Trujillo, Natalia; Flores, Facundo; García, Adolfo M; Bustin, Julian; Richly, Pablo; Manes, Facundo; Lopera, Francisco; Ibáñez, Agustín; Baez, Sandra

    2016-06-30

    Deficits in visual short-term memory (VSTM) binding have been proposed as an early and specific marker for Alzheimer's disease (AD). However, no studies have explored the neural correlates of this domain in clinical categories involving prodromal stages with different risk levels of conversion to AD. We assessed underlying electrophysiological modulations in patients with mild cognitive impairment (MCI), patients in the MCI stages of familial AD carrying the mutation E280A of the presenilin-1 gene (MCI-FAD), and healthy controls. Moreover, we compared the behavioral performance and neural correlates of both patient groups. Participants completed a change-detection VSTM task assessing recognition of changes between shapes or shape-color bindings, presented in two consecutive arrays (i.e., study and test) while event related potentials (ERPs) were recorded. Changes always occurred in the test array and consisted of new features replacing studied features (shape-only) or features swapping across items (shape-color binding). Both MCI and MCI-FAD patients performed worse than controls in the shape-color binding condition. Early electrophysiological activity (100-250 ms) was significantly reduced in both clinical groups, particularly over fronto-central and parieto-occipital regions. However, shape-color binding performance and their reduced neural correlates were similar between MCI and MCI-FAD. Our results support the validity of the VSTM binding test and their neural correlates in the early detection of AD and highlight the importance of studies comparing samples at different risk for AD conversion. The combined analysis of behavioral and ERP data gleaned with the VSTM binding task can offer a valuable memory biomarker for AD.

  7. [Mental time dysfunction in Parkinson's and Alzheimer's diseases].

    PubMed

    Honma, Motoyasu; Kuroda, Takeshi; Futamura, Akinori; Sugimoto, Azusa; Kawamura, Mitsuru

    2015-03-01

    Mental time is altered by a number of factors and the underlying neural processing involved is highly complicated. Recent research suggests that mental time in patients with particular neurological diseases is perceptually shorter than in normal individuals. This review introduces mental time dysfunction and a model for processing of mental time in Parkinson's and Alzheimer's disease. Although the two diseases show the same dysfunction of mental time in behavior, we expect the underlying neural mechanism to vary in each disease. It is possible that the dysfunction of mental time in Parkinson's disease is caused by the abnormal striatum acting as a pacemaker, while that in Alzheimer's disease is caused by abnormal hippocampal memory.

  8. Efficacy and safety of galantamine treatment for patients with Alzheimer's disease: a meta-analysis of randomized controlled trials.

    PubMed

    Jiang, Deqi; Yang, Xiujuan; Li, Mingxing; Wang, Yan; Wang, Yong

    2015-08-01

    Cholinesterase inhibitors treatment is considered as a common therapeutic approach for Alzheimer's disease (AD) by numerous reported studies, but the role of currently available drugs for AD is still controversial. Our study aimed to evaluate the efficacy and safety of galantamine for the treatment of AD, and provide the basis and reference for clinical rational drug use. Randomized controlled trials (RCTs) of galantamine for AD published up to April 30, 2014 were searched. A random or fixed-effect model was used to analyze outcomes which were expressed as risk ratios (RRs) or mean difference (MD) with a 95 % confidence interval (CI). Heterogeneity was assessed by Q test and I(2) statistic. The outcome measurements were as follows: the changes of Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL), Neuropsychiatric Inventory (NPI), Clinicians' Interview-Based Impression of Change with Caregiver's Input (CIBIC+), adverse effects and dropouts. Eleven articles with 4,074 participants were included. Administration of galantamine for 8-28 weeks (16-40 mg daily) led to significant improvements in ADAS-cog score [P < 0.00001, MD = -2.95, 95 % CI (-3.32, -2.57)], MMSE score [P = 0.003, MD = 2.50, 95 % CI (0.86, 4.15)], NPI score [P = 0.001, MD = -1.58, 95 % CI (-2.54, -0.62)], and CIBIC+ scale [P < 0.00001, RR = 1.26, 95 % CI (1.15, 1.39)], but not in ADL score [P = 0.43, MD = 0.71, 95 % CI (-1.07, 2.48)]. More adverse events and dropouts occurred in the galantamine group than that in the placebo group, the differences were statistically significant (all P < 0.05). Galantamine could significantly improve cognitive, behavioral, and global performances in patients with AD. In addition, we need to use it with caution in the clinical treatment.

  9. What Are the Signs of Alzheimer's Disease?

    MedlinePlus

    ... Contents It's important to know the signs of Alzheimer's disease. If you know the signs, you can get help right away. Some signs of the disease are listed here: Diagnosis Doctors now have several methods and tools to ...

  10. Support for an hypothesis linking Alzheimer`s disease and Down syndrome

    SciTech Connect

    Geller, L.N.; Benjamin, M.B.; Dressler, D.

    1994-09-01

    A connection between Alzheimer`s disease (AD) and Down syndrome (trisomy 21) is indicated by the fact that Down syndrome individuals develop AD neuropathology by the third or fourth decade of life. One explanation for the connection between AD and Down syndrome would be that the overexpression of a gene or genes on chromosome 21 results in Alzheimer`s disease, the most likely candidate being the amyloid precursor protein (APP) gene. However, mutations in the APP gene have been found to be associated with only a very small percentage of familial AD cases. An alternative cause of some Alzheimer`s disease cases may be sporadic trisomy of chromosome 21, resulting from mutations or toxins that cause chromosome nondisjunction. Several predictions can be made based on this hypothesis. One prediction is that there should be more trisomy 21 in cells from AD individuals than from unaffected controls. Using quantitative fluorescence in situ hybridization to compare the number of trisomy chromosome 21 cells in cultured fibroblasts from AD and unaffected individuals, we have shown that there are a significantly larger number of trisomy 21 cells from AD individuals. Another prediction is that a defect in the mitotic spindle apparatus could be the underlying cause of the aneuploidy. Cultured lymphoblasts from AD and unaffected individuals were briefly exposed to the microtubule-disrupting agent colchicine. As assayed by the subsequent appearance of metaphase chromosomes showing centromere separation, cells from AD patients were significantly more sensitive to colchicine treatment compared to cells from unaffected individuals, supporting the prediction of an altered spindle apparatus. Finally, we would predict that both types of patients should share some physical symptoms. We have also found that AD, like Down`s patients, are hypersensitive to the effect of the cholinergic antagonist, tropicamide, on pupil dilation, which may serve as a diagnostic test for Alzheimer`s disease.

  11. Patients that have Undergone Hemodialysis Exhibit Lower Amyloid Deposition in the Brain: Evidence Supporting a Therapeutic Strategy for Alzheimer's Disease by Removal of Blood Amyloid.

    PubMed

    Sakai, Kazuyoshi; Senda, Takao; Hata, Ryuji; Kuroda, Makoto; Hasegawa, Midori; Kato, Masao; Abe, Masato; Kawaguchi, Kazunori; Nakai, Shigeru; Hiki, Yoshiyuki; Yuzawa, Yukio; Kitaguchi, Nobuya

    2016-01-01

    As a proof of concept that removal of blood amyloid-β (Aβ) can reduce Aβ deposition in the brains of patients with Alzheimer's disease, cortices of patients who had undergone hemodialysis (HD), which removes Aβ from the blood, were histochemically analyzed; postmortem brain sections were stained with anti-Aβ antibodies. Brains from patients who had undergone HD had significantly fewer senile plaques than those of patient who had not undergone HD. This significant difference was also confirmed by silver staining. Our findings suggest that removal of blood Aβ by hemodialysis results in lower accumulation of Aβ in the brain.

  12. Estrogen-Related Factors in the Frontal Lobe of Alzheimer's Disease Patients and Importance of Body Mass Index.

    PubMed

    Honma, Naoko; Saji, Shigehira; Mikami, Tetuo; Yoshimura, Noriko; Mori, Seijiro; Saito, Yuko; Murayama, Shigeo; Harada, Nobuhiro

    2017-04-07

    Estrogens play a physiologically important role in the brain, but controversies exist regarding the association between Alzheimer's disease (AD) and estrogens. Estrogen-related factors were comprehensively examined in frontal lobe tissues from autopsied AD patients, and compared with controls. Concentrations of estrogens, expression of estrogen receptors (ERs), and estrogen-metabolizing enzymes (EMEs) which are important for determining the peripheral estrogen concentrations, were examined using liquid chromatography tandem mass spectrometry, immunohistochemistry, and quantitative real-time PCR, respectively. Body mass index (BMI), known to correlate with the serum estrogen concentrations, was also taken into consideration. There were no significant differences in estrogen concentrations or each EME level between the two groups in both the cortex and white matter, whereas glial nuclear ER-β expression was significantly lower in white matter from the AD group than the control group (Allred score, 3.2 ± 0.3 and 6.5 ± 0.3, respectively. P < 0.0001). Estrogen concentrations were found to closely correlate with BMI, particularly in controls. ER-β loss in the white matter from the AD group suggests the necessity of studying the effects of estrogens on glias as well as neurons in the etiology of AD. The correlation between BMI and estrogen concentrations in the frontal lobe suggests the importance of non-brain sources of estrogens.

  13. Abnormal tau phosphorylation in the thorny excrescences of CA3 hippocampal neurons in patients with Alzheimer's disease.

    PubMed

    Blazquez-Llorca, Lidia; Garcia-Marin, Virginia; Merino-Serrais, Paula; Ávila, Jesús; DeFelipe, Javier

    2011-01-01

    A key symptom in the early stages of Alzheimer's disease (AD) is the loss of declarative memory. The anatomical substrate that supports this kind of memory involves the neural circuits of the medial temporal lobe, and in particular, of the hippocampal formation and adjacent cortex. A main feature of AD is the abnormal phosphorylation of the tau protein and the presence of tangles. The sequence of cellular changes related to tau phosphorylation and tangle formation has been studied with an antibody that binds to diffuse phosphotau (AT8). Moreover, another tau antibody (PHF-1) has been used to follow the pathway of neurofibrillary (tau aggregation) degeneration in AD. We have used a variety of quantitative immunocytochemical techniques and confocal microscopy to visualize and characterize neurons labeled with AT8 and PHF-1 antibodies. We present here the rather unexpected discovery that in AD, there is conspicuous abnormal phosphorylation of the tau protein in a selective subset of dendritic spines. We identified these spines as the typical thorny excrescences of hippocampal CA3 neurons in a pre-tangle state. Since thorny excrescences represent a major synaptic target of granule cell axons (mossy fibers), such aberrant phosphorylation may play an essential role in the memory impairment typical of AD patients.

  14. Comparison of histological techniques to visualize iron in paraffin-embedded brain tissue of patients with Alzheimer's disease.

    PubMed

    van Duijn, Sara; Nabuurs, Rob J A; van Duinen, Sjoerd G; Natté, Remco

    2013-11-01

    Better knowledge of the distribution of iron in the brains of Alzheimer's disease (AD) patients may facilitate the development of an in vivo magnetic resonance (MR) marker for AD and may cast light on the role of this potentially toxic molecule in the pathogenesis of AD. Several histological iron staining techniques have been used in the past but they have not been systematically tested for sensitivity and specificity. This article compares three histochemical techniques and ferritin immunohistochemistry to visualize iron in paraffin-embedded human AD brain tissue. The specificity of the histochemical techniques was tested by staining sections after iron extraction. Iron was demonstrated in the white matter, in layers IV/V of the frontal neocortex, in iron containing plaques, and in microglia. In our hands, these structures were best visualized using the Meguro iron stain, a method that has not been described for iron staining in human brain or AD in particular. Ferritin immunohistochemistry stained microglia and iron containing plaques similar to the Meguro method but was less intense in myelin-associated iron. The Meguro method is most suitable for identifying iron-positive structures in paraffin-embedded human AD brain tissue.

  15. Alzheimer's disease: insights from epidemiology.

    PubMed

    McDowell, I

    2001-06-01

    While a complete understanding of the pathogenesis of Alzheimer's disease (AD) remains elusive, many conclusions can be drawn from the numerous epidemiological studies undertaken to date. Prevalence and incidence estimates show consistency, following a roughly exponential pattern with a doubling of both parameters roughly every five years after age 65. Roughly 7% of the population aged 65 and over has AD. The clinical course of the disease is reasonably well established and mortality rates rise with increasing levels of cognitive deficit. Four risk factors for AD are firmly established: increasing age, the presence of the apolipoproteinE-epsilon4 allele, familial aggregation of cases, and Down's syndrome. Numerous other associations have been shown in some studies, but not in others. For example, women generally appear at higher risk than men, as do people with lower levels of education; depression is probably prodromal; head injury is an established risk factor, and may interact with the apoE gene; several occupational exposures appear hazardous, and exposure to aluminum in the water supply confers excess risk. Hypertension and other vascular symptoms appear to predispose to AD, which is now seen as nosologically closer to vascular dementia than was previously believed. Several apparently protective factors have been identified, although preventive trials based on these have so far shown minimal effectiveness. The use of non-steroidal anti-inflammatory drugs to treat arthritis is associated with a reduced risk of AD, as is estrogen use by post-menopausal women. Physical activity appears beneficial, as does a diet with high levels of vitamins B6, B12 and folate. while red wine in moderate quantities appears protective. This review concludes with a discussion of the strengths and limitations of current epidemiological methods for studying Alzheimer's disease.

  16. Current and future treatments for Alzheimer's disease.

    PubMed

    Salloway, Stephen

    2009-08-01

    There are currently >5 million people in the United States who have been diagnosed with Alzheimer's disease. That prevalence rate is expected to triple as the population ages. The health and economic burden due to Alzheimer's disease is a worldwide problem, with some of the greatest burden coming from the developing world as people live longer in those societies. Throughout the world, the projected growth of Alzheimer's disease is dramatic. This is a worldwide public health problem of the highest order, and there is a compelling need to develop new treatments and methods of earlier diagnosis need to slow the progression of the disease and lessen its impact.

  17. Alzheimer's disease camouflaged by histrionic personality disorder.

    PubMed

    Hellwig, Sabine; Dykierek, Petra; Hellwig, Bernhard; Zwernemann, Stefan; Meyer, Philipp T

    2012-02-01

    A common condition in Alzheimer's disease (AD) is unawareness of deficits. Different concepts try to elucidate the nature of this symptom. An essential question relates to the interaction of organic and psychogenic factors. Here we present a patient who displayed her cognitive deficits as attention-seeking behaviour. There was a history of histrionic personality disorder according to ICD-10 criteria. Unexpectedly, the final diagnosis after extensive diagnostic work-up was AD. The unusual coincidence of AD and a histrionic personality disorder hampered the clinical process of diagnosing dementia. We discuss unawareness as a complex concept incorporating neuroanatomical, psychiatric, and psychosocial aspects.

  18. A positron emission tomography microdosing study with a potential antiamyloid drug in healthy volunteers and patients with Alzheimer's disease.

    PubMed

    Bauer, Martin; Langer, Oliver; Dal-Bianco, Peter; Karch, Rudolf; Brunner, Martin; Abrahim, Aiman; Lanzenberger, Rupert; Hofmann, Andrea; Joukhadar, Christian; Carminati, Paolo; Ghirardi, Orlando; Piovesan, Paola; Forloni, Gianluigi; Corrado, Mario E; Lods, Nadège; Dudczak, Robert; Auff, Eduard; Kletter, Kurt; Müller, Markus

    2006-09-01

    This work describes a microdosing study with an investigational, carbon 11-labeled antiamyloid drug, 1,1'-methylene-di-(2-naphthol) (ST1859), and positron emission tomography (PET) in healthy volunteers (n = 3) and patients with Alzheimer's disease (n = 6). The study aimed to assess the distribution and local tissue pharmacokinetics of the study drug in its target organ, the human brain. Before PET studies were performed in humans, the toxicologic characteristics of ST1859 were investigated by an extended single-dose toxicity study according to guidelines of the Food and Drug Administration and European Medicines Agency, which are relevant for clinical trials with a single microdose. After intravenous bolus injection of 341 +/- 21 MBq [(11)C]ST1859 (containing <11.4 nmol of unlabeled ST1859), peripheral metabolism was rapid, with less than 20% of total plasma radioactivity being in the form of unchanged parent drug at 10 minutes after administration. In both the control and patient groups, uptake of radioactivity into the brain was relatively fast (time to reach maximum concentration, 9-17 minutes) and pronounced (maximum concentration [standardized uptake value], 1.3-2.2). In both healthy volunteers and patients, there was a rather uniform distribution of radioactivity in the brain, including both amyloid-beta-rich and -poor regions, with slow washout of radioactivity (half-life, 82-185 minutes). In conclusion, these data provide important information on the blood-brain barrier penetration and metabolism of an investigational antiamyloid drug and suggest that the PET microdosing approach is a useful method to describe the target-organ pharmacokinetics of radiolabeled drugs in humans.

  19. Classification of Alzheimer's disease patients with hippocampal shape wrapper-based feature selection and support vector machine

    NASA Astrophysics Data System (ADS)

    Young, Jonathan; Ridgway, Gerard; Leung, Kelvin; Ourselin, Sebastien

    2012-02-01

    It is well known that hippocampal atrophy is a marker of the onset of Alzheimer's disease (AD) and as a result hippocampal volumetry has been used in a number of studies to provide early diagnosis of AD and predict conversion of mild cognitive impairment patients to AD. However, rates of atrophy are not uniform across the hippocampus making shape analysis a potentially more accurate biomarker. This study studies the hippocampi from 226 healthy controls, 148 AD patients and 330 MCI patients obtained from T1 weighted structural MRI images from the ADNI database. The hippocampi are anatomically segmented using the MAPS multi-atlas segmentation method, and the resulting binary images are then processed with SPHARM software to decompose their shapes as a weighted sum of spherical harmonic basis functions. The resulting parameterizations are then used as feature vectors in Support Vector Machine (SVM) classification. A wrapper based feature selection method was used as this considers the utility of features in discriminating classes in combination, fully exploiting the multivariate nature of the data and optimizing the selected set of features for the type of classifier that is used. The leave-one-out cross validated accuracy obtained on training data is 88.6% for classifying AD vs controls and 74% for classifying MCI-converters vs MCI-stable with very compact feature sets, showing that this is a highly promising method. There is currently a considerable fall in accuracy on unseen data indicating that the feature selection is sensitive to the data used, however feature ensemble methods may overcome this.

  20. When is category specific in Alzheimer's disease?

    PubMed

    Laws, Keith R; Gale, Tim M; Leeson, Verity C; Crawford, John R

    2005-08-01

    Mixed findings have emerged concerning whether category-specific disorders occur in Alzheimer's disease. Factors that may contribute to these inconsistencies include: ceiling effects/skewed distributions for control data in some studies; differences in the severity of cognitive deficit in patients; and differences in the type of analysis (in particular, if and how controls are used to analyse single case data). We examined picture naming in Alzheimer's patients and matched elderly healthy normal controls in three experiments. These experiments used stimuli that did and did not produce ceiling effects/skewed data in controls. In Experiment 1, we examined for category effects in individual DAT patients using commonly used analyses for single cases (chi2 and z-scores). The different techniques produced quite different outcomes. In Experiment 2a, we used the same techniques on a different group of patients with similar outcomes. Finally, in Experiment 2b, we examined the same patients but (a) used stimuli that did not produce ceiling effects/skewed distributions in healthy controls, and (b) used statistical methods that did not treat the control sample as a population. We found that ceiling effects in controls may markedly inflate the incidence of dissociations in which living things are differentially impaired and seriously underestimate dissociations in the opposite direction. In addition, methods that treat the control sample as a population led to inflation in the overall number of dissociations detected. These findings have implications for the reliability of category effects previously reported both in Alzheimer patients and in other pathologies. In particular, they suggest that the greater proportion of living than nonliving deficits reported in the literature may be an artifact of the methods used.

