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Sample records for alzheimers disease patients

  1. Assessment of visual impairment in patients with Alzheimer's disease.

    PubMed

    Sadun, A A; Borchert, M; DeVita, E; Hinton, D R; Bassi, C J

    1987-08-15

    We examined five patients with Alzheimer's disease who complained of poor vision. Two patients had mild Alzheimer's disease; they complained of problems with reading and of "bumping into things," yet both had normal visual acuities. One patient with moderate Alzheimer's disease had abnormal eye movements, visual-evoked potentials, and contrast sensitivity. The other two patients had severe Alzheimer's disease. Despite difficulties in performing the examination, we were able to see moderate impairments in visual acuity and visual fields, as well as marked dyschromatopsia, severe deficits in contrast sensitivity, and markedly abnormal eye movements and visual-evoked potentials.

  2. 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. PMID:26921134

  3. 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.

  4. Macrophage and polymorphonuclear leukocyte function in patients with Alzheimer disease.

    PubMed

    Cameron, D J; Durst, G G; Majeski, J A

    1985-01-01

    Monocyte derived macrophages and polymorphonuclear leukocytes (PMNs) isolated from the peripheral blood of thirteen patients with Alzheimer disease were studied for their cytotoxic effects on a sensitive allogenic tumor target. PMN cells from 11 of the 13 patients with Alzheimer disease were able to kill the tumor cells. In addition, the macrophages from 12 of the 13 Alzheimer disease patients were cytotoxic towards the tumor targets. Four of these patients possessed a plasma inhibitory factor which was capable of suppressing macrophage mediated cytotoxicity. When the lymphocytes from these patients were studied for their ability to be stimulated with the specific antigen, streptokinase, to produce macrophage activating factor (MAF), only 5 of the 13 patients studied possessed lymphocytes which were capable of producing MAF. Thus, the only immunological defect in Alzheimer disease patients which was observed in this study was in the ability of the lymphocytes to synthesize MAF. PMID:4084662

  5. Support Group Counseling for Caregivers of Alzheimer's Disease Patients.

    ERIC Educational Resources Information Center

    Hinkle, J. Scott

    1991-01-01

    Describes Alzheimer's disease and the burdens that caregivers encounter in dealing with Alzheimer's patients. Presents information concerning support group counseling for caregivers, their particular needs, and special family issues. Emphasizes that relationships between caregivers and support group counselors are crucial to successful…

  6. 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…

  7. Alzheimer disease

    MedlinePlus

    Senile dementia - Alzheimer type (SDAT); SDAT; Dementia - Alzheimer ... The exact cause of Alzheimer disease (AD) is not known. Research shows that certain changes in the brain lead to AD. You are more likely ...

  8. "Will I get Alzheimer disease?" when cognitively normal patients ask to be tested for Alzheimer disease.

    PubMed

    Snider, B Joy; Buckles, Virginia D

    2013-04-01

    This article presents the case of a cognitively normal patient who is requesting a procedure (amyloid imaging) recently approved for the diagnosis of Alzheimer disease (AD) in patients with cognitive impairment. The predictive value of this test in unaffected people is not clearly established. Knowing the results of the test will have no effect on therapeutic options, although the patient may make lifestyle decisions based on the results. There is potential risk to the patient in terms of insurability, employability, and psychological consequences. Physicians will face this situation with increasing frequency as the AD biomarker field progresses.