  1. Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients

    PubMed Central

    Corrêa, Márcio Silveira; Giacobbo, Bruno Lima; Vedovelli, Kelem; de Lima, Daiane Borba; Ferrari, Pamela; Argimon, Irani Iracema de Lima; Walz, Julio Cesar

    2016-01-01

    Objectives Older familial caregivers of Alzheimer’s disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers. Method The cognitive measures of 17 young (31–58 years) and 18 old (63–84 years) caregivers and of 17 young (37–57 years) and 18 old (62–84 years) non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA) levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in serum. Results Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups. Discussion Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions. PMID:27706235

  2. How does diabetes accelerate Alzheimer disease pathology?

    PubMed

    Sims-Robinson, Catrina; Kim, Bhumsoo; Rosko, Andrew; Feldman, Eva L

    2010-10-01

    Diabetes and Alzheimer disease (AD)-two age-related diseases-are both increasing in prevalence, and numerous studies have demonstrated that patients with diabetes have an increased risk of developing AD compared with healthy individuals. The underlying biological mechanisms that link the development of diabetes with AD are not fully understood. Abnormal protein processing, abnormalities in insulin signaling, dysregulated glucose metabolism, oxidative stress, the formation of advanced glycation end products, and the activation of inflammatory pathways are features common to both diseases. Hypercholesterolemia is another factor that has received attention, owing to its potential association with diabetes and AD. This Review summarizes the mechanistic pathways that might link diabetes and AD. An understanding of this complex interaction is necessary for the development of novel drug therapies and lifestyle guidelines aimed at the treatment and/or prevention of these diseases.

  3. Immunotherapeutic approaches for Alzheimer's disease.

    PubMed

    Wisniewski, Thomas; Goñi, Fernando

    2015-03-18

    Alzheimer's disease (AD) is the most prevalent form of dementia worldwide and is an emerging global epidemic. It is characterized by an imbalance between production and clearance of amyloid β (Aβ) and tau proteins. Oligomeric forms of Aβ and tau are believed to be the most toxic. Dramatic results from AD animal models showed great promise for active and passive immune therapies targeting Aβ. However, there is very limited evidence in human studies of the clinical benefits from these approaches. Immunotherapies targeting only tau pathology have had some success but are limited so far to mouse models. The majority of current methods is based on immunological targeting of a self-protein; hence, benefits need to be balanced against risks of stimulating excessive autoimmune toxic inflammation. For greater efficacy the next generation of vaccines needs to focus more on concurrently targeting all the intermediate toxic conformers of oligomeric Aβ and tau species.

  4. Alzheimer's disease and gut microbiota.

    PubMed

    Hu, Xu; Wang, Tao; Jin, Feng

    2016-10-01

    Alzheimer's disease (AD) is a most common neurodegenerative disorder, which associates with impaired cognition. Gut microbiota can modulate host brain function and behavior via microbiota-gut-brain axis, including cognitive behavior. Germ-free animals, antibiotics, probiotics intervention and diet can induce alterations of gut microbiota and gut physiology and also host cognitive behavior, increasing or decreasing risks of AD. The increased permeability of intestine and blood-brain barrier induced by gut microbiota disturbance will increase the incidence of neurodegeneration disorders. Gut microbial metabolites and their effects on host neurochemical changes may increase or decrease the risk of AD. Pathogenic microbes infection will also increase the risk of AD, and meanwhile, the onset of AD support the "hygiene hypothesis". All the results suggest that AD may begin in the gut, and is closely related to the imbalance of gut microbiota. Modulation of gut microbiota through personalized diet or beneficial microbiota intervention will probably become a new treatment for AD.

  5. [How to handle the dilemma of driving for patients with Alzheimer's disease? A survey of advices provided by French caregivers guides].

    PubMed

    Mietkiewicz, Marie-Claude; Ostrowski, Madeleine

    2015-09-01

    For many old people, driving takes an important place in the daily living activities and contributes to carry on their autonomy and self-esteem. However, many studies showed a link between car accidents and Alzheimer's disease, even in the early stages of dementia, and people caring for these patients inevitably ask the question: "Is my patient with Alzheimer's disease still able to drive his car?" Guides devoted to caregivers can play an important role to improve the knowledge of Alzheimer's disease and to afford advices for patients managing. To assess how these guides handle the question of patients driving, we made a survey of the 46 French caregiver guides (re)published between 1988 and 2013. The question of driving is raised with more or less details in 31 guides. All state that driving should be discontinued but that the consequences of this decision on the patient autonomy should be taken into account. A few guides provide clues to assess driving competence for the patients, and many propose advices to support the implementation of the driving discontinuity decision, such as to discuss with the patient to persuade him to stop driving, to ask for assistance by the family physician, to hide the car's keys or to disconnect its battery... In France, physicians are not allowed to prohibit driving or to report dangerous driving to authorities. Ultimately, the caregivers remain faced with the ethical dilemma to choose between safety and the patient's autonomy preservation. Therefore the responsibility for the patient to persist or give up driving only falls to them.

  6. Quantitative sensory testing and pain tolerance in patients with mild to moderate Alzheimer disease compared to healthy control subjects.

    PubMed

    Jensen-Dahm, Christina; Werner, Mads U; Dahl, Jørgen B; Jensen, Troels Staehelin; Ballegaard, Martin; Hejl, Anne-Mette; Waldemar, Gunhild

    2014-08-01

    Patients with Alzheimer disease (AD) report pain less frequently than their cognitively intact peers. It has been hypothesized that pain processing is altered in AD. The aim of this study was to investigate agreement and reliability of 3 pain sensitivity tests and to examine pain threshold and tolerance in patients with AD. We examined 29 patients with mild to moderate AD and 29 age- and gender-matched healthy control subjects with quantitative sensory testing, ie, assessments of detection threshold (warmth detection threshold [WDT]) and pain threshold (heat pain threshold [HPT], pressure algometry, cold pressor test), and assessments of tolerance (pressure algometry, cold pressor test). All procedures were done twice on day 1, 1 hour apart, and repeated on day 2. We found no difference between groups for WDT (patient vs control subjects: mean [95% confidence interval]: 35.5°C [33.4°C to 37.6°C] vs 35.4°C [34.3°C to 36.5°C], P=.8) or HPT (41.2°C [40.0°C to 42.4°C] vs 42.3°C [41.1°C to 43.5°C], P=.24). We observed comparable thresholds for pressure algometry (median [25% to 75% interquartile range]: 120 kPa [100 to 142 kPa] vs 131 kPa [113 to 192 kPa], P=.10), but significantly lower tolerance in AD patients (213 kPa [188 to 306 kPa] vs 289 kPa [262 to 360 kPa], P=.008). No differences were found for the cold pressor test. The study demonstrated good replicability of the sensory testing data with comparable data variability, for both groups, which supports the use of these methods in studies of patients with mild to moderate AD. Contrary to previous studies, we observed a reduced pain tolerance in patients with mild to moderate AD, which suggests that the reduced report of pain cannot be explained by reduced processing of painful stimuli.

  7. [Non-verbal communication in Alzheimer's disease].

    PubMed

    Schiaratura, Loris Tamara

    2008-09-01

    This review underlines the importance of non-verbal communication in Alzheimer's disease. A social psychological perspective of communication is privileged. Non-verbal behaviors such as looks, head nods, hand gestures, body posture or facial expression provide a lot of information about interpersonal attitudes, behavioral intentions, and emotional experiences. Therefore they play an important role in the regulation of interaction between individuals. Non-verbal communication is effective in Alzheimer's disease even in the late stages. Patients still produce non-verbal signals and are responsive to others. Nevertheless, few studies have been devoted to the social factors influencing the non-verbal exchange. Misidentification and misinterpretation of behaviors may have negative consequences for the patients. Thus, improving the comprehension of and the response to non-verbal behavior would increase first the quality of the interaction, then the physical and psychological well-being of patients and that of caregivers. The role of non-verbal behavior in social interactions should be approached from an integrative and functional point of view.

  8. Competitive segmentation of the hippocampus and the amygdala from MRI data: validation on young healthy controls and Alzheimer's disease patients

    NASA Astrophysics Data System (ADS)

    Chupin, Marie; Hasboun, Dominique; Mukuna-Bantumbakulu, Romain; Bardinet, Eric; Baillet, Sylvain; Kinkingnéhun, Serge; Lemieux, Louis; Dubois, Bruno; Garnero, Line

    2006-03-01

    The hippocampus (Hc) and the amygdala (Am) are two cerebral structures that play a central role in main cognitive processes. Their segmentation allows atrophy in specific neurological illnesses to be quantified, but is made difficult by the complexity of the structures. In this work, a new algorithm for the simultaneous segmentation of Hc and Am based on competitive homotopic region deformations is presented. The deformations are constrained by relational priors derived from anatomical knowledge, namely probabilities for each structure around automatically retrieved landmarks at the border of the objects. The approach is designed to perform well on data from diseased subjects. The segmentation is initialized by extracting a bounding box and positioning two seeds; total execution time for both sides is between 10 and 15 minutes including initialization for the two structures. We present the results of validation based on comparison with manual segmentation, using volume error, spatial overlap and border distance measures. For 8 young healthy subjects the mean volume error was 7% for Hc and 11% for Am, the overlap: 84% for Hc and 83% for Am, the maximal distance: 4.2mm for Hc and 3.1mm for Am; for 4 Alzheimer's disease patients the mean volume error was 9% for Hc and Am, the overlap: 83% for Hc and 78% for Am, the maximal distance: 6mm for Hc and 4.4mm for Am. We conclude that the performance of the proposed method compares favourably with that of other published approaches in terms of accuracy and has a short execution time.

  9. Interrelations of Down Syndrome and Alzheimer Disease. ARC Facts.

    ERIC Educational Resources Information Center

    Schweber, Miriam

    This fact sheet summarizes the interrelations of Down syndrome and Alzheimer disease in a question and answer format. The following questions are addressed: What is Alzheimer disease? Why is a relationship suggested between Down syndrome and Alzheimer disease? Is there a genetic link between Alzheimer disease and Down syndrome? Why is a…

  10. [Non-drug-based management of Alzheimer's disease].

    PubMed

    de Sant'Anna, Martha; Morat, Brune

    2013-01-01

    Alzheimer's disease requires specific patient management. This can involve non-drug-based treatments such as a cognitive stimulation programme to reinforce the patient's skills. By offering a combination of information and training to the family and caregivers, the patient's quality of life can be improved.

  11. Diagnosis and treatment of Alzheimer's disease.

    PubMed

    Grossberg, George T

    2003-01-01

    The defining characteristic of Alzheimer's disease is cognitive impairment, but commonly this impairment is accompanied by mood and behavioral symptoms such as depression, anxiety, irritability, inappropriate behavior, sleep disturbance, psychosis, and agitation. The symptoms of Alzheimer's disease are not normative to the aging process. Diagnosis of Alzheimer's disease in the majority of cases can be made with confidence through office-based clinical assessment and informant interview. Alzheimer's disease is the most common of the dementing disorders and is exponentially increasing in incidence, projected to affect 8.64 million people in the United States by the year 2047. At present, no treatment can prevent or cure Alzheimer's disease, and the fact that Alzheimer's affects a geriatric population makes treatment all the more challenging. Therapies that could delay onset of symptoms even briefly would have a major impact on public health. As the prevalence of Alzheimer's disease increases, researchers are examining the efficacy of treatment options beyond the realm of the established cholinesterase inhibitors.

  12. Targeting the Endocannabinoid System in Alzheimer's Disease

    PubMed Central

    Koppel, Jeremy; Davies, Peter

    2010-01-01

    The endocannabinoid system is rapidly emerging as a potential drug target for a variety of immune-mediated central nervous system diseases. There is a growing body of evidence suggesting that endocannabinoid interventions may have particular relevance to Alzheimer's disease. Here we present a review of endocannabinoid physiology, the evidence that underscores its utility as a potential target for intervention in Alzheimer's disease, and suggest future pathways of research. PMID:18997302

  13. Increased BMP6 levels in the brains of Alzheimer's disease patients and APP transgenic mice are accompanied by impaired neurogenesis.

    PubMed

    Crews, Leslie; Adame, Anthony; Patrick, Christina; Delaney, Alexandra; Pham, Emiley; Rockenstein, Edward; Hansen, Lawrence; Masliah, Eliezer

    2010-09-15

    During aging and in the progression of Alzheimer's disease (AD), synaptic plasticity and neuronal integrity are disturbed. In addition to the alterations in plasticity in mature neurons, the neurodegenerative process in AD has been shown to be accompanied by alterations in neurogenesis. Members of the bone morphogenetic protein (BMP) family of growth factors have been implicated as important regulators of neurogenesis and neuronal cell fate determination during development; however, their role in adult neurogenesis and in AD is less clear. We show here by qRT-PCR analysis that BMP6 mRNA levels were significantly increased in the hippocampus of human patients with AD and in APP transgenic mice compared to controls. Immunoblot and immunohistochemical analyses confirmed that BMP6 protein levels were increased in human AD brains and APP transgenic mouse brains compared to controls and accumulated around hippocampal plaques. The increased levels of BMP6 were accompanied by defects in hippocampal neurogenesis in AD patients and APP transgenic mice. In support of a role for BMP6 in defective neurogenesis in AD, we show in an in vitro model of adult neurogenesis that treatment with amyloid-β(1-42) protein (Aβ) resulted in increased expression of BMP6, and that exposure to recombinant BMP6 resulted in reduced proliferation with no toxic effects. Together, these results suggest that Aβ-associated increases in BMP6 expression in AD may have deleterious effects on neurogenesis in the hippocampus, and therapeutic approaches could focus on normalization of BMP6 levels to protect against AD-related neurogenic deficits.

  14. Preliminary evidence of altered steroidogenesis in women with Alzheimer's disease: Have the patients "OLDER" adrenal zona reticularis?

    PubMed

    Vaňková, Markéta; Hill, Martin; Velíková, Marta; Včelák, Josef; Vacínová, Gabriela; Dvořáková, Kateřina; Lukášová, Petra; Vejražková, Daniela; Rusina, Robert; Holmerová, Iva; Jarolímová, Eva; Vaňková, Hana; Kancheva, Radmila; Bendlová, Běla; Stárka, Luboslav

    2016-04-01

    Alzheimer's disease (AD) represents more than half of total dementias. Various factors including altered steroid biosynthesis may participate in its pathophysiology. We investigated how the circulating steroids (measured by GC-MS and RIA) may be altered in the presence of AD. Sixteen women with AD and 22 age- and BMI-corresponding controls aged over 65 years were enrolled in the study. The steroid levels (47 steroids and steroid polar conjugates) and their ratios in AD female patients indicated increased CYP11A1 activity, weakened activity of the CYP17A1C17,20 lyase metabolic step and attenuated sulfotransferase SULT2A1 activity at higher activity of the CYP17A1 17-hydroxylase step. The patients showed diminished HSD3B2 activity for C21 steroids, abated conversion of 17-hydroxyprogesterone to cortisol, and significantly elevated cortisol. The women with AD had also attenuated steroid 7α-hydroxylation forming immunoprotective Δ(5)-C19 steroids, attenuated aromatase activity forming estradiol that induces autoimmunity and a shift from the 3β-hydroxy-5α/β-reduced C19 steroids to their neuroinhibitory and antiinflammatory GABAergic 3α-hydroxy- counterparts and showed higher levels of the 3α-hydroxy-5α/β-reduced C21 steroids and pregnenolone sulfate (improves cognitive abilities but may be both protective and excitotoxic). Our preliminary data indicated functioning of alternative "backdoor" pathway in women with AD showing higher levels of both 5α/β-reduced C21 steroids but reduced levels of both 5α/β-reduced C21 steroids, which implied that the alternative "backdoor" pathway might include both 5α- and 5β-reduced steroids. Our study suggested relationships between AD status in women based on the age of subjects and levels of 10 steroids measured by GC-MS.

  15. Memory binding and white matter integrity in familial Alzheimer's disease.

    PubMed

    Parra, Mario A; Saarimäki, Heini; Bastin, Mark E; Londoño, Ana C; Pettit, Lewis; Lopera, Francisco; Della Sala, Sergio; Abrahams, Sharon

    2015-05-01

    Binding information in short-term and long-term memory are functions sensitive to Alzheimer's disease. They have been found to be affected in patients who meet criteria for familial Alzheimer's disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer's disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer's disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer's disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer's disease and their damage is associated with impairments in two memory binding functions known to

  16. Impairments of auditory scene analysis in Alzheimer's disease.

    PubMed

    Goll, Johanna C; Kim, Lois G; Ridgway, Gerard R; Hailstone, Julia C; Lehmann, Manja; Buckley, Aisling H; Crutch, Sebastian J; Warren, Jason D

    2012-01-01

    Parsing of sound sources in the auditory environment or 'auditory scene analysis' is a computationally demanding cognitive operation that is likely to be vulnerable to the neurodegenerative process in Alzheimer's disease. However, little information is available concerning auditory scene analysis in Alzheimer's disease. Here we undertook a detailed neuropsychological and neuroanatomical characterization of auditory scene analysis in a cohort of 21 patients with clinically typical Alzheimer's disease versus age-matched healthy control subjects. We designed a novel auditory dual stream paradigm based on synthetic sound sequences to assess two key generic operations in auditory scene analysis (object segregation and grouping) in relation to simpler auditory perceptual, task and general neuropsychological factors. In order to assess neuroanatomical associations of performance on auditory scene analysis tasks, structural brain magnetic resonance imaging data from the patient cohort were analysed using voxel-based morphometry. Compared with healthy controls, patients with Alzheimer's disease had impairments of auditory scene analysis, and segregation and grouping operations were comparably affected. Auditory scene analysis impairments in Alzheimer's disease were not wholly attributable to simple auditory perceptual or task factors; however, the between-group difference relative to healthy controls was attenuated after accounting for non-verbal (visuospatial) working memory capacity. These findings demonstrate that clinically typical Alzheimer's disease is associated with a generic deficit of auditory scene analysis. Neuroanatomical associations of auditory scene analysis performance were identified in posterior cortical areas including the posterior superior temporal lobes and posterior cingulate. This work suggests a basis for understanding a class of clinical symptoms in Alzheimer's disease and for delineating cognitive mechanisms that mediate auditory scene analysis

  17. Altered Superficial White Matter on Tractography MRI in Alzheimer's Disease

    PubMed Central

    Reginold, William; Luedke, Angela C.; Itorralba, Justine; Fernandez-Ruiz, Juan; Islam, Omar; Garcia, Angeles

    2016-01-01

    Background/Aims Superficial white matter provides extensive cortico-cortical connections. This tractography study aimed to assess the diffusion characteristics of superficial white matter tracts in Alzheimer's disease. Methods Diffusion tensor 3T magnetic resonance imaging scans were acquired in 24 controls and 16 participants with Alzheimer's disease. Neuropsychological test scores were available in some participants. Tractography was performed by the Fiber Assignment by Continuous Tracking (FACT) method. The superficial white matter was manually segmented and divided into frontal, parietal, temporal and occipital lobes. The mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AxD) and fractional anisotropy (FA) of these tracts were compared between controls and participants with Alzheimer's disease and correlated with available cognitive tests while adjusting for age and white matter hyperintensity volume. Results Alzheimer's disease was associated with increased MD (p = 0.0011), increased RD (p = 0.0019) and increased AxD (p = 0.0017) in temporal superficial white matter. In controls, superficial white matter was associated with the performance on the Montreal Cognitive Assessment, Stroop and Trail Making Test B tests, whereas in Alzheimer's disease patients, it was not associated with the performance on cognitive tests. Conclusion Temporal lobe superficial white matter appears to be disrupted in Alzheimer's disease. PMID:27489557

  18. Mouse Models of Alzheimer's Disease.

    PubMed

    Esquerda-Canals, Gisela; Montoliu-Gaya, Laia; Güell-Bosch, Jofre; Villegas, Sandra

    2017-03-10

    Alzheimer's disease (AD) is a neurodegenerative disorder that nowadays affects more than 40 million people worldwide and it is predicted to exponentially increase in the coming decades. Because no curative treatment exists, research on the pathophysiology of the disease, as well as the testing of new drugs, are mandatory. For these purposes, animal models constitute a valuable, although perfectible tool. This review takes a tour through several aspects of mouse models of AD, such as the generation of transgenic models, the relevance of the promoter driving the expression of the transgenes, and the concrete transgenes used to simulate AD pathophysiology. Then, transgenic mouse lines harboring mutated human genes at several loci such as APP, PSEN1, APOEɛ4, and ob (leptin) are reviewed. Therefore, not only the accumulation of the Aβ peptide is emulated but also cholesterol and insulin metabolism. Further novel information about the disease will allow for the development of more accurate animal models, which in turn will undoubtedly be helpful for bringing preclinical research closer to clinical trials in humans.