  9. Stereological quantification of the cerebellum in patients with Alzheimer's disease.

    PubMed

    Andersen, Kjeld; Andersen, Birgitte Bo; Pakkenberg, Bente

    2012-01-01

    Nonquantitative studies indicate that the cerebellum is neuropathologically affected in Alzheimer's disease; however, no quantitative studies on the subject have yet been conducted. Ten cerebella from elderly female subjects with severe Alzheimer's disease and 10 age- and gender-matched controls were examined. The cerebellum was divided into 5 regions and the Purkinje and granule cell number and density, cortical volume, molecular and granular layer volume and thickness, white matter volume, surface area, and the Purkinje cell gradient were stereologically estimated. There was no significant difference between the groups in Purkinje or granule cell number or density, and no overall difference in Purkinje cell gradient. However, there was a significant 12.7% reduction in total cerebellar volume in the Alzheimer's group and significant localized differences between the groups regarding other parameters. The relative lack of neuropathological changes in the cerebellum of severely demented Alzheimer's patients suggests that neuronal cell bodies on a global scale apparently still are intact. PMID:20728248

  10. Joint Storytelling by Patients with Alzheimer's Disease and Their Spouses.

    ERIC Educational Resources Information Center

    Kemper, Susan; And Others

    1995-01-01

    Discusses personal narratives of subjects with Alzheimer's disease and their spouses. Notes that solo narratives were gathered from patients and spouses separately, and then joint narratives were gathered. Compares patients' ability to provide settings in their solo narrative to their ability to supply information when prompted by spouses. Finds…

  11. 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…

  12. Assessing Impact on Family Caregivers to Alzheimer's Disease Patients.

    ERIC Educational Resources Information Center

    Talkington-Boyer, Shannon; Snyder, Douglas K.

    1994-01-01

    Examined impact of caregiving among 110 caregivers to aging family member with Alzheimer's disease. Family caregivers' appraisals along dimensions of subjective burden, negative impact, caregiving satisfaction, and caregiver mastery were correlated with extent of memory and behavior problems of patient and caregivers' coping style, locus of…

  13. 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.

  14. Alzheimer's disease care management plan: maximizing patient care.

    PubMed

    Treinkman, Anna

    2005-03-01

    Nurse practitioners have the potential to significantly impact the care of patients with dementia. Healthcare providers can now offer patients medications that will control symptoms and prolong functioning. As a result of ongoing contact with patients, NPs play an important role in assessing and screening patients for AD and educating the patients, families, and caregivers about the disease. Alzheimer's disease is a chronic, progressive illness that requires long-term management. Nurse practitioners should be familiar with available medications and appreciate the need to individualize therapy to maximize efficacy and minimize potential adverse drug reactions.

  15. [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.

  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. PMID:18674439

  17. [Verbal ability of Alzheimer's disease patients and very elderly control patients using the Aachen aphasia test].

    PubMed

    Ecklin, R; Schönenberger, P M

    1992-01-01

    We assessed language function, using the Aachen aphasia test (AAT), in 14 subjects with Alzheimer's disease and 6 control patients. Aphasia did not occur in control patients, but in 11 of 14 Alzheimer's disease patients. Impairment of object naming was the most prevalent abnormality. Performance in AAT subtests repetition, written language, object naming, comprehension and token test correlated strongly with Mini-Mental State scores.

  18. 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.

  19. Navigating patients and caregivers through the course of Alzheimer's disease.

    PubMed

    Aupperle, Peter M

    2006-01-01

    Alzheimer's disease (AD) prevalence rates in the United States are expected to triple over the next 50 years, a consequence of the overall aging of the U.S. population. Because of the profound and far-reaching impact of AD, this projected increase in prevalence is expected to pose a tremendous challenge. Alzheimer's disease results in the cognitive and functional deterioration of the affected patient, and behavioral disturbances frequently accompany the disease. Furthermore, because of its progressive and debilitating nature, AD takes a dramatic emotional, physical, and financial toll on the patient's primary caregiver. Nonetheless, despite the burden experienced by both patients and caregivers, strategies for minimizing the negative consequences of AD are well characterized. Central to the successful management of AD is the prompt and accurate diagnosis of the disease, with current guidelines calling for a 2-tiered approach in which patients first undergo screening using a brief cognitive assessment tool, followed by a comprehensive battery of physical, psychological, and neurologic tests if signs of possible cognitive impairment are evident upon screening. Once a conclusive diagnosis of AD has been made, the development of a disease management approach targeting the needs of the patient and his or her caregiver becomes a primary concern. Pharmacologic interventions may play an important role in such approaches, as agents such as cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine have been associated with favorable outcomes for patients and caregivers alike. However, in addition to the therapeutic benefits of these agents, associated side effects and potential drug-drug interactions must also factor into decisions regarding the pharmacologic treatment of AD.

  20. The neurologic examination in patients with probable Alzheimer's disease.

    PubMed

    Huff, F J; Boller, F; Lucchelli, F; Querriera, R; Beyer, J; Belle, S

    1987-09-01

    Abnormal findings on a standardized neurologic examination were compared between patients with a clinical diagnosis of probable Alzheimer's disease (AD) and healthy control subjects. Aside from mental status findings, the most useful examination findings for differentiating AD from control subjects were the presence of release signs, olfactory deficit, impaired stereognosis or graphesthesia, gait disorder, tremor, and abnormalities on cerebellar testing. These abnormalities probably reflect the different areas of the central nervous system that are affected pathologically in AD. In the clinical diagnosis of AD, particular attention should be given to these aspects of the neurologic examination.

  1. Functional assessment staging (FAST) in Korean patients with Alzheimer's disease.

    PubMed

    Na, Hae-Ri; Kim, Sang-Yun; Chang, Young-Hee; Park, Moon-Ho; Cho, Sung-Tae; Han, Il-Woo; Kim, Tae-You; Hwang, Sul-A

    2010-01-01

    Functional Assessment Staging (FAST) was devised to meet the need for a more brief patient-derived rating scale for evaluating changes in functional performance and activities of daily living skills in all the stages of Alzheimer's disease (AD). FAST was administered to 464 patients with probable AD according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. The patients were also evaluated using the Korean version of the Mini-Mental Status Examination (K-MMSE), the Clinical Dementia Rating (CDR), the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Global Deterioration Scale (GDS), the Barthel Activities of Daily Living (B-ADL), and the Seoul-Instrumental Activities of Daily Living (S-IADL). For patients with moderate to severe dementia, the Korean versions of the Severe Impairment Battery (SIB-Ko) and Baylor profound mental status examination (BPMSE-Ko) were also administered. There were significant correlations between the FAST and the K-MMSE scores (r= - 0.71, p< 0.001), between the FAST and the SIB-Ko scores (r= - 0.54, p< 0.001) and between the FAST and the BPMSE-Ko scores (r=- 0.46, p< 0.001). The FAST was also correlated with the CDR, the CDR-SB, the B-ADL, and the S-IADL (p< 0.001). Ultimately, FAST is a reliable and valid assessment technique for evaluating functional deterioration in AD patients throughout the disease course. Moreover, the findings of the present study suggest that the FAST elucidates a characteristic pattern of progressive, ordinal, and functional decline in AD in Korean AD patients with dementia. PMID:20847407

  2. 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 ...

  3. Endostatin level in cerebrospinal fluid of patients with Alzheimer's disease.

    PubMed

    Salza, Romain; Oudart, Jean-Baptiste; Ramont, Laurent; Maquart, François-Xavier; Bakchine, Serge; Thoannès, Henri; Ricard-Blum, Sylvie