  19. Insulin Resistance in Alzheimer's Disease

    PubMed Central

    Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

    2014-01-01

    Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. PMID:25237037

  20. Alzheimer's disease and epigenetic diet.

    PubMed

    Sezgin, Zeynep; Dincer, Yildiz

    2014-12-01

    Alzheimer's disease (AD) is the most common neurodegenerative disease. Many efforts have been directed to prevent AD due to its rising prevalence and the lack of an effective curative treatment. Various epigenetic mechanisms are linked to pathogenesis of AD. Epigenetic alterations may occur through external factors and are known for their reversibility. Dietary factors can influence epigenetic mechanisms. Several neuroprotective nutrients have been shown to enhance cognition, memory and other impaired functions seen in AD. Within recent years neuroprotective nutrients have gained more attention in the field of epigenetic. A growing body of evidence suggest that epigenetic changes triggered by dietary nutrients have an important role in health and in prevention of some diseases, especially neurodegenerative disorders. Several studies have shown that folic acid, vitamin B12, choline, zinc, selenium, dietary polyphenols are capable of interacting with epigenetic mechanisms and ultimately gene expression. Epigenetic mechanisms resulting in neuronal dysfunction may be modified by diet. Therefore manipulation of epigenetic mechanisms via dietary nutrients may affect influence the vulnerability of neurons to degeneration which is seen in AD. The aim of this article is to provide a brief overview about the recent findings related to epigenetic alterations that are linked to AD pathogenesis, and to discuss the bioactive nutrients which can affect these epigenetic mechanisms.

  1. Novel therapeutics for Alzheimer's disease: an update.

    PubMed

    Bonda, David J; Lee, Hyun-Pil; Lee, Hyoung-gon; Friedlich, Avi L; Perry, George; Zhu, Xiongwei; Smith, Mark A

    2010-03-01

    As the most prevalent form of dementia worldwide, Alzheimer's disease (AD) continues to be a burden for patients and their families. In addition, with the global population of aged individuals increasing exponentially, AD represents a significant economic burden to society. The development of an effective approach for the treatment of AD is thus of major importance, as current treatment strategies are limited to agents that attenuate disease symptomatology without addressing the causes of disease. A considerable need exists for the development of an effective therapy to prevent, or at least delay, the progression of AD. Current hypotheses for the pathogenesis of AD are discussed in this review, with a particular emphasis on the implications of these hypotheses with respect to treatment strategies and preventive measures.

  2. How does diabetes accelerate Alzheimer disease pathology?

    PubMed Central

    Sims-Robinson, Catrina; Kim, Bhumsoo; Rosko, Andrew; Feldman, Eva L.

    2011-01-01

    Diabetes and Alzheimer disease (AD)—two age-related diseases—are both increasing in prevalence, and numerous studies have demonstrated that patients with diabetes have an increased risk of developing AD compared with healthy individuals. The underlying biological mechanisms that link the development of diabetes with AD are not fully understood. Abnormal protein processing, abnormalities in insulin signaling, dysregulated glucose metabolism, oxidative stress, the formation of advanced glycation end products, and the activation of inflammatory pathways are features common to both diseases. Hypercholesterolemia is another factor that has received attention, owing to its potential association with diabetes and AD. This Review summarizes the mechanistic pathways that might link diabetes and AD. An understanding of this complex interaction is necessary for the development of novel drug therapies and lifestyle guidelines aimed at the treatment and/or prevention of these diseases. PMID:20842183

  3. Parkinson's disease and Alzheimer's disease: hypersensitivity to X rays in cultured cell lines.

    PubMed Central

    Robbins, J H; Otsuka, F; Tarone, R E; Polinsky, R J; Brumback, R A; Nee, L E

    1985-01-01

    Fibroblast and/or lymphoblastoid lines from patients with several inherited primary neuronal degenerations are hypersensitive to DNA-damaging agents. Therefore, lymphoblastoid lines were irradiated from patients with sporadic Parkinson's disease (PD), Alzheimer's disease, and amyotrophic lateral sclerosis. The mean survival values of the eight Parkinson's disease and of the six Alzheimer's disease lines, but not of the five amyotrophic lateral sclerosis lines, were less than that of the 28 normal lines. Our results with Parkinson's disease and Alzheimer's disease cells can be explained by a genetic defect arising as a somatic mutation during embryogenesis, causing defective repair of the X-ray type of DNA damage. Such a DNA repair defect could cause an abnormal accumulation of spontaneously occurring DNA damage in Parkinson's disease and Alzheimer's disease neurons in vivo, resulting in their premature death. PMID:3876409

  4. Characteristics of Forensic Patients in California With Dementia/Alzheimer's Disease.

    PubMed

    Bartos, Bradley J; Renner, Matthew; Newark, Carol; McCleary, Richard; Scurich, Nicholas

    2017-03-28

    Criminal defendants found incompetent to stand trial (IST) are sent to state hospitals for treatment to be restored to competency. IST patients diagnosed with dementia and related disorders present a particular challenge to clinicians, because they must be restored successfully within a statutorily mandated time frame (e.g., 3 years in California for defendants charged with a felony offense). This study examined a comprehensive data set that included all forensic patients served by California's Department of State Hospitals from September 2003 to February 2016. The findings revealed that, although most IST patients with a dementia diagnosis were restored to competency within the statutory time frames, they spent, on average, over twice as long confined than IST patients without a dementia diagnosis and were less likely than the latter group to be successfully restored. One implication of these findings is that forensic clinicians ought to assess whether IST patients diagnosed with dementia are likely to be restored or not as early as possible in the evaluation and triage process and report to the court any IST patients with a dementia diagnosis who are unlikely to be restored successfully. This would both prevent such patients from gratuitous confinement as well as free up treatment resources for other patients.

  5. Hippocampal atrophy rates in Alzheimer disease

    PubMed Central

    Henneman, W J.P.; Sluimer, J D.; Barnes, J; van der Flier, W M.; Sluimer, I C.; Fox, N C.; Scheltens, P; Vrenken, H; Barkhof, F

    2009-01-01

    Objective: To investigate the added value of hippocampal atrophy rates over whole brain volume measurements on MRI in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and controls. Methods: We included 64 patients with AD (67 ± 9 years; F/M 38/26), 44 patients with MCI (71 ± 6 years; 21/23), and 34 controls (67 ± 9 years; 16/18). Two MR scans were performed (scan interval: 1.8 ± 0.7 years; 1.0 T), using a coronal three-dimensional T1-weighted gradient echo sequence. At follow-up, 3 controls and 23 patients with MCI had progressed to AD. Hippocampi were manually delineated at baseline. Hippocampal atrophy rates were calculated using regional, nonlinear fluid registration. Whole brain baseline volumes and atrophy rates were determined using automated segmentation and registration tools. Results: All MRI measures differed between groups (p < 0.005). For the distinction of MCI from controls, larger effect sizes of hippocampal measures were found compared to whole brain measures. Between MCI and AD, only whole brain atrophy rate differed significantly. Cox proportional hazards models (variables dichotomized by median) showed that within all patients without dementia, hippocampal baseline volume (hazard ratio [HR]: 5.7 [95% confidence interval: 1.5–22.2]), hippocampal atrophy rate (5.2 [1.9–14.3]), and whole brain atrophy rate (2.8 [1.1–7.2]) independently predicted progression to AD; the combination of low hippocampal volume and high atrophy rate yielded a HR of 61.1 (6.1–606.8). Within patients with MCI, only hippocampal baseline volume and atrophy rate predicted progression. Conclusion: Hippocampal measures, especially hippocampal atrophy rate, best discriminate mild cognitive impairment (MCI) from controls. Whole brain atrophy rate discriminates Alzheimer disease (AD) from MCI. Regional measures of hippocampal atrophy are the strongest predictors of progression to AD. GLOSSARY AD = Alzheimer disease; BET = brain

  6. New cardiovascular targets to prevent late onset Alzheimer disease.

    PubMed

    Claassen, Jurgen A H R

    2015-09-15

    The prevalence of dementia rises to between 20% and 40% with advancing age. The dominant cause of dementia in approximately 70% of these patients is Alzheimer disease. There is no effective disease-modifying pharmaceutical treatment for this neurodegenerative disease. A wide range of Alzheimer drugs that appeared effective in animal models have recently failed to show clinical benefit in patients. However, hopeful news has emerged from recent studies that suggest that therapeutic strategies aimed at reducing cardiovascular disease may also reduce the prevalence of dementia due to Alzheimer disease. This review summarizes the evidence for this link between cardiovascular disease and late onset Alzheimer dementia. Only evidence from human research is considered here. Longitudinal studies show an association between high blood pressure and pathological accumulation of the protein amyloid-beta42, and an even stronger association between vascular stiffness and amyloid accumulation, in elderly subjects. Amyloid-beta42 accumulation is considered to be an early marker of Alzheimer disease, and increases the risk of subsequent cognitive decline and development of dementia. These observations could provide an explanation for recent observations of reduced dementia prevalence associated with improved cardiovascular care.

  7. Economic cost of Alzheimer disease in Israel.

    PubMed

    Beeri, Michal Schnaider; Werner, Perla; Adar, Zvi; Davidson, Michael; Noy, Shlomo

    2002-01-01

    The objective of this prospective study was to evaluate the cost of Alzheimer disease (AD) in Israel. Seventy-one AD patients who lived in the community, 50 institutionalized AD patients, both AD groups' respective primary caregivers, and 50 healthy elderly subjects were interviewed. The interviews covered information about the number of caregivers' hours invested in caring for the patient and amount of expenditures such as in house paid help and payments for day care. The annual social cost of caring for a person with AD in Israel was approximately $17,000, whether the patient lived at home or in a nursing home, but the cost components differed in the two groups. For community-dwelling patients, 60% of the cost represented an imputed value of unpaid indirect care compared with 12% for institutionalized patients. Also, in both residences, the private cost was significantly higher than the public cost, i.e., more 75% of the services provided to patients were paid out of pocket. Cost of institutionalization was the major component of the social cost. The cost of the disease increased with functional and cognitive deterioration for the community-dwelling group only. With projected increases in the number of persons at risk for developing AD, the economic impact of the disease on future costs will be significant. Efforts to delay deterioration and, as a result, delay institutionalization seem crucial for cost containment.

  8. Galantamine Response Associates with Agitation and the Prefrontal Cortex in Patients with Alzheimer's Disease.

    PubMed

    Nakayama, Sachiko; Suda, Akimitsu; Nakanishi, Atsushi; Motoi, Yumiko; Hattori, Nobutaka

    2017-01-01

    Behavioral and psychological symptoms of dementia (BPSD) occur in up to 80% of AD patients and represent one of the largest factors contributing to caregiver burden. To analyze the effect of galantamine on BPSD and caregiver burden, we treated a total of 50 patients with mild AD for 12 weeks and evaluated them using the Neuropsychiatric Inventory (NPI) and Japanese version of the Zarit Caregiver Burden Interview (ZBI). We also performed regional cerebral blood flow single photon emission computed tomography (rCBF SPECT) at baseline using three-dimensional sterotatic surface projections. Total NPI and ZBI scores did not significantly change after 12-week galantamine treatment. To identify the characteristics of patients who showed improvement after galantamine treatment, we divided patients into two groups, those with and those without sub-items on the NPI. Patients with aggression showed improvement in ZBI scores (p < 0.05). A comparison of rCBF SPECT between these two groups indicated that patients with aggression exhibited increased rCBF in the right prefrontal cortex compared with those without aggression. In a patient with aggression, 20-month treatment with galantamine inhibited increases in the rCBF area in the right prefrontal lobe. These results suggest that galantamine response may be related to aggression and dysfunction of the prefrontal cortex.

  9. Perspectives on the etiology of Alzheimer's disease

    SciTech Connect

    Mozar, H.N.; Bal, D.G.; Howard, J.T.

    1987-03-20

    There is a lack of consensus among investigators concerning the etiology of Alzheimer's disease. Clues are lacking, however, and the authors have assessed them in a broad biologic context. This inquiry has led us to regard Alzheimer's disease as a multifactorial disorder in which a putative infective agent is an essential element. Despite seeming competition among current hypotheses, there is overall unity. The concept that Down's syndrome is a congenital form of Alzheimer's disease and that both conditions are the result of a ubiquitous infective pathogen that affects genetically susceptible individuals offers the broadest unification. In both conditions slow infections develops against the background of aging. Indirect evidence involving immunologic and other biologic phenomena supports the postulated infectious origin. Overlapping pathologic and clinical features of Alzheimer's disease and the known transmissible encephalopathies suggest a similar pathogenesis.

  10. Global data sharing in Alzheimer's disease research

    PubMed Central

    Toga, Arthur W.; Bhatt, Priya; Ashish, Naveen

    2015-01-01

    Many investigators recognize the importance of data sharing, however they lack the capability to share data. Research efforts could be vastly expanded if Alzheimer's disease data from around the world was linked by a global infrastructure that would enable scientists to access and utilize a secure network of data with thousands of study participants at risk for or already suffering from the disease. We discuss the benefits of data sharing, impediments today and solutions to achieving this on a global scale. We introduce the Global Alzheimer's Association Interactive Network (GAAIN), a novel approach to create a global network of Alzheimer's disease data, researchers, analytical tools and computational resources to better our understanding of this debilitating condition. GAAIN has addressed the key impediments to Alzheimer's disease data sharing with its model and approach. It presents practical, promising, yet data owner sensitive data sharing solutions. PMID:26523713

  11. Periodontitis and Cognitive Decline in Alzheimer's Disease.

    PubMed

    Ide, Mark; Harris, Marina; Stevens, Annette; Sussams, Rebecca; Hopkins, Viv; Culliford, David; Fuller, James; Ibbett, Paul; Raybould, Rachel; Thomas, Rhodri; Puenter, Ursula; Teeling, Jessica; Perry, V Hugh; Holmes, Clive

    2016-01-01

    Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.

  12. Alzheimer disease and genetics: anticipating the questions.

    PubMed

    Schutte, Debra L

    2006-12-01

    Three genes with autosomal dominant mutations have been identified that may lead to Alzheimer symptoms in carriers before they reach age 60. Genetic tests exist for Alzheimer disease, but they are considered useful only for the small number of families with a history of early-onset illness. As researchers continue to uncover evidence of genetic links to Alzheimer disease, nurses can expect to field questions from family members about genetic testing. The article presents a variety of questions nurses may be asked, as well as possible answers.

  13. Alzheimer's disease: research advances and medical reality.

    PubMed

    Seiguer, Erica

    2005-07-01

    Alzheimer's disease was the eighth-leading cause of death in 2001. There is no cure and no effective treatment. Alzheimer's disease presents policy-makers with several challenges, including the level of funding and direction of federally funded research, as well as the cost pressures on Medicare and Medicaid of long-term care. These challenges will increase in intensity as demographic changes, particularly the aging of baby boomers, take hold. Better prevention of Alzheimer's, advances in therapy, and appropriate care modalities will likely require significant investment.

  14. Randomized controlled trials for Alzheimer disease and Parkinson disease.

    PubMed

    Lauretani, Fulvio; Ticinesi, Andrea; Meschi, Tiziana; Teresi, Giulio; Ceda, Gian Paolo; Maggio, Marcello

    2016-06-01

    The continuous increase in elderly and oldest-old population, and subsequent rise in prevalence of chronic neurological diseases like Alzheimer's disease (AD) and Parkinson's disease (PD), are a major challenge for healthcare systems. These two conditions are the most prevalent neurodegenerative diseases in older persons and physicians should engage treatment for these patients. In this field, Randomized Clinical Trials (RCTs) specifically focused on elderly populations are still lacking. The aim of this study was to identify RCTs conducted among AD and PD and to examine the difference between mean age of enrollment and incidence of these two neurodegenerative diseases. We found that the scenario is different between PD and AD. In particular, the enrollment for PD trials seems to include younger persons than AD, although the incidence of both diseases is similar and highest after 80 years old. The consequence of these results could influence conclusive guidelines of treatment in older parkinsonian patients.

  15. Alzheimer's Disease and Prion Protein

    PubMed Central

    Zhou, Jiayi; Liu, Bingqian

    2013-01-01

    Summary Alzheimer's disease (AD) is a devastating neurodegenerative disease with progressive loss of memory and cognitive function, pathologically hallmarked by aggregates of the amyloid-beta (Aβ) peptide and hyperphosphorylated tau in the brain. Aggregation of Aβ under the form of amyloid fibrils has long been considered central to the pathogenesis of AD. However, recent evidence has indicated that soluble Aβ oligomers, rather than insoluble fibrils, are the main neurotoxic species in AD. The cellular prion protein (PrPC) has newly been identified as a cell surface receptor for Aβ oligomers. PrPC is a cell surface glycoprotein that plays a key role in the propagation of prions, proteinaceous infectious agents that replicate by imposing their abnormal conformation to PrPC molecules. In AD, PrPC acts to transduce the neurotoxic signals arising from Aβ oligomers, leading to synaptic failure and cognitive impairment. Interestingly, accumulating evidence has also shown that aggregated Aβ or tau possesses prion-like activity, a property that would allow them to spread throughout the brain. In this article, we review recent findings regarding the function of PrPC and its role in AD, and discuss potential therapeutic implications of PrPC-based approaches in the treatment of AD. PMID:25343100

  16. Effects of Cognitive-Communication Stimulation for Alzheimer's Disease Patients Treated with Donepezil.

    ERIC Educational Resources Information Center

    Chapman, Sandra Bond; Weiner, Myron F.; Rackley, Audette; Hynan, Linda S.; Zientz, Jennifer

    2004-01-01

    ds to growing evidence that active cognitive stimulation may slow the rate of verbal and functional decline and decrease negative emotional symptoms in AD when combined with acetylcholinesterase inhibitors, indicating a need to advance research in the area of cognitive treatments. The fact that AD is a progressive brain disease should not preclude…

  17. Alzheimer's Disease. LC Science Tracer Bullet 87-2.

    ERIC Educational Resources Information Center

    Sammons, Vivian O., Comp.

    Alzheimer's disease is characterized by a degeneration and shrinkage of brain tissue; the symptoms include progressive memory loss, bizarre behavior, difficulty in speaking and walking, incontinence, and confusion. Positive diagnosis is possible only upon examination of brain tissue at autopsy. The disease affects not only the patient but also the…

  18. Studies of Implicit Prototype Extraction in Patients with Mild Cognitive Impairment and Early Alzheimer's Disease

    ERIC Educational Resources Information Center

    Nosofsky, Robert M.; Denton, Stephen E.; Zaki, Safa R.; Murphy-Knudsen, Anne F.; Unverzagt, Frederick W.

    2012-01-01

    Studies of incidental category learning support the hypothesis of an implicit prototype-extraction system that is distinct from explicit memory (Smith, 2008). In those studies, patients with explicit-memory impairments due to damage to the medial-temporal lobe performed normally in implicit categorization tasks (Bozoki, Grossman, & Smith, 2006;…

  19. Effects of body weight on tolerability of rivastigmine transdermal patch: a post-hoc analysis of a double-blind trial in patients with Alzheimer disease.

    PubMed

    Lee, Jae-Hong; Sevigny, Jeff

    2011-01-01

    The rationale for the development of the rivastigmine transdermal patch was to improve upon an efficacious therapy by mitigating certain adverse events, such as nausea and vomiting. This may be particularly important in Alzheimer disease patients with low body weights, who may be more susceptible to these adverse events. This analysis compared the effect of body weight on tolerability in Alzheimer disease patients receiving rivastigmine capsules or rivastigmine patch. Using data from a 24-week trial, adverse events and discontinuations were evaluated in patients stratified on the basis of extreme low weight (<50 kg), medium weight (50 to 80 kg), and high weight (>80 kg) at baseline. Rivastigmine patch was generally well tolerated, regardless of patient body weight. Among patients receiving rivastigmine patch, lower body weight, as stratified, was not associated with a higher adverse event rate; however, there was an association between a higher adverse event rate and low body weight among patients receiving rivastigmine capsules. Discontinuations because of adverse events were not directly related to weight. A lower incidence of adverse events was apparent with transdermal delivery of rivastigmine compared with oral administration.