    2015-01-01

    The aim of this study was to measure the level of endostatin, a fragment of collagen XVIII that accumulates in the brain of patients with Alzheimer's disease (AD), in the cerebrospinal fluids (CSF) of patients with neurodegenerative diseases. The concentrations of total protein, endostatin, amyloid-β1-42 peptide, tau, and hyperphosphorylated tau proteins were measured by enzyme-linked immunosorbent assay in CSF of patients with AD (n = 57), behavioral frontotemporal dementia (bvFTD, n = 22), non AD and non FTD dementia (nAD/nFTD, n = 84), and 45 subjects without neurodegenerative diseases. The statistical significance of the results was assessed by Mann-Whitney and Kruskal and Wallis tests, and by ROC analysis. The concentration of endostatin in CSF was higher than the levels of the three markers of AD both in control subjects and in patients with neurodegenerative diseases. The endostatin/amyloid-β1-42 ratio was significantly increased in patients with AD (257%, p < 0.0001) and nAD/nFTD (140%, p < 0.0001) compared to controls. The endostatin/tau protein ratio was significantly decreased in patients with AD (-49%, p < 0.0001) but was increased in bvFTD patients (89%, p < 0.0001) compared to controls. In the same way, the endostatin/hyperphosphorylated tau protein ratio was decreased in patients with AD (-21%, p = 0.0002) but increased in patients with bvFTD (81%, p = 0.0026), compared to controls. The measurement of endostatin in CSF and the calculation of its ratio relative to well-established AD markers improve the diagnosis of bvFTD patients and the discrimination of patients with AD from those with bvFTD and nAD/nFTD. PMID:25408220

  4. 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.

  5. Delusions in Patients with Alzheimer's Disease: A Multidimensional Approach.

    PubMed

    D'Onofrio, Grazia; Panza, Francesco; Sancarlo, Daniele; Paris, Francesco F; Cascavilla, Leandro; Mangiacotti, Antonio; Lauriola, Michele; Paroni, Giulia H; Seripa, Davide; Greco, Antonio

    2016-01-01

    In Alzheimer's disease (AD) patients with delusions, clinical outcomes and mortality result from a combination of psychological, biological, functional, and environmental factors. We determined the effect of delusions on mortality risk, clinical outcomes linked to comprehensive geriatric assessment (CGA), cognitive, depressive, and neuropsychiatric symptoms (NPS) in 380 consecutive AD patients with Mini-Mental State Examination, Clinical Dementia Rating scale, 15-item Geriatric Depression Scale, and Neuropsychiatric Inventory (NPI), assessing one-year mortality risk using the Multidimensional Prognostic Index (MPI). We included 121 AD patients with delusions (AD-D) and 259 AD patients without delusions (AD-noD). AD-D patients were significantly older, with higher age at onset and cognitive impairment, a more severe stage of dementia, and more depressive symptoms than AD-noD patients. Disease duration was slightly higher in AD-D patients than in those without delusions, although this difference was not statistically significant. At CGA, AD-D patients showed a higher grade of disability in basic and instrumental activities of daily living, and an increased risk of malnutrition and bedsores. The two groups of patients significantly differed in MPI score (AD-D: 0.65 versus AD-noD: 0.51, p <  0.0001) and MPI grade. AD-D patients showed also a significant higher score in NPI of the following NPS than AD-noD patients: hallucinations, agitation/aggression, depression mood, apathy, irritability/lability, aberrant motor activity, sleep disturbances, and eating disorders. Therefore, AD-D patients showed higher dementia severity, and higher impairment in cognitive and depressive symptoms, and several neuropsychiatric domains than AD-noD patients, and this appeared to be associated with higher multidimensional impairment and increased risk of mortality. PMID:26890768

  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's disease.