  20. Psychometric properties of Malay neuropsychiatry unit cognitive assessment tool among Alzheimer's disease patients in comparison to Malay Montreal Cognitive Assessment.

    PubMed

    Thong, Kai Shin; Chee, Kok Yoon; Ng, Chong Guan; Walterfang, Mark; Velakoulis, Dennis

    2016-09-01

    This study aims to establish psychometric properties of the Malay Neuropsychiatry Unit Cognitive Assessment Tool (Malay NuCOG) in Alzheimer's disease. NuCOG was translated to Malay language and compared with Montreal Cognitive Assessment Tool on 80 individuals. The Malay NuCOG showed good internal consistency and reliability (Cronbach's alpha = 0.895). It demonstrated 100% sensitivity and 87.5% specificity at the cutoff score of 78.50/100. The Malay NuCOG is a valid and reliable cognitive instrument that is sensitive and specific for the detection of dementia and has clinical advantages in its ability to examine individual cognitive domains.

  1. 2016 Alzheimer's disease facts and figures.

    PubMed

    2016-04-01

    This report describes the public health impact of Alzheimer's disease, including incidence and prevalence, mortality rates, costs of care, and the overall impact on caregivers and society. It also examines in detail the financial impact of Alzheimer's on families, including annual costs to families and the difficult decisions families must often make to pay those costs. An estimated 5.4 million Americans have Alzheimer's disease. By mid-century, the number of people living with Alzheimer's disease in the United States is projected to grow to 13.8 million, fueled in large part by the aging baby boom generation. Today, someone in the country develops Alzheimer's disease every 66 seconds. By 2050, one new case of Alzheimer's is expected to develop every 33 seconds, resulting in nearly 1 million new cases per year. In 2013, official death certificates recorded 84,767 deaths from Alzheimer's disease, making it the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age ≥ 65 years. Between 2000 and 2013, deaths resulting from stroke, heart disease, and prostate cancer decreased 23%, 14%, and 11%, respectively, whereas deaths from Alzheimer's disease increased 71%. The actual number of deaths to which Alzheimer's disease contributes is likely much larger than the number of deaths from Alzheimer's disease recorded on death certificates. In 2016, an estimated 700,000 Americans age ≥ 65 years will die with Alzheimer's disease, and many of them will die because of the complications caused by Alzheimer's disease. In 2015, more than 15 million family members and other unpaid caregivers provided an estimated 18.1 billion hours of care to people with Alzheimer's and other dementias, a contribution valued at more than $221 billion. Average per-person Medicare payments for services to beneficiaries age ≥ 65 years with Alzheimer's disease and other dementias are more than two and a half times as great as payments for all

  2. Music Enhances Autobiographical Memory in Mild Alzheimer's Disease

    ERIC Educational Resources Information Center

    El Haj, Mohamad; Postal, Virginie; Allain, Philippe

    2012-01-01

    Studies have shown that the "Four Seasons" music may enhance the autobiographical performance of Alzheimer's disease (AD) patients. We used a repeated measures design in which autobiographical recall of 12 mild AD patients was assessed using a free narrative method under three conditions: (a) in "Silence," (b) after being exposed to the opus "Four…

  3. Awareness of Deficit in Alzheimer's Disease: Relation to Caregiver Burden.

    ERIC Educational Resources Information Center

    Seltzer, Benjamin; And Others

    1997-01-01

    Analyzes caregiver burden in relation to Alzheimer patients' awareness of their own deficits. Results suggest that caregiver burden was associated with impaired patient awareness of memory deficit independent of disease stage and dementia severity, suggesting that impaired awareness may be an important mediator of caregiver burden. (RJM)

  4. Metabolic profiling distinguishes three subtypes of Alzheimer's disease

    PubMed Central

    Bredesen, Dale E.

    2015-01-01

    The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report that metabolic profiling reveals three Alzheimer's disease subtypes. The first is inflammatory, in which markers such as hs-CRP and globulin:albumin ratio are increased. The second type is non-inflammatory, in which these markers are not increased, but other metabolic abnormalities are present. The third type is a very distinctive clinical entity that affects relatively young individuals, extends beyond the typical Alzheimer's disease initial distribution to affect the cortex widely, is characterized by early non-amnestic features such as dyscalculia and aphasia, is often misdiagnosed or labeled atypical Alzheimer's disease, typically affects ApoE4-negative individuals, and is associated with striking zinc deficiency. Given the involvement of zinc in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling, this syndrome of Alzheimer's-plus with low zinc (APLZ) warrants further metabolic, genetic, and epigenetic characterization. PMID:26343025

  5. Validation of Suspected Somatic Single Nucleotide Variations in the Brain of Alzheimer's Disease Patients.

    PubMed

    Gomez-Ramos, Alberto; Picher, Angel J; García, Esther; Garrido, Patricia; Hernandez, Felix; Soriano, Eduardo; Avila, Jesús

    2017-01-01

    Next-generation sequencing techniques and genome-wide association study analyses have provided a huge amount of data, thereby enabling the identification of DNA variations and mutations related to disease pathogenesis. New techniques and software tools have been developed to improve the accuracy and reliability of this identification. Most of these tools have been designed to discover and validate single nucleotide variants (SNVs). However, in addition to germ-line mutations, human tissues bear genomic mosaicism, which implies that somatic events are present only in low percentages of cells within a given tissue, thereby hindering the validation of these variations using standard genetic tools. Here we propose a new method to validate some of these somatic mutations. We combine a recently developed software with a method that cuts DNA by using restriction enzymes at the sites of the variation. The non-cleaved molecules, which bear the SNV, can then be amplified and sequenced using Sanger's technique. This procedure, which allows the detection of alternative alleles present in as few as 10% of cells, could be of value for the identification and validation of low frequency somatic events in a variety of tissues and diseases.

  6. Hippocampal shape analysis in Alzheimer's disease using functional data analysis.

    PubMed

    Epifanio, Irene; Ventura-Campos, Noelia

    2014-02-28

    The hippocampus is one of the first affected regions in Alzheimer's disease. The left hippocampi of control subjects, patients with mild cognitive impairment and patients with Alzheimer's disease are represented by spherical harmonics. Functional data analysis is used in the hippocampal shape analysis. Functional principal component analysis and functional independent component analysis are defined for multivariate functions with two arguments. A functional linear discriminant function is also defined. Comparisons with other approaches are carried out. Our functional approach gives promising results, especially in shape classification.

  7. Deconstructing mitochondrial dysfunction in Alzheimer disease.

    PubMed

    García-Escudero, Vega; Martín-Maestro, Patricia; Perry, George; Avila, Jesús

    2013-01-01

    There is mounting evidence showing that mitochondrial damage plays an important role in Alzheimer disease. Increased oxygen species generation and deficient mitochondrial dynamic balance have been suggested to be the reason as well as the consequence of Alzheimer-related pathology. Mitochondrial damage has been related to amyloid-beta or tau pathology or to the presence of specific presenilin-1 mutations. The contribution of these factors to mitochondrial dysfunction is reviewed in this paper. Due to the relevance of mitochondrial alterations in Alzheimer disease, recent works have suggested the therapeutic potential of mitochondrial-targeted antioxidant. On the other hand, autophagy has been demonstrated to play a fundamental role in Alzheimer-related protein stress, and increasing data shows that this pathway is altered in the disease. Moreover, mitochondrial alterations have been related to an insufficient clearance of dysfunctional mitochondria by autophagy. Consequently, different approaches for the removal of damaged mitochondria or to decrease the related oxidative stress in Alzheimer disease have been described. To understand the role of mitochondrial function in Alzheimer disease it is necessary to generate human cellular models which involve living neurons. We have summarized the novel protocols for the generation of neurons by reprogramming or direct transdifferentiation, which offer useful tools to achieve this result.

  8. REVIEW: Curcumin and Alzheimer's disease.

    PubMed

    Hamaguchi, Tsuyoshi; Ono, Kenjiro; Yamada, Masahito

    2010-10-01

    Curcumin has a long history of use as a traditional remedy and food in Asia. Many studies have reported that curcumin has various beneficial properties, such as antioxidant, antiinflammatory, and antitumor. Because of the reported effects of curcumin on tumors, many clinical trials have been performed to elucidate curcumin's effects on cancers. Recent reports have suggested therapeutic potential of curcumin in the pathophysiology of Alzheimer's disease (AD). In in vitro studies, curcumin has been reported to inhibit amyloid-β-protein (Aβ) aggregation, and Aβ-induced inflammation, as well as the activities of β-secretase and acetylcholinesterase. In in vivo studies, oral administration of curcumin has resulted in the inhibition of Aβ deposition, Aβ oligomerization, and tau phosphorylation in the brains of AD animal models, and improvements in behavioral impairment in animal models. These findings suggest that curcumin might be one of the most promising compounds for the development of AD therapies. At present, four clinical trials concerning the effects of curcumin on AD has been conducted. Two of them that were performed in China and USA have been reported no significant differences in changes in cognitive function between placebo and curcumin groups, and no results have been reported from two other clinical studies. Additional trials are necessary to determine the clinical usefulness of curcumin in the prevention and treatment of AD.

  9. Chronobiological approaches to Alzheimer's disease.

    PubMed

    Stranahan, Alexis M

    2012-01-01

    Dynamic circadian rhythms contribute to memory formation, and the hormonal and neurochemical changes that follow circadian patterns are frequently dysregulated with aging. The effect of aging on circadian rhythms is a double-edged sword; on one hand, poor sleep quality compromises neuronal structure and function in regions that support cognition, and on the other hand, perturbation of central and peripheral oscillators changes the hormonal milieu, with consequences for neuroplasticity. In the current review, recent developments surrounding the circadian regulation of memory formation are described, with reference to how mechanisms that support temporal coding might change with advancing age. The cognitive consequences of changes in sleep patterns are also discussed. New roles for the circadian clock genes period-1, period-2, and bmal1 in memory formation are discussed in the context of age-related cognitive decline. The potential for chronobiological approaches to the treatment and prevention of Alzheimer's disease merits further exploration from a pharmacotherapeutic perspective, as the timing of drug delivery could potentiate or diminish treatment efficacy.

  10. Alzheimer's Disease in Down Syndrome

    PubMed Central

    Head, Elizabeth; Powell, David; Gold, Brian T.; Schmitt, Frederick A.

    2013-01-01

    SUMMARY A key challenge to adults with Down syndrome (DS) as they age is an increased risk for cognitive decline, dementia, and Alzheimer disease (AD). In DS persons ranging from 40-49 years of age, 5.7-55% may be clinically demented and between 50-59 years, dementia prevalence ranges from 4-55% (reviewed in [1]). Despite the wide ranges reported for dementia prevalence, a consistent feature of aging in DS is the progressive accumulation of AD brain pathologies. By the age of 40 years, virtually all have sufficient senile plaques and neurofibrillary tangles for a neuropathological diagnosis of AD [2]. Thus, there is dissociation between the age of onset of AD neuropathology (40 years) and increasing signs of clinical dementia. We discuss the hypothesis that frontal impairments are a critical factor affecting cognitive function and are associated with white matter (WM) and AD neuropathology. While these may be an early sign of conversion to dementia, we also review several other clinical comorbidities that may also contribute to dementia onset. PMID:25285303

  11. Decreased dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) concentrations in plasma of Alzheimer's disease (AD) patients.

    PubMed

    Aldred, Sarah; Mecocci, Patrizia

    2010-01-01

    DHEA is secreted by the adrenal cortex and is also a neurosteroid. Its sulfate (DHEAS) is the most abundant steroid in circulation. The levels of both are seen to decline in concentration with age. Evidence is available for altered levels of DHEA and DHEAS in AD but is limited to relatively few studies assessing small cohorts. This study assessed plasma DHEA and DHEAS levels in AD sufferers (n=72) and compared them to age-matched controls (n=72). Plasma DHEA concentrations were significantly lower in AD patients compared to control (4.24+/-0.4 ng/ml for AD; 3.38+/-0.3 ng/ml for control, p=0.027, Mann-Whitney 1-tailed) and DHEA levels were significantly correlated to DHEAS levels in both control and AD conditions (Spearman's rho correlation coefficient=0.635 in controls and 0.467 in AD, ppatients suffering from AD when compared to age-matched controls.

  12. Joint Modeling of Transitional Patterns of Alzheimer's Disease

    PubMed Central

    Liu, Wei; Zhang, Bo; Zhang, Zhiwei; Zhou, Xiao-Hua

    2013-01-01

    While the experimental Alzheimer's drugs recently developed by pharmaceutical companies failed to stop the progression of Alzheimer's disease, clinicians strive to seek clues on how the patients would be when they visit back next year, based upon the patients' current clinical and neuropathologic diagnosis results. This is related to how to precisely identify the transitional patterns of Alzheimer's disease. Due to the complexities of the diagnosis of Alzheimer's disease, the condition of the disease is usually characterized by multiple clinical and neuropathologic measurements, including Clinical Dementia Rating (CDRGLOB), Mini-Mental State Examination (MMSE), a score derived from the clinician judgement on neuropsychological tests (COGSTAT), and Functional Activities Questionnaire (FAQ). In this research article, we investigate a class of novel joint random-effects transition models that are used to simultaneously analyze the transitional patterns of multiple primary measurements of Alzheimer's disease and, at the same time, account for the association between the measurements. The proposed methodology can avoid the bias introduced by ignoring the correlation between primary measurements and can predict subject-specific transitional patterns. PMID:24073268

  13. Inhalational Alzheimer's disease: an unrecognized—and treatable—epidemic

    PubMed Central

    Bredesen, Dale E.

    2016-01-01

    Alzheimer's disease is one of the most significant healthcare problems today, with a dire need for effective treatment. Identifying subtypes of Alzheimer's disease may aid in the development of therapeutics, and recently three different subtypes have been described: type 1 (inflammatory), type 2 (non-inflammatory or atrophic), and type 3 (cortical). Here I report that type 3 Alzheimer's disease is the result of exposure to specific toxins, and is most commonly inhalational (IAD), a phenotypic manifestation of chronic inflammatory response syndrome (CIRS), due to biotoxins such as mycotoxins. The appropriate recognition of IAD as a potentially important pathogenetic condition in patients with cognitive decline offers the opportunity for successful treatment of a large number of patients whose current prognoses, in the absence of accurate diagnosis, are grave. PMID:26870879

  14. [Advances in the diagnostics of Alzheimer's disease].

    PubMed

    Fiedler, U; Wiltfang, J; Peters, N; Benninghoff, J

    2012-05-01

    Due to the demographic developments, diagnosis and treatment, dementia constitutes an increasing medical challenge and is likely to have an increasing socioeconomic impact. Dementia does not reflect a single disease but encompasses a variety of underlying conditions, heterogeneous clinical courses and therapeutic approaches, among which Alzheimer's disease represents the most common cause. Therefore, a thorough differential diagnosis of dementia is of major importance. To date the current diagnosis of dementia according to ICD-10/DMS-IV is based on clinical criteria. In addition, the concept of mild cognitive impairment comprises early cognitive dysfunction without clinically apparent dementia. Alzheimer's disease is more and more conceptualized as a disease continuum with mild cognitive impairment as an early and manifest dementia as the later stage of the disease. This review gives an overview on the current diagnostic approaches and the proposed revisions of diagnostic and research criteria for Alzheimer's disease.

  15. Graph analysis of verbal fluency test discriminate between patients with Alzheimer's disease, mild cognitive impairment and normal elderly controls

    PubMed Central

    Bertola, Laiss; Mota, Natália B.; Copelli, Mauro; Rivero, Thiago; Diniz, Breno Satler; Romano-Silva, Marco A.; Ribeiro, Sidarta; Malloy-Diniz, Leandro F.

    2014-01-01

    Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment—subtypes amnestic (aMCI) and amnestic multiple domain (a+mdMCI)—and patients with Alzheimer's disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGA). The individuals were compared when divided in three (NC—MCI—AD) and four (NC—aMCI—a+mdMCI—AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the

  16. Graph analysis of verbal fluency test discriminate between patients with Alzheimer's disease, mild cognitive impairment and normal elderly controls.

    PubMed

    Bertola, Laiss; Mota, Natália B; Copelli, Mauro; Rivero, Thiago; Diniz, Breno Satler; Romano-Silva, Marco A; Ribeiro, Sidarta; Malloy-Diniz, Leandro F

    2014-01-01

    Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment-subtypes amnestic (aMCI) and amnestic multiple domain (a+mdMCI)-and patients with Alzheimer's disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGA). The individuals were compared when divided in three (NC-MCI-AD) and four (NC-aMCI-a+mdMCI-AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of

  17. Alzheimer's Disease. Report of the Secretary's Task Force on Alzheimer's Disease.

    ERIC Educational Resources Information Center

    National Inst. of Mental Health (DHHS), Rockville, MD.

    This report of the Health and Human Services Department Task Force on Alzheimer's Disease addresses nine main areas in a problem-oriented approach aimed at better defining research needs and options as well as training, service, and policy issues relevant to Alzheimer's disease. Individual chapters deal with research in the areas of epidemiology,…

  18. Implicit and explicit emotional memory for melodies in Alzheimer's disease and depression.

    PubMed

    Quoniam, Nolwenn; Ergis, Anne-Marie; Fossati, Philippe; Peretz, Isabelle; Samson, Séverine; Sarazin, Marie; Allilaire, Jean-François

    2003-11-01

    The present study investigates the impact of emotional deficits on implicit and explicit memory for musical stimuli in patients with Alzheimer's disease and elderly depressed patients. Results showed that unlike Alzheimer's patients, depressed patients were unable to develop a positive affective bias of judgment for previously heard melodies.

  19. Accumulation of murine amyloid-β mimics early Alzheimer's disease.

    PubMed

    Krohn, Markus; Bracke, Alexander; Avchalumov, Yosef; Schumacher, Toni; Hofrichter, Jacqueline; Paarmann, Kristin; Fröhlich, Christina; Lange, Cathleen; Brüning, Thomas; von Bohlen Und Halbach, Oliver; Pahnke, Jens

    2015-08-01

    Amyloidosis mouse models of Alzheimer's disease are generally established by transgenic approaches leading to an overexpression of mutated human genes that are known to be involved in the generation of amyloid-β in Alzheimer's families. Although these models made substantial contributions to the current knowledge about the 'amyloid hypothesis' of Alzheimer's disease, the overproduction of amyloid-β peptides mimics only inherited (familiar) Alzheimer's disease, which accounts for <1% of all patients with Alzheimer's disease. The inherited form is even regarded a 'rare' disease according to the regulations for funding of the European Union (www.erare.eu). Here, we show that mice that are double-deficient for neprilysin (encoded by Mme), one major amyloid-β-degrading enzyme, and the ABC transporter ABCC1, a major contributor to amyloid-β clearance from the brain, develop various aspects of sporadic Alzheimer's disease mimicking the clinical stage of mild cognitive impairment. Using behavioural tests, electrophysiology and morphological analyses, we compared different ABC transporter-deficient animals and found that alterations are most prominent in neprilysin × ABCC1 double-deficient mice. We show that these mice have a reduced probability to survive, show increased anxiety in new environments, and have a reduced working memory performance. Furthermore, we detected morphological changes in the hippocampus and amygdala, e.g. astrogliosis and reduced numbers of synapses, leading to defective long-term potentiation in functional measurements. Compared to human, murine amyloid-β is poorly aggregating, due to changes in three amino acids at N-terminal positions 5, 10, and 13. Interestingly, our findings account for the action of early occurring amyloid-β species/aggregates, i.e. monomers and small amyloid-β oligomers. Thus, neprilysin × ABCC1 double-deficient mice present a new model for early effects of amyloid-β-related mild cognitive impairment that allows

  20. Assessing impulsivity changes in Alzheimer disease.

    PubMed

    Rochat, Lucien; Delbeuck, Xavier; Billieux, Joël; d'Acremont, Mathieu; Van der Linden, Anne-Claude Juillerat; Van der Linden, Martial

    2008-01-01

    Impulsive behaviors are common in brain-damaged patients including those with neurodegenerative diseases such as Alzheimer disease (AD). The objective of this study was to develop and validate a short version of the UPPS Impulsive Behavior Scale assessing changes on 4 different dimensions of impulsivity, namely urgency, (lack of) premeditation, (lack of) perseverance, and sensation seeking, arising in the course of a neurodegenerative disease. To this end, caregivers of 83 probable AD patients completed a short questionnaire adapted from the UPPS Impulsive Behavior Scale. Exploratory and confirmatory factor analyses of the data were performed and revealed that a model with 4 distinct but related latent variables corresponding to 4 different dimensions of impulsivity fit the data best. Furthermore, the results showed that lack of perseverance, followed by lack of premeditation and urgency, increased after the onset of the disease, whereas sensation seeking decreased. Overall, the multifaceted nature of impulsivity was confirmed in a sample of AD patients, whose caregivers reported significant changes regarding each facet of impulsivity. Consequently, the short version of the UPPS Impulsive Behavior Scale opens up interesting prospects for a better comprehension of behavioral symptoms of dementia.