    PubMed

    De-Paula, Vanessa J; Radanovic, Marcia; Diniz, Breno S; Forlenza, Orestes V

    2012-01-01

    Alzheimer's disease (AD) is a chronic neurodegenerative disease with well-defined pathophysiological mechanisms, mostly affecting medial temporal lobe and associative neocortical structures. Neuritic plaques and neurofibrillary tangles represent the pathological hallmarks of AD, and are respectively related to the accumulation of the amyloid-beta peptide (Aβ) in brain tissues, and to cytoskeletal changes that arise from the hyperphosphorylation of microtubule-associated Tau protein in neurons. According to the amyloid hypothesis of AD, the overproduction of Aβ is a consequence of the disruption of homeostatic processes that regulate the proteolytic cleavage of the amyloid precursor protein (APP). Genetic, age-related and environmental factors contribute to a metabolic shift favoring the amyloidogenic processing of APP in detriment of the physiological, secretory pathway. Aβ peptides are generated by the successive cleavage of APP by beta-secretase (BACE-1) and gamma-secretase, which has been recently characterized as part of the presenilin complex. Among several beta-amyloid isoforms that bear subtle differences depending on the number of C-terminal amino acids, Aβ (1-42) plays a pivotal role in the pathogenesis of AD. The neurotoxic potential of the Aβ peptide results from its biochemical properties that favor aggregation into insoluble oligomers and protofibrils. These further originate fibrillary Aβ species that accumulate into senile and neuritic plaques. These processes, along with a reduction of Aβ clearance from the brain, leads to the extracellular accumulation of Aβ, and the subsequent activation of neurotoxic cascades that ultimately lead to cytoskeletal changes, neuronal dysfunction and cellular death. Intracerebral amyloidosis develops in AD patients in an age-dependent manner, but recent evidence indicate that it may be observed in some subjects as early as in the third or fourth decades of life, with increasing magnitude in late middle age

  8. [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.

  9. [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. PMID:25579215

  10. Histopathology and APOE genotype of the first Alzheimer disease patient, Auguste D.

    PubMed

    Graeber, M B; Kösel, S; Grasbon-Frodl, E; Möller, H J; Mehraein, P

    1998-03-01

    Alois Alzheimer published two papers on the disease which was named after him by Emil Kraepelin in 1910. Each of these papers contains clinical and pathological data on a patient Alzheimer had seen at the hospital. We have previously reported on the rediscovery of tissue sections from Alzheimer's second published case of Alzheimer disease, Johann F., which probably gave the disease its name (Neurogenetics 1997; 1:73-80). Here, we describe the histopathology and APOE genotype of Alois Alzheimer's first patient, Auguste D. As in the case of Johann F., a large number of tissue sections belonging to Alzheimer's laboratory, which was later headed by Spielmeyer, were found among material kept at the Institute of Neuropathology of the University of Munich. As described by Alzheimer in his original report (Allg Zeitschr Psychiatr 1907; 64:146-148), there were numerous neurofibrillary tangles and many amyloid plaques, especially in the upper cortical layers of this patient. Yet, there was no microscopic evidence for vascular, i.e., arteriosclerotic, lesions. Interestingly, Alzheimer's histological preparations did not include the hippocampus or entorhinal region. The APOE genotype of this patient was shown to be epsilon3/epsilon3 by PCR-based restriction enzyme analysis, indicating that mutational screening of the tissue is feasible. The historical importance of the case of Auguste D. lies in the fact that it marks the beginning of research into Alzheimer disease. In addition, neurofibrillary tangles were first described in this brain.

  11. Loss of semantic associative categories in patients with Alzheimer's disease.

    PubMed

    Passafiume, Domenico; De Federicis, Lucia Serenella; Carbone, Gabriele; Di Giacomo, Dina

    2012-01-01

    Deterioration of semantic memory is one of the primary neuropsychological deficits caused by Alzheimer's disease (AD). In this study, we hypothesize that the breakdown of semantic memory in the mild-to-moderate stage of AD is due to the disruption of the semantic network that links the concepts. Furthermore, the loss of these links is not homogeneous through the semantic association categories (i.e., Superordinate, Contiguity, Part/Whole, Attribute, Function). Twenty-two subjects (11 patients with mild-to-moderate dementia and 11 control subjects matched on demographics) participated in the study. Both controls and patients with AD underwent extensive neuropsychological evaluation and three experimental tasks: (1) Naming Task, (2) Semantic Association Task, and (3) Semantic Knowledge Task. Results showed that: (1) The AD group was significantly different from the normal controls group in all the experimental tasks; (2) the Semantic Association Task was significantly worse than the other tasks; (3) for the AD group, the scores of the Function and Part/Whole association categories were higher than in the other categories; and (4) living stimuli were more impaired than nonliving. These data confirm prior research showing the semantic association is differently impaired in AD patients. PMID:23373643