  1. Stem cell treatment for Alzheimer's disease.

    PubMed

    Li, Ming; Guo, Kequan; Ikehara, Susumu

    2014-10-23

    Alzheimer's disease (AD) is a progressive and neurodegenerative disorder that induces dementia in older people. It was first reported in 1907 by Alois Alzheimer, who characterized the disease as causing memory loss and cognitive impairment. Pathologic characteristics of AD are β-amyloid plaques, neurofibrillary tangles and neurodegeneration. Current therapies only target the relief of symptoms using various drugs, and do not cure the disease. Recently, stem cell therapy has been shown to be a potential approach to various diseases, including neurodegenerative disorders, and in this review, we focus on stem cell therapies for AD.

  2. Alzheimer's Disease therapeutics: current and future therapies.

    PubMed

    Gao, Lin-Ben; Yu, Xiao-Fei; Chen, Qin; Zhou, Dong

    2016-04-01

    Pathologically, Alzheimer's Disease is characterized by amyloidal protein plaques that lead to dementia in the elderly population. While advances have been made in therapeutics over the course of the last 20 years, the drugs generally target the symptoms rather than the underlying pathology. Unfortunately, despite the advances, the mechanisms behind Alzheimer's Disease have still not been clearly identified. Some of these current treatments include acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor agonists. Recently, the pathophysiology behind this disease is becoming more clearly understood and this has led to some novel therapeutic targets that may be able to break the barrier and target the underlying disease. In this review, we will discuss Alzheimer's Disease pathology and the pharmacological therapy that has been in use for a long time as well as novel therapies.

  3. Comparison between Early-Onset and Late-Onset Alzheimer's Disease Patients with Amnestic Presentation: CSF and 18F-FDG PET Study

    PubMed Central

    Chiaravalloti, Agostino; Koch, Giacomo; Toniolo, Sofia; Belli, Lorena; Lorenzo, Francesco Di; Gaudenzi, Sara; Schillaci, Orazio; Bozzali, Marco; Sancesario, Giuseppe; Martorana, Alessandro

    2016-01-01

    Background/Aims To investigate the differences in brain glucose consumption between patients with early onset of Alzheimer's disease (EOAD, aged ≤65 years) and patients with late onset of Alzheimer's disease (LOAD, aged >65 years). Methods Differences in brain glucose consumption between the groups have been evaluated by means of Statistical Parametric Mapping version 8, with the use of age, sex, Mini-Mental State Examination and cerebrospinal fluid values of AΒ1-42, phosphorylated Tau and total Tau as covariates in the comparison between EOAD and LOAD. Results As compared to LOAD, EOAD patients showed a significant decrease in glucose consumption in a wide portion of the left parietal lobe (BA7, BA31 and BA40). No significant differences were obtained when subtracting the EOAD from the LOAD group. Conclusions The results of our study show that patients with EOAD show a different metabolic pattern as compared to those with LOAD that mainly involves the left parietal lobe. PMID:27195000

  4. 78 FR 9396 - Draft Guidance for Industry on Alzheimer's Disease: Developing Drugs for the Treatment of Early...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-08

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Alzheimer's Disease... a draft guidance for industry entitled ``Alzheimer's Disease: Developing Drugs for the Treatment of... demonstrate efficacy in clinical trials in patients in the early stages of Alzheimer's disease that...

  5. Alzheimer's disease research in the context of the national plan to address Alzheimer's disease.

    PubMed

    Snyder, Heather M; Hendrix, James; Bain, Lisa J; Carrillo, Maria C

    2015-01-01

    In 2012, the first National Plan to Address Alzheimer's Disease in the United States (U.S.) was released, a component of the National Alzheimer's Project Act legislation. Since that time, there have been incremental increases in U.S. federal funding for Alzheimer's disease and related dementia research, particularly in the areas of biomarker discovery, genetic link and related biological underpinnings, and prevention studies for Alzheimer's. A central theme in each of these areas has been the emphasis of cross-sector collaboration and private-public partnerships between government, non-profit organizations and for-profit organizations. This paper will highlight multiple private-public partnerships supporting the advancement of Alzheimer's research in the context of the National Plan to Address Alzheimer's.

  6. Resting metabolic connectivity in prodromal Alzheimer's disease. A European Alzheimer Disease Consortium (EADC) project.

    PubMed

    Morbelli, Silvia; Drzezga, Alex; Perneczky, Robert; Frisoni, Giovanni B; Caroli, Anna; van Berckel, Bart N M; Ossenkoppele, Rik; Guedj, Eric; Didic, Mira; Brugnolo, Andrea; Sambuceti, Gianmario; Pagani, Marco; Salmon, Eric; Nobili, Flavio

    2012-11-01

    We explored resting-state metabolic connectivity in prodromal Alzheimer's disease (pAD) patients and in healthy controls (CTR), through a voxel-wise interregional correlation analysis of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) by means of statistical parametric mapping. Baseline 18F-fluorodeoxyglucose-positron emission tomography of 36 patients with amnestic mild cognitive impairment who converted to Alzheimer's disease (AD) dementia after an average time of 2 years (pAD) and of 105 CTR were processed. The area of hypometabolism in pAD showed less metabolic connectivity in patients than in CTR (autocorrelation and correlation with large temporal and frontal areas, respectively). pAD patients showed limited correlation even in selected nonhypometabolic areas, including the hippocampi and the dorsolateral prefrontal cortex (DLFC). On the contrary, in CTR group correlation was highlighted between hippocampi and precuneus/posterior cingulate and frontal cortex, and between dorsolateral prefrontal cortex and caudate nuclei and parietal cortex. The reduced metabolic connections both in hypometabolic and nonhypometabolic areas in pAD patients suggest that metabolic disconnection (reflecting early diaschisis) may antedate remote hypometabolism (early sign of synaptic degeneration).

  7. Advances in Raman spectroscopy for the diagnosis of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Sudworth, Caroline D.; Archer, John K. J.; Black, Richard A.; Mann, David

    2006-02-01

    Within the next 50 years Alzheimer's disease is expected to affect 100 million people worldwide. The progressive decline in the mental health of the patient is caused by severe brain atrophy generated by the breakdown and aggregation of proteins, resulting in β-amyloid plaques and neurofibrillary tangles. The greatest challenge to Alzheimer's disease lies in the pursuit of an early and definitive diagnosis, in order that suitable treatment can be administered. At the present time, definitive diagnosis is restricted to post-mortem examination. Alzheimer's disease also remains without a long-term cure. This research demonstrates the potential role of Raman spectroscopy, combined with principle components analysis (PCA), as a diagnostic method. Analyses of ethically approved ex vivo post-mortem brain tissues (originating from frontal and occipital lobes) from control (3 normal elderly subjects and 3 Huntingdon's disease subjects) and Alzheimer's disease (12 subjects) brain sections, and a further set of 12 blinded samples are presented. Spectra originating from these tissues are highly reproducible, and initial results indicate a vital difference in protein content and conformation, relating to the abnormally high levels of aggregated proteins in the diseased tissues. Further examination of these spectra using PCA allows for the separation of control from diseased tissues. The validation of the PCA models using blinded samples also displays promise for the identification of Alzheimer's disease, in conjunction with secondary information regarding other brain diseases and dementias. These results provide a route for Raman spectroscopy as a possible non-invasive, non-destructive tool for the early diagnosis of Alzheimer's disease.

  8. An EEG-Based Fuzzy Probability Model for Early Diagnosis of Alzheimer's Disease.

    PubMed

    Chiang, Hsiu-Sen; Pao, Shun-Chi

    2016-05-01

    Alzheimer's disease is a degenerative brain disease that results in cardinal memory deterioration and significant cognitive impairments. The early treatment of Alzheimer's disease can significantly reduce deterioration. Early diagnosis is difficult, and early symptoms are frequently overlooked. While much of the literature focuses on disease detection, the use of electroencephalography (EEG) in Alzheimer's diagnosis has received relatively little attention. This study combines the fuzzy and associative Petri net methodologies to develop a model for the effective and objective detection of Alzheimer's disease. Differences in EEG patterns between normal subjects and Alzheimer patients are used to establish prediction criteria for Alzheimer's disease, potentially providing physicians with a reference for early diagnosis, allowing for early action to delay the disease progression.

  9. Alzheimer's disease, apolipoprotein E and hormone replacement therapy.

    PubMed

    Depypere, H; Vierin, A; Weyers, S; Sieben, A

    2016-12-01

    Alzheimer's disease is the most frequent cause of dementia in older patients. The prevalence is higher in women than in men. This may be the result of both the higher life expectancy of women and the loss of neuroprotective estrogen after menopause. Earlier age at menopause (spontaneous or surgical) is associated with an enhanced risk of developing Alzheimer's disease. Therefore, it is postulated that estrogen could be protective against it. If so, increasing exposure to estrogen through the use of postmenopausal hormone replacement could also be protective against Alzheimer's disease. The results of the clinical studies that have examined this hypothesis are inconclusive, however. One explanation for this is that estrogen treatment is protective only if it is initiated in the years immediately after menopause. Another possibility is that the neuroprotective effects of estrogen are negated by a particular genotype of apolipoprotein E. This protein plays an important role in cholesterol transport to the neurons. Studies that have examined the link between estrogen replacement therapy, Alzheimer's disease and the E4 allele of ApoE are inconclusive. This article reviews the literature on the influence of hormone replacement therapy on the incidence and progression of Alzheimer's disease.

  10. Alzheimer's disease; taking the edge off with cannabinoids?

    PubMed Central

    Campbell, V A; Gowran, A

    2007-01-01

    Alzheimer's disease is an age-related neurodegenerative condition associated with cognitive decline. The pathological hallmarks of the disease are the deposition of β-amyloid protein and hyperphosphorylation of tau, which evoke neuronal cell death and impair inter-neuronal communication. The disease is also associated with neuroinflammation, excitotoxicity and oxidative stress. In recent years the proclivity of cannabinoids to exert a neuroprotective influence has received substantial interest as a means to mitigate the symptoms of neurodegenerative conditions. In brains obtained from Alzheimer's patients alterations in components of the cannabinoid system have been reported, suggesting that the cannabinoid system either contributes to, or is altered by, the pathophysiology of the disease. Certain cannabinoids can protect neurons from the deleterious effects of β-amyloid and are capable of reducing tau phosphorylation. The propensity of cannabinoids to reduce β-amyloid-evoked oxidative stress and neurodegeneration, whilst stimulating neurotrophin expression neurogenesis, are interesting properties that may be beneficial in the treatment of Alzheimer's disease. Δ9-tetrahydrocannabinol can also inhibit acetylcholinesterase activity and limit amyloidogenesis which may improve cholinergic transmission and delay disease progression. Targeting cannabinoid receptors on microglia may reduce the neuroinflammation that is a feature of Alzheimer's disease, without causing psychoactive effects. Thus, cannabinoids offer a multi-faceted approach for the treatment of Alzheimer's disease by providing neuroprotection and reducing neuroinflammation, whilst simultaneously supporting the brain's intrinsic repair mechanisms by augmenting neurotrophin expression and enhancing neurogenesis. The evidence supporting a potential role for the cannabinoid system as a therapeutic target for the treatment of Alzheimer's disease will be reviewed herewith. PMID:17828287

  11. Synaptic Cell Adhesion Molecules in Alzheimer's Disease

    PubMed Central

    Leshchyns'ka, Iryna

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative brain disorder associated with the loss of synapses between neurons in the brain. Synaptic cell adhesion molecules are cell surface glycoproteins which are expressed at the synaptic plasma membranes of neurons. These proteins play key roles in formation and maintenance of synapses and regulation of synaptic plasticity. Genetic studies and biochemical analysis of the human brain tissue, cerebrospinal fluid, and sera from AD patients indicate that levels and function of synaptic cell adhesion molecules are affected in AD. Synaptic cell adhesion molecules interact with Aβ, a peptide accumulating in AD brains, which affects their expression and synaptic localization. Synaptic cell adhesion molecules also regulate the production of Aβ via interaction with the key enzymes involved in Aβ formation. Aβ-dependent changes in synaptic adhesion affect the function and integrity of synapses suggesting that alterations in synaptic adhesion play key roles in the disruption of neuronal networks in AD. PMID:27242933

  12. Preclinical Alzheimer disease-the challenges ahead.

    PubMed

    Sperling, Reisa A; Karlawish, Jason; Johnson, Keith A

    2013-01-01

    There is growing recognition that the pathophysiological process of Alzheimer disease (AD) begins many years prior to clinically obvious symptoms, and the concept of a presymptomatic or preclinical stage of AD is becoming more widely accepted. Advances in biomarker studies have enabled detection of AD pathology in vivo in clinically normal older individuals. The predictive value of these biomarkers at the individual patient level, however, remains to be elucidated. The ultimate goal of identifying individuals in the preclinical stages of AD is to facilitate early intervention to delay and perhaps even prevent emergence of the clinical syndrome. A number of challenges remain to be overcome before this concept can be validated and translated into clinical practice.

  13. Apraxia and Alzheimer's disease: review and perspectives.

    PubMed

    Lesourd, Mathieu; Le Gall, Didier; Baumard, Josselin; Croisile, Bernard; Jarry, Christophe; Osiurak, François

    2013-09-01

    Apraxia is one of the cognitive deficits that characterizes Alzheimer's disease. Despite its prevalence and relevance to diagnosing Alzheimer's disease, this topic has received little attention and is without comprehensive review. The review herein is aimed to fill this gap by first presenting an overview of the impairment caused in different clinical situations: pantomime of tool use, single tool use, real tool use, mechanical problem solving, function and manipulation knowledge tasks, and symbolic/meaningless gestures. On the basis of these results, we then propose alternative interpretations regarding the nature of the underlying mechanisms impaired by the disease. Also presented are principal methodological issues precluding firm conclusions from being drawn.

  14. Therapeutic potential of resveratrol in Alzheimer's disease.

    PubMed

    Vingtdeux, Valérie; Dreses-Werringloer, Ute; Zhao, Haitian; Davies, Peter; Marambaud, Philippe

    2008-12-03

    Several epidemiological studies indicate that moderate consumption of red wine is associated with a lower incidence of dementia and Alzheimer's disease. Red wine is enriched in antioxidant polyphenols with potential neuroprotective activities. Despite scepticism concerning the bioavailability of these polyphenols, in vivo data have clearly demonstrated the neuroprotective properties of the naturally occurring polyphenol resveratrol in rodent models for stress and diseases. Furthermore, recent work in cell cultures and animal models has shed light on the molecular mechanisms potentially involved in the beneficial effects of resveratrol intake against the neurodegenerative process in Alzheimer's disease.

  15. Evidence for major gene inheritance of Alzheimer disease in families of patients with and without Apolipoprotein E {epsilon}4

    SciTech Connect

    Rao, V.S.; Auerbach, S.A.; Farrer, L.A.

    1996-09-01

    Apolipoprotein E (APOE) genotype is the single most important determinant to the common form of Alzheimer disease (AD) yet identified. Several studies show that family history of AD is not entirely accounted for by APOE genotype. Also, there is evidence for an interaction between APOE genotype and gender. We carried out a complex segregation analysis in 636 nuclear families of consecutively ascertained and rigorously diagnosed probands in the Multi-Institutional Research in Alzheimer Genetic Epidemiology study in order to derive models of disease transmission which account for the influences of APOE genotype of the proband and gender. In the total group of families, models postulating sporadic occurrence, no major gene effect, random environmental transmission, and Mendelian inheritance were rejected. Transmission of AD in families of probands with at least one {epsilon}4 allele best fit a dominant model. Moreover, single gene inheritance best explained clustering of the disorder in families of probands lacking E4, but a more complex genetic model or multiple genetic models may ultimately account for risk in this group of families. Our results also suggest that susceptibility to AD differs between men and women regardless of the proband`s APOE status. Assuming a dominant model, AD appears to be completely penetrant in women, whereas only 62%-65% of men with predisposing genotypes develop AD. However, parameter estimates from the arbitrary major gene model suggests that AD is expressed dominantly in women and additively in men. These observations, taken together with epidemiologic data, are consistent with the hypothesis of an interaction between genes and other biological factors affecting disease susceptibility. 76 refs., 4 tabs.

  16. Failure of neuronal maturation in Alzheimer disease dentate gyrus.

    PubMed

    Li, Bin; Yamamori, Hidenaga; Tatebayashi, Yoshitaka; Shafit-Zagardo, Bridget; Tanimukai, Hitoshi; Chen, She; Iqbal, Khalid; Grundke-Iqbal, Inge

    2008-01-01

    The dentate gyrus, an important anatomic structure of the hippocampal formation, is one of the major areas in which neurogenesis takes place in the adult mammalian brain. Neurogenesis in the dentate gyrus is thought to play an important role in hippocampus-dependent learning and memory. Neurogenesis has been reported to be increased in the dentate gyrus of patients with Alzheimer disease, but it is not known whether the newly generated neurons differentiate into mature neurons. In this study, the expression of the mature neuronal marker high molecular weight microtubule-associated protein (MAP) isoforms MAP2a and b was found to be dramatically decreased in Alzheimer disease dentate gyrus, as determined by immunohistochemistry and in situ hybridization. The total MAP2, including expression of the immature neuronal marker, the MAP2c isoform, was less affected. These findings suggest that newly generated neurons in Alzheimer disease dentate gyrus do not become mature neurons, although neuroproliferation is increased.

  17. Increased cerebrospinal fluid pyruvate levels in Alzheimer's disease.

    PubMed

    Parnetti, L; Gaiti, A; Polidori, M C; Brunetti, M; Palumbo, B; Chionne, F; Cadini, D; Cecchetti, R; Senin, U

    1995-10-27

    Impaired energy metabolism is an early, predominant feature in Alzheimer's disease. In order to find out simple, reliable 'in vivo' markers for the clinical-biological typization of the disorder, we measured cerebrospinal fluid (CSF) glucose, lactate and pyruvate levels in patients suffering from dementia of Alzheimer type (DAT) and in healthy elderly controls. DAT group showed remarkably higher levels of pyruvate (P = 0.01), with no overlap with the values obtained in controls. CSF pyruvate levels were also significantly associated with the severity of dementia. Therefore, CSF pyruvate levels neatly separate DAT patients from controls, having also pathogenetic value.

  18. Knowledge of Natural Kinds in Semantic Dementia and Alzheimer's Disease

    ERIC Educational Resources Information Center

    Cross, Katy; Smith, Edward E.; Grossman, Murray

    2008-01-01

    We examined the semantic impairment for natural kinds in patients with probable Alzheimer's disease (AD) and semantic dementia (SD) using an inductive reasoning paradigm. To learn about the relationships between natural kind exemplars and how these are distinguished from manufactured artifacts, subjects judged the strength of arguments such as…

  19. Language Impairment in Alzheimer's Disease and Vascular Dementia.

    ERIC Educational Resources Information Center

    Lempinen, Maire; And Others

    A study of 21 patients with Alzheimer's Disease and 25 with vascular dementia, the two most common forms of dementia, investigated language impairments in the dementia syndrome to see if analysis of language disturbances is helpful in differential diagnosis. Diagnostic assessment included a neurological examination, detailed medical history,…

  20. Looking for Signs of Alzheimer's Disease

    ERIC Educational Resources Information Center

    Hodgson, Lynne Gershenson; Cutler, Stephen J.

    2003-01-01

    This study examined the correlates of symptom-seeking behavior for Alzheimer's disease (AD) among middle-aged persons. Symptom seeking, the tendency to search for signs of disease, is one manifestation of an individual's concern about developing AD. The data were obtained from a survey of two subsamples of 40-60 year old adults: 1) 108 adult…

  1. Progress Report on Alzheimer's Disease: Volume II.

    ERIC Educational Resources Information Center

    National Inst. on Aging (DHHS/PHS), Bethesda, MD.

    This document provides an overview of the state of scientific study of Alzheimer's disease, a disease of catastrophic proportions whose symptoms include serious forgetfulness; changes in personality; confused, restless, and irritable behavior; and problems with judgment, concentration, writing, reading, speech, and naming of objects. It discusses…

  2. Insights into Alzheimer disease pathogenesis from studies in transgenic animal models.

    PubMed

    Schaeffer, Evelin L; Figueiro, Micheli; Gattaz, Wagner F

    2011-01-01

    Alzheimer disease is the most common cause of dementia among the elderly, accounting for ~60-70% of all cases of dementia. The neuropathological hallmarks of Alzheimer disease are senile plaques (mainly containing p-amyloid peptide derived from amyloid precursor protein) and neurofibrillary tangles (containing hyperphosphorylated Tau protein), along with neuronal loss. At present there is no effective treatment for Alzheimer disease. Given the prevalence and poor prognosis of the disease, the development of animal models has been a research priority to understand pathogenic mechanisms and to test therapeutic strategies. Most cases of Alzheimer disease occur sporadically in people over 65 years old, and are not genetically inherited. Roughly 5% of patients with Alzheimer disease have familial Alzheimer disease--that is, related to a genetic predisposition, including mutations in the amyloid precursor protein, presenilin 1, and presenilin 2 genes. The discovery of genes for familial Alzheimer disease has allowed transgenic models to be generated through the overexpression of the amyloid precursor protein and/or presenilins harboring one or several mutations found in familial Alzheimer disease. Although none of these models fully replicates the human disease, they have provided valuable insights into disease mechanisms as well as opportunities to test therapeutic approaches. This review describes the main transgenic mouse models of Alzheimer disease which have been adopted in Alzheimer disease research, and discusses the insights into Alzheimer disease pathogenesis from studies in such models. In summary, the Alzheimer disease mouse models have been the key to understanding the roles of soluble b-amyloid oligomers in disease pathogenesis, as well as of the relationship between p-amyloid and Tau pathologies.

  3. Diagnostic Value of a Tablet-Based Drawing Task for Discrimination of Patients in the Early Course of Alzheimer's Disease from Healthy Individuals.

    PubMed

    Müller, Stephan; Preische, Oliver; Heymann, Petra; Elbing, Ulrich; Laske, Christoph

    2017-01-01

    There is a considerable delay in the diagnosis of dementia, which may reduce the effectiveness of available treatments. Thus, it is of great interest to develop fast and easy to perform, non-invasive and non-expensive diagnostic measures for the early detection of cognitive impairment and dementia. Here we investigate movement kinematics between 20 patients with early dementia due to Alzheimer's disease (eDAT), 30 patients with amnestic mild cognitive impairment (aMCI), and 20 cognitively healthy control (HC) individuals while copying a three-dimensional house using a digitizing tablet. Receiver-operating characteristic (ROC) curves and logistic regression analyzes have been conducted to explore whether alterations in movement kinematics could be used to discriminate patients with aMCI and eDAT from healthy individuals. Time-in-air (i.e., transitioning from one stroke to the next without touching the surface) differed significantly between patients with aMCI, eDAT, and HCs demonstrating an excellent sensitivity and a moderate specificity to discriminate aMCI subjects from normal elderly and an excellent sensitivity and specificity to discriminate patients affected by mild Alzheimer's disease from healthy individuals. Time-on-surface (i.e., time while stylus is touching the surface) differed only between HCs and patients with eDAT but not between HCs and patients with aMCI. Furthermore, total-time (i.e., time-in-air plus time-on-surface) did not differ between patients with aMCI and early dementia due to AD. Modern digitizing devices offer the opportunity to measure a broad range of visuoconstructive abilities that may be used as a fast and easy to perform screening instrument for the early detection of cognitive impairment and dementia in primary care.

  4. Feelings Without Memory in Alzheimer Disease

    PubMed Central

    Guzmán-Vélez, Edmarie; Feinstein, Justin S.

    2014-01-01

    Background: Patients with Alzheimer disease (AD) typically have impaired declarative memory as a result of hippocampal damage early in the disease. Far less is understood about AD’s effect on emotion. Objective: We investigated whether feelings of emotion can persist in patients with AD, even after their declarative memory for what caused the feelings has faded. Methods: A sample of 17 patients with probable AD and 17 healthy comparison participants (case-matched for age, sex, and education) underwent 2 separate emotion induction procedures in which they watched film clips intended to induce feelings of sadness or happiness. We collected real-time emotion ratings at baseline and at 3 post-induction time points, and we administered a test of declarative memory shortly after each induction. Results: As expected, the patients with AD had severely impaired declarative memory for both the sad and happy films. Despite their memory impairment, the patients continued to report elevated levels of sadness and happiness that persisted well beyond their memory for the films. This outcome was especially prominent after the sadness induction, with sustained elevations in sadness lasting for more than 30 minutes, even in patients with no conscious recollection for the films. Conclusions: These findings indicate that patients with AD can experience prolonged states of emotion that persist well beyond the patients’ memory for the events that originally caused the emotion. The preserved emotional life evident in patients with AD has important implications for their management and care, and highlights the need for caretakers to foster positive emotional experiences. PMID:25237742

  5. Quiz: Alzheimer's Disease | NIH MedlinePlus the Magazine

    MedlinePlus

    ... with mild Alzheimer's disease may be helped in day-to-day living by a list of daily plans notes ... help some people with mild Alzheimer's disease with day-to-day living. A big calendar, a list ...

  6. Neurogenesis and Alzheimer's disease: at the crossroads.

    PubMed

    Lazarov, Orly; Marr, Robert A

    2010-06-01

    While a massive and progressive neuronal loss in specific areas such as the hippocampus and cortex unequivocally underlies cognitive deterioration and memory loss in Alzheimer's disease, noteworthy alterations take place in the neurogenic microenvironments, namely, the subgranule layer of the dentate gyrus and the subventricular zone. Compromised neurogenesis presumably takes place earlier than onset of hallmark lesions or neuronal loss, and may play a role in the initiation and progression of neuropathology in Alzheimer's disease. Neurogenesis in the adult brain is thought to play a role in numerous forms and aspects of learning and memory and contribute to the plasticity of the hippocampus and olfactory system. Misregulated or impaired neurogenesis on the other hand, may compromise plasticity and neuronal function in these areas and exacerbate neuronal vulnerability. Interestingly, increasing evidence suggests that molecular players in Alzheimer's disease, including PS1, APP and its metabolites, play a role in adult neurogenesis. In addition, recent studies suggest that alterations in tau phosphorylation are pronounced in neurogenic areas, and may interfere with the potential central role of tau proteins in neuronal maturation and differentiation. On the other hand, numerous neurogenic players, such as Notch-1, ErbB4 and L1 are substrates of alpha- beta- and gamma- secretase that play a major role in Alzheimer's disease. This review will discuss current knowledge concerning alterations of neurogenesis in Alzheimer's disease with specific emphasis on the cross-talk between signaling molecules involved in both processes, and the ways by which familial Alzheimer's disease-linked dysfunction of these signaling molecules affect neurogenesis in the adult brain.

  7. A diagnostic approach in Alzheimer`s disease using three-dimensional stereotactic surface projections of Fluorine-18-FDG PET

    SciTech Connect

    Minoshima, S.; Frey, K.A.; Koeppe, R.A.

    1995-07-01

    To improve the diagnostic performance of PET as an aid in evaluating patients suspected of having Alzheimer`s disease, the authors developed a fully automated method which generates comprehensive image presentations and objective diagnostic indices. Fluorine-18-fluorodeoxyglucose PET image sets were collected from 37 patients with probable Alzheimer`s disease (including questionable and mild dementia), 22 normal subjects and 5 patients with cerebrovascular disease. Following stereotactic anatomic standardization, metabolic activity on an individual`s PET image set was extracted to a set of predefined surface pixels (three-dimensional stereotactic surface projection, 3D-SSP), which was used in the subsequent analysis. A normal database was created by averaging extracted datasets of the normal subjects. Patients` datasets were compared individually with the normal database by calculating a Z-score on a pixel-by-pixel basis and were displayed in 3D-SSP views for visual inspections. Diagnostic indices were then generated based on averaged Z-scores for the association cortices. Patterns and severities of metabolic reduction in patients with probable Alzheimer`s disease were seen in the standard 3D-SSP views of extracted raw data and statistical Z-scores. When discriminating patients with probable Alzheimer`s disease from normal subjects, diagnostic indices of the parietal association cortex and unilaterally averaged parietal-temporal-frontal cortex showed sensitivities of 95% and 97%, respectively, with a specificity of 100%. Neither index yielded false-positive results for cerebrovascular disease. 3D-SSP enables quantitative data extraction and reliable localization of metabolic abnormalities by means of stereotactic coordinates. The proposed method is a promising approach for interpreting functional brain PET scans. 45 refs., 5 figs.

  8. Alzheimer disease and cerebrovascular pathology: an update.

    PubMed

    Jellinger, K A

    2002-05-01

    Recent epidemiological and clinico-pathologic data suggest overlaps between Alzheimer disease (AD) and cerebrovascular lesions that may magnify the effect of mild AD pathology and promote progression of cognitive decline or even may precede neuronal damage and dementia. Vascular pathology in the aging brain and in AD includes: 1. cerebral amyloid angiopathy (CAA) with an incidence of 82-98% often associated with ApoE epsilon 2 and causing a) cerebral mass hemorrhages (around 70%, mainly in the frontal and parietal lobes), b) multiple or recurrent microhemorrhages (15%), and c) ischemic (micro-)infarcts or lacunes (around 20%). The frequency of these lesions increases with the severity of CAA and shows no correlation with that of senile amyloid plaques. CAA, significantly more frequent in patients with cerebral hemorrhages or infarcts than in aged controls, is an important risk factor for cerebrovascular lesions in AD. 2. Microvascular changes with decreased density and structural abnormalities causing regional metabolic and blood-brain barrier dysfunctions with ensuing neuronal damage. In large autopsy series of demented aged subjects, around 80% show Alzheimer type pathology, 20-40% with additional, often minor vascular lesions, 7-10% "pure" vascular dementia, and 3-5% "mixed" dementia (combination of AD and vascular encephalopathy). AD cases with additional minor cerebrovascular lesions have significantly more frequent histories of hypertension or infarcts than "pure" AD patients. Vascular lesions in AD include cortical microinfarcts, subcortical lacunes, white matter lesions / leukoencephalopathy, small hemorrhages and corticosubcortical infarcts, while in mixed type dementia multiple larger or hemispheral infarcts are more frequent. Small infarcts in AD patients have no essential impact on global cognitive decline which mainly depends on the severity of Alzheimer pathology, but in early stage of AD they may influence and promote the development of dementia

  9. Creativity and dementia: emerging diagnostic and treatment methods for Alzheimer's disease.

    PubMed

    Cummings, Jeffrey L; Miller, Bruce L; Christensen, Daniel D; Cherry, Debra

    2008-02-01

    Alzheimer's disease research is beginning to yield promising treatments and prevention strategies. Current Alzheimer's disease treatments benefit symptoms, but do not appreciably alter the basic disease process. The new generation of Alzheimer's disease medications, however, will likely include disease-modifying treatments, which will slow disease progression or stop it entirely. These new treatments pursue four points of intervention: increasing the clearance of amyloid-beta42 (Abeta42) proteins in the brain, blocking Abeta42 production, decreasing Abeta42 production, and decreasing Abeta42 aggregation. Neurogenerative therapies are being explored as well, suggesting future treatments may not only stop disease progression but also reverse it. Risk factors for developing Alzheimer's disease and factors associated with a lower risk of Alzheimer's disease have been identified. Future Alzheimer's disease management may come to resemble routine cardiovascular disease prevention and management, which involves the control of modifiable risk factors and the use of medications that decrease or stop underlying pathology. The hope is that such management will arrest the disease process before cognitive symptoms have begun. Like other neurologic illnesses, Alzheimer's disease has a profound impact on creativity. Alzheimer's disease attacks the right posterior part of the brain, which enables people to retrieve internal imagery and copy images. Alzheimer's disease patients may lose the ability to copy images entirely. However, people with Alzheimer's disease can continue to produce art by using their remaining strengths, such as color or composition instead of shapes or realism. Studying art and dementia is a model for identifying the strengths of psychiatric patients. Remarkably, art emerges in some patients even in the face of degenerative disease. In this expert roundtable supplement, Jeffrey L. Cummings, MD, offers an overview of recent advances in Alzheimer's disease

  10. Modifiable lifestyle risk factors for Alzheimer's disease.

    PubMed

    Flicker, Leon

    2010-01-01

    There is increasing evidence that some lifestyle factors are linked to the development of Alzheimer's disease. Many of these are potentially modifiable and include smoking, physical activity, education, social engagement, cognitive stimulation, and diet. Modification of most of these factors has other health advantages, increasing the potential benefits of modifying the individual's lifestyle. Unfortunately, most of the current evidence is based on observational data, and where human trials have been performed they have used surrogate outcomes rather than the development of Alzheimer's disease. For many of these modifiable lifestyle factors, such trials may never be performed, and an individual's choice may need to be based on the available evidence.

  11. Progenitor endothelial cell involvement in Alzheimer's disease

    SciTech Connect

    Budinger, Thomas F.

    2003-05-01

    There is compelling evidence that endothelial cells of the brain and periphery are dysfunctional in Alzheimer's Disease. There is evidence for a fundamental defect in, or abnormal aging of, endothelial progenitor cells in atherosclerosis. The possibility that endothelial cell defects are a primary cause for Alzheimer's Disease or other dementias can be researched by molecular and cell biology studies as well as cell trafficking studies using recently demonstrated molecular imaging methods. The evidence for abnormal endothelial function and the methods to explore this hypothesis are presented.

  12. [Prevention and treatment of Alzheimer disease].

    PubMed

    Donoso S, Archibaldo; Delgado D, Carolina

    2009-02-01

    The pharmacological interventions for Alzheimer disease should be based in its pathogenic mechanisms such as amyloidogenesis, tau hyperphosphorilation, disturbances in neurotransmission and changes in neuronal trophism. Other therapies derive from epidemiological observations, such as antioxidants and anti-inflammatory drugs, estrogens, statins and anti hypertensive drugs. Some life style interventions, such as changes in diet, exercise and brain stimulation could also be beneficial for the prevention of Alzheimer disease. Ongoing research on pathogenic mechanisms promises the discovery of more effective therapies. Healthy life style should always be recommended due to its benefit and lack of untoward effects.

  13. C-1073 (mifepristone) in the adjunctive treatment of Alzheimer's disease.

    PubMed

    DeBattista, Charles; Belanoff, Joseph

    2005-04-01

    Alzheimer's disease is frequently associated with abnormalities in the hypothalamic pituitary adrenal axis. Elevated cortisol levels in Alzheimer's disease may in turn be associated with a more rapid progression of the illness. In addition, elevated cortisol levels may directly contribute to cognitive deficits in Alzheimer's disease. Mifepristone is a potent antagonist of the glucocorticoid receptor and blocks the central actions of cortisol. The purpose of this study is to determine the effects of glucocorticoid receptor blockade with mifepristone on cognition in Alzheimer's disease.

  14. Providing quality palliative care in end-stage Alzheimer disease.

    PubMed

    Yeaman, Paul A; Ford, James L; Kim, Kye Y

    2013-08-01

    Providing quality palliative care is a daunting task profoundly impacted by diminished patient capacity at the end of life. Alzheimer disease (AD) is a disorder that erases our memories and is projected to increase dramatically for decades to come. By the time the patients with AD reach the end stage of the disease, the ability of patients to provide pertinent subjective complaints of pain and discomfort would have vanished. Historical perspectives of palliative care, exploration of the AD process, ethical issues, and crucial clinical considerations are provided to improve the understanding of disease progression and quality of care for patients with end-stage AD.

  15. The Effect of Reminiscence Therapy on Cognition, Depression, and Activities of Daily Living for Patients With Alzheimer Disease.

    PubMed

    Duru Aşiret, Güler; Kapucu, Sevgisun

    2016-01-01

    The purpose of this study was, conducted with experimental design, to investigate the effect of reminiscence therapy on cognition, depression, activities of daily living of institutionalized mild and moderate Alzheimer patients. The study was conducted with a total of 62 patients (31 intervention group and 31 control group) in four home care in Ankara, Turkey. Study was done between the July 1, 2013 and December 20, 2014. Reminiscence therapy sessions were held with groups consists of 4-5 patients, once a week with 30-35 minute duration for 12 weeks. Standardized Mini Mental Test was used in sample selection. Patients were listed through their mini mental test scores, and randomized as odd numbers to control group and even numbers to intervention group. Data were collected with forms developed by researcher 'Data Sheet' and 'Activities of Daily Living Follow-up Form' as well as scales 'Standardized Mini Mental Test' and 'Geriatric Depression Scale'. Chi-square, Mann Whitney-U test, variance analyses in repeated measures and Bonferroni tests were used for analysis. The increase in mean Standardized Mini Mental Test score and the decrease in mean Geriatric Depression Scale score of the individuals in the intervention group compared to the control group at the end of the reminiscence therapy was statistically significant (P < 0.05). At the end of reminiscence therapy sessions, increase in cognition and decrease in depression were found statistically significant in intervention group.

  16. 76 FR 68615 - National Alzheimer's Disease Awareness Month, 2011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ... eliminate Alzheimer's disease. Research funded by the National Institutes of Health has identified genetic... Documents#0;#0; ] Proclamation 8745 of November 1, 2011 National Alzheimer's Disease Awareness Month, 2011... heartbreak of watching a loved one struggle with Alzheimer's disease is a pain they know all too...

  17. Intrathecal inflammation precedes development of Alzheimer's disease

    PubMed Central

    Tarkowski, E; Andreasen, N; Tarkowski, A; Blennow, K

    2003-01-01

    Objectives: To analyse the cerebrospinal fluid (CSF) values of the proinflammatory cytokines, interleukin 1ß (IL1ß), tumour necrosis factor α (TNFα), GM-CSF, of the anti-inflammatory cytokine TGFß, of tau protein, a marker for neurodegeneration, and of ß amyloid (Aß), a protein involved in the formation of senile plaques, in prospectively followed up patients with mild cognitive impairment (MCI). Methods: Analyses of CSF levels of TNFα, IL1ß, GM-CSF, TGFß, ßa, and tau protein were performed using ELISA in 56 patients with MCI who were followed up prospectively and in 25 age matched, healthy controls. Results: Patients with MCI displayed significantly higher levels of TNFα and tau protein and significantly lower levels of TGFß and Aß compared with the healthy controls. After nine months of follow up, 25 patients still displayed MCI while the remaining 31 patients had progressed to Alzheimer's disease (AD). Only MCI patients who progressed to AD at follow up, showed significantly higher CSF levels of TNFα than controls. In addition, reduced CSF-Aß42 levels were only found in MCI patients that progressed to AD, further supporting the notion that disturbed metabolism of Aß is an early finding in AD. Conclusions: These results demonstrate increased production of the proinflammatory cytokine, TNFα and decreased production of the anti-inflammatory cytokine TGFß in patients with MCI at risk to develop AD, suggesting a propensity towards inflammation in this patient group and indicating that CNS inflammation is a early hallmark in the pathogenesis of AD. PMID:12933918

  18. International Work Group criteria for the diagnosis of Alzheimer disease.

    PubMed

    Cummings, Jeffrey L; Dubois, Bruno; Molinuevo, José L; Scheltens, Philip

    2013-05-01

    Alzheimer-type biomarker changes are identifiable in asymptomatic and mildly symptomatic predementia phases of Alzheimer disease (AD) and AD dementia. The International Work Group (IWG) guidelines for diagnosis identify a unified spectrum of 3 phases. The classic clinical feature that indicates AD is an episodic memory defect of the amnestic type. IWG criteria require biomarker support for the diagnoses of AD at any clinical stage. Pathophysiologic and topographic biomarkers are recognized. These criteria are proposed to allow highly specific diagnosis of AD and assist in identifying patients for clinical trials of AD-related treatments and other types of AD research.

  19. [Alzheimer's disease with secondary Parkinson's syndrome. Case report of a patient with dementia and Parkinson's syndrome after long-term occupational exposure to insecticides, herbicides, and pesticides].

    PubMed

    Laske, C; Wormstall, H; Einsiedler, K; Buchkremer, G

    2004-11-01

    This case report describes long-term occupational exposure to agricultural insecticides, herbicides, and pesticides as possible environmental risk factors of Alzheimer's disease (AD) and Parkinson's syndrome in a 59-year-old man. Initially the patient complained about disturbances in concentration, mnestic deficits, and problems finding words. In the further course of the disease, he developed Parkinson's syndrome with predominant hypokinesia and rigor in addition to mild-to-moderate dementia. Low levels of beta-amyloid 1-42 were found in the CSF. Electroencephalography showed left frontotemporal theta waves. Cranial MRI revealed general brain atrophy with a maximum biparietally. In cerebral positron emission tomography, general hypometabolism was found with maxima biparietally and left frontally. The possible differential diagnosis of AD and Parkinson's syndrome is discussed.

  20. beta. amyloid gene duplication in Alzheimer's disease and karyotypically normal Down syndrome

    SciTech Connect

    Delabar, J.; Goldgaber, D.; Lamour, Y.; Nicole, A.; Huret, J.; De Groucy, J.; Brown, P.; Gajdusek, D.C.; Sinet, P.

    1987-03-13

    With the recently cloned complementary DNA probe, lambdaAm4 for the chromosome 21 gene encoding brain amyloid polypeptide (..beta.. amyloid protein) of Alzheimer's disease, leukocyte DNA from three patients with sporadic Alzheimer's disease and two patients with karyotypically normal Down syndrome was found to contain three copies of this bene. Because a small region of chromosome 21 containing the ets-2 gene is duplicated in patients with Alzheimer's disease, as well as in karyotypically normal Down syndrome, duplication of a subsection of the critical segment of chromosome 21 that is duplicated in Down syndrome may be the genetic defect in Alzeimer's disease.

  1. Alzheimer's disease: analyzing the missing heritability.

    PubMed

    Ridge, Perry G; Mukherjee, Shubhabrata; Crane, Paul K; Kauwe, John S K

    2013-01-01

    Alzheimer's disease (AD) is a complex disorder influenced by environmental and genetic factors. Recent work has identified 11 AD markers in 10 loci. We used Genome-wide Complex Trait Analysis to analyze >2 million SNPs for 10,922 individuals from the Alzheimer's Disease Genetics Consortium to assess the phenotypic variance explained first by known late-onset AD loci, and then by all SNPs in the Alzheimer's Disease Genetics Consortium dataset. In all, 33% of total phenotypic variance is explained by all common SNPs. APOE alone explained 6% and other known markers 2%, meaning more than 25% of phenotypic variance remains unexplained by known markers, but is tagged by common SNPs included on genotyping arrays or imputed with HapMap genotypes. Novel AD markers that explain large amounts of phenotypic variance are likely to be rare and unidentifiable using genome-wide association studies. Based on our findings and the current direction of human genetics research, we suggest specific study designs for future studies to identify the remaining heritability of Alzheimer's disease.

  2. Infection, systemic inflammation, and Alzheimer's disease.

    PubMed

    Lim, Siok Lam; Rodriguez-Ortiz, Carlos J; Kitazawa, Masashi

    2015-08-01

    Alzheimer's disease (AD) is a leading cause of dementia among elderly. Yet, its etiology remains largely unclear. In this review, we summarize studies that associate systemic infection and neuroinflammation with AD, while highlighting that early-life or life-long exposure to infectious agents predisposes one to develop AD at a later age.

  3. Famous forgetters: notable people and Alzheimer's disease.

    PubMed

    Jones, Jeffrey M; Jones, Joni L

    2010-03-01

    As life expectancy continues to increase, Alzheimer's disease (AD) has become much more prevalent and as yet there is no cure. This has given rise to the situation Tithonus faced in Greek mythology of living longer but not staying young. In this article, the authors explore this phenomenon while reviewing some notable people and AD.

  4. Vascular and metabolic reserve in Alzheimer's disease.

    PubMed

    Nagata, K; Kondoh, Y; Atchison, R; Sato, M; Satoh, Y; Watahiki, Y; Hirata, Y; Yokoyama, E

    2000-01-01

    Vascular and metabolic reserve were analyzed in probable Alzheimer's disease (AD) and vascular dementia (VaD). Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF) were measured quantitatively with positron emission tomography (PET). Vascular reactivity (VR) was also calculated by comparing the CBF during 5% CO(2) inhalation with the CBF during normal breathing. Vascular transit time (VTT) that was calculated as a ratio of CBV/CBF and VR reflect vasodilating capacity of the small resistance vessels, whereas OEF designates metabolic (oxygen-extraction) reserve in threatening brain ischemia. Significant increase in OEF was seen in the parieto-temporal cortex and both VTT and VR were preserved in AD patients. By constrast, there was no significant increase in OEF whereas VTT was prolonged and VR was markedly depressed in VaD patients. The increase of OEF and preserved VTT and VR seen in AD patients indicate the possible participation of vascular factors in the pathogenesis of AD perhaps at the capillary level.

  5. Why do we get Alzheimer's disease?

    SciTech Connect

    Wyss-Coray, Tony

    2006-10-02

    Neurodegenerative diseases and Alzheimer's disease (AD) in particular, are among the major health concerns of the elderly in industrialized societies. The cause of AD is unknown and no disease-modifying treatments are available. The disease is characterized clinically by a progressive dementia and pathologically by the accumulation of protein aggregates in the brain and a profound loss of nerve cells. It has also become clear recently that local immune responses are activated in the AD brain and may have a role in the disease. Our laboratory uses genetic mouse models to understand the disease process and to identify potential therapeutic targets.

  6. Why Do We Get Alzheimer's Disease?

    SciTech Connect

    Wyss-Coray, Tony

    2006-01-02

    Neurodegenerative diseases and Alzheimer's disease (AD) in particular, are among the major health concerns of the elderly in industrialized societies. The cause of AD is unknown and no disease-modifying treatments are available. The disease is characterized clinically by a progressive dementia and pathologically by the accumulation of protein aggregates in the brain and a profound loss of nerve cells. It has also become clear recently that local immune responses are activated in the AD brain and may have a role in the disease. Our laboratory uses genetic mouse models to understand the disease process and to identify potential therapeutic targets.

  7. Gene Therapy Strategies for Alzheimer's Disease: An Overview.

    PubMed

    Alves, Sandro; Fol, Romain; Cartier, Nathalie

    2016-02-01

    Key neuropathological hallmarks of Alzheimer's disease (AD) are extracellular amyloid plaques and intracellular accumulation of hyperphosphorylated Tau protein. The mechanisms underlying these neuropathological changes remain unclear. So far, research on AD therapy has had limited success in terms of symptomatic treatments although it has also had several failures for disease-modifying drugs. Gene transfer strategies to the brain have contributed to evaluate in animal models many interesting tracks, some of which should deserve clinical applications in AD patients in the future.

  8. The importance of being apt: metaphor comprehension in Alzheimer's disease

    PubMed Central

    Roncero, Carlos; de Almeida, Roberto G.

    2014-01-01

    We investigated the effect of aptness in the comprehension of copular metaphors (e.g., Lawyers are sharks) by Alzheimer's Disease (AD) patients. Aptness is the extent to which the vehicle (e.g., shark) captures salient properties of the topic (e.g., lawyers). A group of AD patients provided interpretations for metaphors that varied both in aptness and familiarity. Compared to healthy controls, AD patients produced worse interpretations, but interpretation ability was related to a metaphor's aptness rather than to its familiarity level, and patients with superior abstraction ability produced better interpretations. Therefore, the ability to construct figurative interpretations for metaphors is not always diminished in AD patients nor is it dependent only on the novelty level of the expression. We show that Alzheimer's patients' capacity to build figurative interpretations for metaphors is related to both item variables, such as aptness, and participant variables, such as abstraction ability. PMID:25520642

  9. Potential therapeutic system for Alzheimer's disease: removal of blood Aβs by hemodialzyers and its effect on the cognitive functions of renal-failure patients.

    PubMed

    Kato, Masao; Kawaguchi, Kazunori; Nakai, Sigeru; Murakami, Kazutaka; Hori, Hideo; Ohashi, Atsushi; Hiki, Yoshiyuki; Ito, Shinji; Shimano, Yasunobu; Suzuki, Nobuo; Sugiyama, Satoshi; Ogawa, Hiroshi; Kusimoto, Hiroko; Mutoh, Tatsuro; Yuzawa, Yukio; Kitaguchi, Nobuya

    2012-12-01

    The pathological changes of Alzheimer's disease include the deposition of amyloid β protein (Aβ) as senile plaques in the brain. We hypothesized that the rapid removal of Aβs from the blood may act as a peripheral Aβ drainage sink from the brain. In this study, the plasma Aβ concentrations and the cognitive functions were investigated for in 57 patients on hemodailysis (69.4 ± 3.8 years), 26 renal-failure patients without hemodialysis (66.6 ± 14.7 years), and 17 age-matched healthy controls (66.6 ± 4.1 years). The concentrations of plasma Aβs increased along with the decline of renal functions. Moreover, the renal-failure patients without hemodialysis and with poorer renal functions showed lower cognitive functions. The plasma concentrations of Aβ(1-42) correlated with serum creatinine (P < 0.001) and Mini-Mental-State Examination scores (P = 0.017). The dialyzers effectively removed Aβs in the blood during hemodialysis sessions. The plasma Aβ concentrations showed steady or slightly decreasing along with duration of hemodialysis. The total amount of Aβs removed during a hemodialysis session was calculated to be comparable to the Aβs dissolved in the blood and the cerebrospinal fluid. The MMSE scores of the hemodialysis patients showed no clear decrease in longer hemodialysis duration. Therefore, the therapeutic approach for Alzheimer's disease by removing Aβs from the blood is worthy of further investigation, including whether or not Aβs in the brain decrease.

  10. Genetic defect causing familial Alzheimer's disease maps on chromosome 21

    SciTech Connect

    St. George-Hyslop, P.H.; Tanzi, R.E.; Polinsky, R.J.; Haines, J.L.; Nee, L.; Watkins, P.C.; Myers, R.H.; Feldman, R.G.; Pollen, D.; Drachman, D.; Growdon, J.

    1987-02-20

    Alzheimer's disease is a leading cause of morbidity and mortality among the elderly. Several families have been described in which Alzheimer's disease is caused by an autosomal dominant gene defect. The chromosomal location of this defective gene has been discovered by using genetic linkage to DNA markers on chromosome 21. The localization on chromosome 21 provides an explanation for the occurrence of Alzheimer's disease-like pathology in Down syndrome. Isolation and characterization of the gene at this locus may yield new insights into the nature of the defect causing familial Alzheimer's disease and possibly, into the etiology of all forms of Alzheimer's disease.

  11. Natural antioxidants protect neurons in Alzheimer's disease and Parkinson's disease.

    PubMed

    Zhao, Baolu

    2009-04-01

    "Modern" medicine and pharmacology require an effective medical drug with a single compound for a specific disease. This seams very scientific but usually has unavoidable side effects. For example, the chemical therapy to cancer can totally damage the immunological ability of the patient leading to death early than non-treatment. On the other hand, natural antioxidant drugs not only can cure the disease but also can enhance the immunological ability of the patient leading to healthier though they usually have several compounds or a mixture. For the degenerative disease such as Alzheimer's disease (AD) and Parkinson's disease (PD), natural antioxidant drugs are suitable drugs, because the pathogenesis of these diseases is complex with many targets and pathways. These effects are more evidence when the clinic trial is for long term treatment. The author reviews the studies on the protecting effects of natural antioxidants on neurons in neurodegenerative diseases, especially summarized the results about protective effect of green tea polyphenols on neurons against apoptosis of cellular and animal PD models, and of genestine and nicotine on neurons against A beta-induced apoptosis of hippocampal neuronal and transgenic mouse AD models.

  12. Diagnosis of Alzheimer's disease and multiple infarct dementia by tomographic imaging of iodine-123 IMP

    SciTech Connect

    Cohen, M.B.; Graham, L.S.; Lake, R.; Metter, E.J.; Fitten, J.; Kulkarni, M.K.; Sevrin, R.; Yamada, L.; Chang, C.C.; Woodruff, N.

    1986-06-01

    Tomographic imaging of the brain was performed using a rotating slant hole collimator and (/sup 123/I)N-isopropyl p-iodoamphetamine (IMP) in normal subjects (n = 6) and patients with either Alzheimer's disease (n = 5) or multiple infarct dementia (n = 3). Four blinded observers were asked to make a diagnosis from the images. Normal subjects and patients with multiple infarct dementia were correctly identified. Alzheimer's disease was diagnosed in three of the five patients with this disease. One patient with early Alzheimer's disease was classified as normal by two of the four observers. Another patient with Alzheimer's disease had an asymmetric distribution of IMP and was incorrectly diagnosed as multiple infarct dementia by all four observers. Limited angle tomography of the cerebral distribution of /sup 123/I appears to be a useful technique for the evaluation of demented patients.

  13. Progressive biparietal atrophy: an atypical presentation of Alzheimer's disease.

    PubMed Central

    Ross, S J; Graham, N; Stuart-Green, L; Prins, M; Xuereb, J; Patterson, K; Hodges, J R

    1996-01-01

    OBJECTIVES: To define the clinical, neuropsychological, and radiological features of bilateral parietal lobe atrophy. METHODS: Four patients underwent a comprehensive longitudinal neuropsychological assessment, as well as MRI and HMPAO-SPECT. RESULTS: The consistent findings in the patients were early visuospatial problems, agraphia of a predominantly peripheral (or apraxic) type, and difficulty with bimanual tasks, all of which outweighted deficits in memory and language until later in the course of the illness. As the disease progressed, impairments in the phonological aspects of language and in auditory-verbal short term memory were often striking, perhaps reflecting spread from the parietal lobe to perisylvian language areas. Three patients went on to develop a global dementia and fulfilled the criteria for a clinical diagnosis of probable Alzheimer's disease; the fourth patient has only recently been identified. Neuroimaging disclosed bilateral parietal lobe atrophy (MRI) and hypoperfusion (SPECT), which was out of proportion to that seen elsewhere in the brain. One patient has died and had pathologically confirmed Alzheimer's disease with particular concentration in both superior parietal lobes. CONCLUSIONS: Bilateral biparietal atrophy is a recognisable clinical syndrome which can be the presenting feature of Alzheimer's disease. Although the label "posterior cortical atrophy" has been applied to such cases, review of the medical literature suggests that this broad rubric actually consists of two main clinical syndromes with features reflecting involvement of the occipitotemporal (ventral) and biparietal (dorsal) cortical areas respectively. Images PMID:8890778

  14. Immunolocalization of Kisspeptin Associated with Amyloid-β Deposits in the Pons of an Alzheimer's Disease Patient

    PubMed Central

    Ashioti, Maria; Nercessian, Amanda N.; Milton, Nathaniel G. N.

    2013-01-01

    The pons region of the Alzheimer's disease (AD) brain is one of the last to show amyloid-β (Aβ) deposits and has been suggested to contain neuroprotective compounds. Kisspeptin (KP) is a hormone that activates the hypothalamic-pituitary-gonadal axis and has been suggested to be neuroprotective against Aβ toxicity. The localization of KP, plus the established endogenous neuroprotective compounds corticotropin releasing hormone (CRH) and catalase, in tissue sections from the pons region of a male AD subject has been determined in relation to Aβ deposits. Results showed Aβ deposits also stained with KP, CRH, and catalase antibodies. At high magnification the staining of deposits was either KP or catalase positive, and there was only a limited area of the deposits with KP-catalase colocalization. The CRH does not bind Aβ, whilst both KP and catalase can bind Aβ, suggesting that colocalization in Aβ deposits is not restricted to compounds that directly bind Aβ. The neuroprotective actions of KP, CRH, and catalase were confirmed in vitro, and fibrillar Aβ preparations were shown to stimulate the release of KP in vitro. In conclusion, neuroprotective KP, CRH, and catalase all colocalize with Aβ plaque-like deposits in the pons region from a male AD subject. PMID:26317001

  15. Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer's disease.

    PubMed

    Ho Kim, Jae; Franck, Julien; Kang, Taewook; Heinsen, Helmut; Ravid, Rivka; Ferrer, Isidro; Hee Cheon, Mi; Lee, Joo-Yong; Shin Yoo, Jong; Steinbusch, Harry W; Salzet, Michel; Fournier, Isabelle; Mok Park, Young

    2015-06-10

    Alzheimer's disease (AD) is the most common form of dementia; however, mechanisms and biomarkers remain unclear. Here, we examined hippocampal CA4 and dentate gyrus subfields, which are less studied in the context of AD pathology, in post-mortem AD and control tissue to identify possible biomarkers. We performed mass spectrometry-based proteomic analysis combined with label-free quantification for identification of differentially expressed proteins. We identified 4,328 proteins, of which 113 showed more than 2-fold higher or lower expression in AD hippocampi than in control tissues. Five proteins were identified as putative AD biomarkers (MDH2, PCLO, TRRAP, YWHAZ, and MUC19 isoform 5) and were cross-validated by immunoblotting, selected reaction monitoring, and MALDI imaging. We also used a bioinformatics approach to examine upstream signalling interactions of the 113 regulated proteins. Five upstream signalling (IGF1, BDNF, ZAP70, MYC, and cyclosporin A) factors showed novel interactions in AD hippocampi. Taken together, these results demonstrate a novel platform that may provide new strategies for the early detection of AD and thus its diagnosis.

  16. Education and occupation provide reserve in both ApoE ε4 carrier and noncarrier patients with probable Alzheimer's disease.

    PubMed

    Garibotto, V; Borroni, B; Sorbi, S; Cappa, S F; Padovani, A; Perani, D

    2012-10-01

    According to the reserve hypothesis, a high educational/occupational attainment can modulate Alzheimer's disease (AD) clinical expression. The impact of the Apolipoprotein E (ApoE) ε4 allele on the reserve mechanism in AD has not been assessed. Aim of this European multicenter study was to evaluate the metabolic correlates of reserve and ApoE genotype in early probable AD. 51 AD subjects, 27 ε4 carriers, and 24 noncarriers, underwent FDG-PET brain imaging. We used the general linear model as implemented in SPM2 to test for the linear correlation of a reserve index, accounting for both educational and occupational level, with brain glucose metabolism, controlling for demographic variables (age and gender) and for cognitive performance. We found an inverse correlation between a reserve index, accounting for educational/occupational level, and metabolism in the posterior cingulate cortex and precuneus in both ε4 carriers and noncarriers, and no significant difference between the groups. We show that education and occupation act as proxies for reserve in ε4 carriers, compensating for an unfavorable genetic background; we also show that the degree of compensation does not differ significantly by ApoE ε4 status.

  17. The role of adenosine in Alzheimer's disease.

    PubMed

    Rahman, Anisur

    2009-09-01

    Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system manifested by cognitive and memory deterioration, a variety of neuropsychiatric symptoms, behavioral disturbances, and progressive impairment of daily life activities. Current pharmacotherapies are restricted to symptomatic interventions but do not prevent progressive neuronal degeneration. Therefore, new therapeutic strategies are needed to intervene with these progressive pathological processes. In the past several years adenosine, a ubiquitously released purine ribonucleoside, has become important for its neuromodulating capability and its emerging positive experimental effects in neurodegenerative diseases. Recent research suggests that adenosine receptors play important roles in the modulation of cognitive function. The present paper attempts to review published reports and data from different studies showing the evidence of a relationship between adenosinergic function and AD-related cognitive deficits. Epidemiological studies have found an association between coffee (a nonselective adenosine receptor antagonist) consumption and improved cognitive function in AD patients and in the elderly. Long-term administration of caffeine in transgenic animal models showed a reduced amyloid burden in brain with better cognitive performance. Antagonists of adenosine A2A receptors mimic these beneficial effects of caffeine on cognitive function. Neuronal cell cultures with amyloid beta in the presence of an A2A receptor antagonist completely prevented amyloid beta-induced neurotoxicity. These findings suggest that the adenosinergic system constitutes a new therapeutic target for AD, and caffeine and A2A receptor antagonists may have promise to manage cognitive dysfunction in AD.

  18. The approach and management of bruxism in Alzheimer's disease: An under-recognized habit that concerns caregivers (innovative practice).

    PubMed

    Mathew, Thomas; Venkatesh, Shruthi; Srinivas, Meghana

    2017-01-01

    Bruxism (teeth grinding) is an under-recognized cause of caregiver concern in patients with Alzheimer's disease. We report two cases of Alzheimer's disease with bruxism that caused significant distress to the caregivers. Patient data were collected from the case records of our hospital. One patient presented with early Alzheimer's disease and another with advanced Alzheimer's disease had bruxism causing significant caregiver distress. One patient was treated with botulinum toxin type A with complete relief of the symptom. Bruxism in Alzheimer's disease patients can be a cause of caregiver distress. It can be successfully treated with botulinum toxin. Whether bruxism is rare in Alzheimer's disease or is under-reported is to be evaluated in future studies.

  19. How Can Music Help People Who Have Alzheimer's Disease?

    MedlinePlus

    Music and Alzheimer's: Can it help? How can music help people who have Alzheimer's disease? Answers from ... D. Research suggests that listening to or singing music can provide emotional and behavioral benefits for people ...

  20. Peripheral markers of Alzheimer's disease: surveillance of white blood cells.

    PubMed

    Shad, Kaneez Fatima; Aghazadeh, Yashar; Ahmad, Sagheer; Kress, Bodo

    2013-08-01

    Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. This is a mechanism of innate immunity, which may cause an increase in the number of monocytes and neutrophils circulating in the blood. Literature indicated that chronic inflammation might be a factor in developing neurological problems, including Alzheimer's, Parkinson's and other similar illnesses. Our main objective is to identify peripheral markers of Alzheimer's disease and for that purpose; we are looking at the profile of white blood cells focusing on monocytes, neutrophils, lymphocytes and basophils. Twenty-seven patients of Alzheimer's disease (AD), diagnosed by magnetic resonance imaging and neuropsychological tests were observed for their blood profile. Key observations during this study were that the levels of monocytes in the blood of the diagnosed AD patients were high irrespective of their age and sex. For those patients whose monocytes were in normal range their neutrophil levels were significantly high. Whereas blood levels of lymphocytes and basophils were found to be constantly low. Escalated levels of monocytes and neutrophils are hallmarks of chronic inflammation and may be precursor to Alzheimer's disease. A low lymphocyte count specifies that the body's resistance to fight infection is substantially reduced, whereas low basophil levels indicates their over utilization due to chronic allergic inflammatory condition. Future studies involved closer look at the cytokines produced by these white blood cells especially TNF IL-1, and IL-12, which are products of monocytes. Likewise, blood glucose and creatinine levels were high whereas calcium ions were low. Our studies indicated that white blood cells along with other inflammatory byproducts may act as peripheral markers for early diagnosis of Alzheimer's disease.

  1. Anatomically constrained region deformation for the automated segmentation of the hippocampus and the amygdala: Method and validation on controls and patients with Alzheimer's disease.

    PubMed

    Chupin, Marie; Mukuna-Bantumbakulu, A Romain; Hasboun, Dominique; Bardinet, Eric; Baillet, Sylvain; Kinkingnéhun, Serge; Lemieux, Louis; Dubois, Bruno; Garnero, Line

    2007-02-01

    We describe a new algorithm for the automated segmentation of the hippocampus (Hc) and the amygdala (Am) in clinical Magnetic Resonance Imaging (MRI) scans. Based on homotopically deforming regions, our iterative approach allows the simultaneous extraction of both structures, by means of dual competitive growth. One of the most original features of our approach is the deformation constraint based on prior knowledge of anatomical features that are automatically retrieved from the MRI data. The only manual intervention consists of the definition of a bounding box and positioning of two seeds; total execution time for the two structures is between 5 and 7 min including initialisation. The method is evaluated on 16 young healthy subjects and 8 patients with Alzheimer's disease (AD) for whom the atrophy ranged from limited to severe. Three aspects of the performances are characterised for validating the method: accuracy (automated vs. manual segmentations), reproducibility of the automated segmentation and reproducibility of the manual segmentation. For 16 young healthy subjects, accuracy is characterised by mean relative volume error/overlap/maximal boundary distance of 7%/84%/4.5 mm for Hc and 12%/81%/3.9 mm for Am; for 8 Alzheimer's disease patients, it is 9%/84%/6.5 mm for Hc and 15%/76%/4.5 mm for Am. We conclude that the performance of this new approach in data from healthy and diseased subjects in terms of segmentation quality, reproducibility and time efficiency compares favourably with that of previously published manual and automated segmentation methods. The proposed approach provides a new framework for further developments in quantitative analyses of the pathological hippocampus and amygdala in MRI scans.

  2. [Car driving, cognitive aging and Alzheimer disease].

    PubMed

    Fabrigoule, Colette; Lafont, Sylviane

    2015-10-01

    Older drivers are more numerous on the roads. They are expert drivers, but with increasing age certain physiological changes can interfere with driving, which is a complex activity of daily living. Older drivers are involved in fewer accidents than younger drivers, but they have a higher accident rate per kilometer driven. The elderly are heavily represented in the balance sheet of road deaths, being motorists or pedestrians. This high mortality is largely explained by their physical frailty. In the presence of deficits, self-regulation of driving habits, changes/reductions or stopping in driving activity occur in the elderly. But cognitive deficits are associated with an increased risk of accidents. Among drivers with Alzheimer's disease, there is a heterogeneity of driving ability, making difficult the advisory role of a physician for driving. A protocol for physicians was developed to assess cognitive impairments that may affect driving in an elderly patient. The car plays an important role in the autonomy of the elderly and patient advice on stopping driving should take into account the risk/benefit ratio.

  3. Role of thiamine in Alzheimer's disease.

    PubMed

    Lu'o'ng, Khanh vinh quoc; Nguyen, Lan Thi Hoang

    2011-12-01

    Alzheimer's disease (AD) is the most common form of dementia in elderly individuals and is associated with progressive neurodegeneration of the human neocortex. Thiamine levels and the activity of thiamine-dependent enzymes are reduced in the brains and peripheral tissues of patients with AD. Genetic studies have provided the opportunity to determine what proteins link thiamine to AD pathology (ie, transketolase, apolipoprotein E, α-1-antitrypsin, pyruvate dehydrogenase complex, p53, glycogen synthetase kinase-3β, c-Fos gene, the Sp1 promoter gene, and the poly(ADP-ribosyl) polymerase-1 gene). We reviewed the association between histopathogenesis and neurotransmitters to understand the relationship between thiamine and AD pathology. Oral thiamine trials have been shown to improve the cognitive function of patients with AD; however, absorption of thiamine is poor in elderly individuals. In the early stage of thiamine-deficient encephalopathy (Wernicke's encephalopathy), however, parental thiamine has been used successfully. Therefore, further studies are needed to determine the benefits of using parental thiamine as a treatment for AD.

  4. [Treatment of neuropsychiatric symptoms in Alzheimer's disease].

    PubMed

    Kaufer, D

    The overall goal of all therapeutic interventions in Alzheimer s disease (AD) is the optimisation of the adaptive functions and quality of life of these patients. The general strategy for the use of pharmacological interventions in the treatment of neuropsychiatric manifestations of AD includes the following: 1) An exhaustive evaluation of the psychiatric symptomatology; 2) Establish a hierachy of the simptoms to treat based on their severity of symptoms and on their impact on the caregiver; 3) The identification of an adequate agent based on the type of symptoms and subject s characteristics; 4) The initial use of low doses with gradual titration, and 5) Changing one drug at a time. Regarding psychotic symptons, the introduction of new agents (e.g., risperidone) has replaced the use of traditional treatments (e.g., thioridazine) in patients with AD. The presence of psychomotor agitation and aggression can be treated with great variety of drugs, such as antipsychotics, anticonvulsants, antidepressants, and sedatives. Selective serotonine re uptake inhibitors are the treatment of choice for depressive symptomatology. The cholinesterase inhibitors have shown to be useful in the treatment of hallucinations, anxiety and apathy.

  5. Alternative Abeta immunotherapy approaches for Alzheimer's disease.

    PubMed

    Town, Terrence

    2009-04-01

    In a seminal report in 1999, Schenk and colleagues demonstrated that vaccination of a mouse model of Alzheimer's disease (AD) with amyloid-beta(1-42) peptide (Abeta(1-42)) and adjuvant resulted in striking mitigation of AD-like pathology - giving rise to the field of AD immunotherapy. Later studies confirmed this result in other mouse models of AD and additionally showed cognitive improvement after Abeta vaccination. Based on these results, early developmental clinical trials ensued to immunize AD patients with Abeta(1-42) plus adjuvant (so-called "active" Abeta immunotherapy; trade name AN-1792; Elan Pharmaceuticals, Dublin, Ireland). However, the phase IIa trial was halted after 6 % of patients developed aseptic meningoencephalitis. Despite occurrence of this adverse event, many individuals demonstrated high serum antibody titres to Abeta and histological evidence of clearance of the hallmark AD pathology, beta-amyloid plaques. While raising justifiable safety concerns, these important results nonetheless demonstrated the feasibility of the active Abeta immunotherapy approach. This review focuses on alternative approaches to active Abeta vaccination that are currently in various stages of development - from pre-clinical studies in animal models to current clinical trials. Specifically, the focus is on those strategies that target inflammatory and immune aspects of AD, and can therefore be classified as immunotherapeutic in a broad sense.

  6. [Alzheimer disease--contribution of renin-angiotensin system to Alzheimer disease progression].

    PubMed

    Ohrui, Takashi

    2012-09-01

    There is increasing evidence that certain components of the renin-angiotensin system (RAS) may have a crucial role in learning and memory processes. We have previously shown that brain-penetrating ACE inhibitors can reduce the incidence of Alzheimer diseases (AD) in elderly hypertensive patients and that hypertension treatment with brain penetrating ACE inhibitors slowed the rate of cognitive decline in mild-to-moderate AD patients with hypertension. We speculate that the favorable effects might be due to the direct effects of brain-penetrating ACE inhibitors on RAS in the brain, since no significant differences were found in the levels of blood pressure among the groups treated with several antihypertensive drugs. Brain penetrating ACE inhibitors might have benefits not only for the prevention but also for the treatment of mild to moderate AD with hypertension.

  7. Optimized statistical parametric mapping for partial-volume-corrected amyloid positron emission tomography in patients with Alzheimer's disease and Lewy body dementia

    NASA Astrophysics Data System (ADS)

    Oh, Jungsu S.; Kim, Jae Seung; Chae, Sun Young; Oh, Minyoung; Oh, Seung Jun; Cha, Seung Nam; Chang, Ho-Jong; Lee, Chong Sik; Lee, Jae Hong

    2017-03-01

    We present an optimized voxelwise statistical parametric mapping (SPM) of partial-volume (PV)-corrected positron emission tomography (PET) of 11C Pittsburgh Compound B (PiB), incorporating the anatomical precision of magnetic resonance image (MRI) and amyloid β (A β) burden-specificity of PiB PET. First, we applied region-based partial-volume correction (PVC), termed the geometric transfer matrix (GTM) method, to PiB PET, creating MRI-based lobar parcels filled with mean PiB uptakes. Then, we conducted a voxelwise PVC by multiplying the original PET by the ratio of a GTM-based PV-corrected PET to a 6-mm-smoothed PV-corrected PET. Finally, we conducted spatial normalizations of the PV-corrected PETs onto the study-specific template. As such, we increased the accuracy of the SPM normalization and the tissue specificity of SPM results. Moreover, lobar smoothing (instead of whole-brain smoothing) was applied to increase the signal-to-noise ratio in the image without degrading the tissue specificity. Thereby, we could optimize a voxelwise group comparison between subjects with high and normal A β burdens (from 10 patients with Alzheimer's disease, 30 patients with Lewy body dementia, and 9 normal controls). Our SPM framework outperformed than the conventional one in terms of the accuracy of the spatial normalization (85% of maximum likelihood tissue classification volume) and the tissue specificity (larger gray matter, and smaller cerebrospinal fluid volume fraction from the SPM results). Our SPM framework optimized the SPM of a PV-corrected A β PET in terms of anatomical precision, normalization accuracy, and tissue specificity, resulting in better detection and localization of A β burdens in patients with Alzheimer's disease and Lewy body dementia.

  8. Novel Point Mutations and A8027G Polymorphism in Mitochondrial-DNA-Encoded Cytochrome c Oxidase II Gene in Mexican Patients with Probable Alzheimer Disease.

    PubMed

    Loera-Castañeda, Verónica; Sandoval-Ramírez, Lucila; Pacheco Moisés, Fermín Paul; Macías-Islas, Miguel Ángel; Alatorre Jiménez, Moisés Alejandro; González-Renovato, Erika Daniela; Cortés-Enríquez, Fernando; Célis de la Rosa, Alfredo; Velázquez-Brizuela, Irma E; Ortiz, Genaro Gabriel

    2014-01-01

    Mitochondrial dysfunction has been thought to contribute to Alzheimer disease (AD) pathogenesis through the accumulation of mitochondrial DNA mutations and net production of reactive oxygen species (ROS). Mitochondrial cytochrome c-oxidase plays a key role in the regulation of aerobic production of energy and is composed of 13 subunits. The 3 largest subunits (I, II, and III) forming the catalytic core are encoded by mitochondrial DNA. The aim of this work was to look for mutations in mitochondrial cytochrome c-oxidase gene II (MTCO II) in blood samples from probable AD Mexican patients. MTCO II gene was sequenced in 33 patients with diagnosis of probable AD. Four patients (12%) harbored the A8027G polymorphism and three of them were early onset (EO) AD cases with familial history of the disease. In addition, other four patients with EOAD had only one of the following point mutations: A8003C, T8082C, C8201T, or G7603A. Neither of the point mutations found in this work has been described previously for AD patients, and the A8027G polymorphism has been described previously; however, it hasn't been related to AD. We will need further investigation to demonstrate the role of the point mutations of mitochondrial DNA in the pathogenesis of AD.

  9. Novel Point Mutations and A8027G Polymorphism in Mitochondrial-DNA-Encoded Cytochrome c Oxidase II Gene in Mexican Patients with Probable Alzheimer Disease

    PubMed Central

    Loera-Castañeda, Verónica; Sandoval-Ramírez, Lucila; Pacheco Moisés, Fermín Paul; Macías-Islas, Miguel Ángel; Alatorre Jiménez, Moisés Alejandro; González-Renovato, Erika Daniela; Cortés-Enríquez, Fernando; Célis de la Rosa, Alfredo; Velázquez-Brizuela, Irma E.

    2014-01-01

    Mitochondrial dysfunction has been thought to contribute to Alzheimer disease (AD) pathogenesis through the accumulation of mitochondrial DNA mutations and net production of reactive oxygen species (ROS). Mitochondrial cytochrome c-oxidase plays a key role in the regulation of aerobic production of energy and is composed of 13 subunits. The 3 largest subunits (I, II, and III) forming the catalytic core are encoded by mitochondrial DNA. The aim of this work was to look for mutations in mitochondrial cytochrome c-oxidase gene II (MTCO II) in blood samples from probable AD Mexican patients. MTCO II gene was sequenced in 33 patients with diagnosis of probable AD. Four patients (12%) harbored the A8027G polymorphism and three of them were early onset (EO) AD cases with familial history of the disease. In addition, other four patients with EOAD had only one of the following point mutations: A8003C, T8082C, C8201T, or G7603A. Neither of the point mutations found in this work has been described previously for AD patients, and the A8027G polymorphism has been described previously; however, it hasn't been related to AD. We will need further investigation to demonstrate the role of the point mutations of mitochondrial DNA in the pathogenesis of AD. PMID:24701363

  10. High-resolution PET studies in Alzheimer's disease

    SciTech Connect

    Kumar, A.; Schapiro, M.B.; Grady, C.; Haxby, J.V.; Wagner, E.; Salerno, J.A.; Friedland, R.P.; Rapoport, S.I. )

    1991-01-01

    Forty-seven patients with probable dementia of the Alzheimer type (DAT) and 30 healthy age-matched controls were scanned using (18F)-2-fluoro-2-deoxy-D-glucose on a Scanditronix PC 1024-7B tomograph (inplane resolution = 6 mm, axial resolution = 10 mm). Patients and controls were scanned in the resting state with their eyes patched and ears occluded. The regional cerebral metabolic rates for glucose (rCMRglc) in most major neocortical and subcortical gray matter regions, and certain metabolic ratios (rCMRglc/ calcarine rCMRglc), quantitatively discriminated even the mildly demented patients from healthy controls. The association neocortices showed metabolic abnormalities that were more severe than those in the sensorimotor and calcarine regions. All demented groups showed significant neuropsychological disturbances when compared to healthy controls. These data demonstrated widespread metabolic disturbances, particularly in the association areas, relatively early in Alzheimer's disease, and more profound involvement with disease progression.

  11. Redesigning Systems of Care for Older Adults with Alzheimer' Disease

    PubMed Central

    Callahan, Christopher M.; Sachs, Greg A.; LaMantia, Michael A.; Unroe, Kathleen T.; Arling, Greg A.; Boustani, Malaz A.

    2017-01-01

    The basic principle of care for patients with Alzheimer's disease is support for a patient-caregiver dyad. Any model of care seeking to improve the quality, efficiency, or cost of care for persons with Alzheimer's disease must attend to this principle. Models of care seeking to support this dyad began with strategies focusing mainly on the family caregiver. These models have grown in complexity to encompass team-based care that seeks to coordinate care across settings and providers of care for a defined population of patients. Most Americans in most communities, however, do not have access to these best practices models. While the effectiveness of new models of care is evidence-based, there are multiple barriers to widespread adoption including workforce limitations and the cost of practice redesign. We review the origins and content of current models and describe early efforts to improve their implementation on a broader scale. PMID:24711324

  12. Features and machine learning classification of connected speech samples from patients with autopsy proven Alzheimer's disease with and without additional vascular pathology.

    PubMed

    Rentoumi, Vassiliki; Raoufian, Ladan; Ahmed, Samrah; de Jager, Celeste A; Garrard, Peter

    2014-01-01

    Mixed vascular and Alzheimer-type dementia and pure Alzheimer's disease are both associated with changes in spoken language. These changes have, however, seldom been subjected to systematic comparison. In the present study, we analyzed language samples obtained during the course of a longitudinal clinical study from patients in whom one or other pathology was verified at post mortem. The aims of the study were twofold: first, to confirm the presence of differences in language produced by members of the two groups using quantitative methods of evaluation; and secondly to ascertain the most informative sources of variation between the groups. We adopted a computational approach to evaluate digitized transcripts of connected speech along a range of language-related dimensions. We then used machine learning text classification to assign the samples to one of the two pathological groups on the basis of these features. The classifiers' accuracies were tested using simple lexical features, syntactic features, and more complex statistical and information theory characteristics. Maximum accuracy was achieved when word occurrences and frequencies alone were used. Features based on syntactic and lexical complexity yielded lower discrimination scores, but all combinations of features showed significantly better performance than a baseline condition in which every transcript was assigned randomly to one of the two classes. The classification results illustrate the word content specific differences in the spoken language of the two groups. In addition, those with mixed pathology were found to exhibit a marked reduction in lexical variation and complexity compared to their pure AD counterparts.