  12. Plasmin system of Alzheimer's disease patients: CSF analysis.

    PubMed

    Martorana, Alessandro; Sancesario, Giulia M; Esposito, Zaira; Nuccetelli, Marzia; Sorge, Roberto; Formosa, Amanda; Dinallo, Vincenzo; Bernardi, Giorgio; Bernardini, Sergio; Sancesario, Giuseppe

    2012-07-01

    Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by the extracellular deposit of Amyloid beta (Aβ), mainly of the Amyloid beta(1-42) (Aβ(1-42)) peptide in the hippocampus and neocortex leading to progressive cognitive decline and dementia. The possible imbalance between the Aβ production/degradation process was suggested to contribute to the pathogenesis of AD. Among others, the serine protease plasmin has shown to be involved in Aβ(1-42) clearance, a hypothesis strengthened by neuropathological studies on AD brains. To explore whether there is a change in plasmin system in CSF of AD patients, we analyzed CSF samples from AD and age-matched controls, looking at plasminogen, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) protein levels and t-PA and urokinase plasminogen activator (u-PA) enzymatic activities. We also measured Aβ(1-42), total-tau and phospho-tau (181) CSF levels and sought for a possible relationship between them and plasmin system values. Our findings showed that t-PA, plasminogen and PAI-1 levels, as t-PA enzymatic activity, remained unchanged in AD with respect to controls; u-PA activity was not detected. We conclude that CSF analysis of plasminogen system does not reflect changes observed post-mortem. Unfortunately, the CSF detection of plasmin system could not be a useful biomarker for either AD diagnosis or disease progression. However, these findings do not exclude the possible involvement of the plasmin system in AD.

  13. 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.

  14. 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. PMID:26907471

  15. 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.

  16. High-frequency cranial electrostimulation (CES) in patients with probable Alzheimer's disease.

    PubMed

    Scherder, Erik J A; van Tol, M J; Swaab, D F

    2006-07-01

    In a previous study, low-frequency cranial electrostimulation did not improve cognition and (affective) behavior in patients with probable Alzheimer's disease. In the present study, 21 Alzheimer's disease patients, divided into an experimental (n = 11) and a control group (n = 10), were treated for 30 mins/day, 5 days/wk, for 6 wks with high-frequency cranial electrostimulation. Similar to the previous study, no improvements on cognition and (affective) behavior were found.

  17. 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

  18. Efficacy of Music Therapy in Treatment for the Patients with Alzheimer's Disease

    PubMed Central

    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. PMID:23056992

  19. 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. PMID:23056992

  20. Neuropathology of Alzheimer's disease.

    PubMed

    Perl, Daniel P

    2010-01-01

    Alois Alzheimer first pointed out that the disease which would later bear his name has a distinct and recognizable neuropathological substrate. Since then, much has been added to our understanding of the pathological lesions associated with the condition. The 2 primary cardinal lesions associated with Alzheimer's disease are the neurofibrillary tangle and the senile plaque. The neurofibrillary tangle consists of abnormal accumulations of abnormally phosphorylated tau within the perikaryal cytoplasm of certain neurons. The senile plaque consists of a central core of beta-amyloid, a 4-kD peptide, surrounded by abnormally configured neuronal processes or neurites. Other neuropathological lesions are encountered in cases of Alzheimer's disease, but the disease is defined and recognized by these 2 cardinal lesions. Other lesions include poorly understood changes such as granulovacuolar degeneration and eosinophilic rodlike bodies (Hirano bodies). The loss of synaptic components is a change that clearly has a significant impact on cognitive function and represents another important morphological alteration. It is important to recognize that distinguishing between Alzheimer's disease, especially in its early stages, and normal aging may be very difficult, particularly if one is examining the brains of patients who died at an advanced old age. It is also noted that instances of pure forms of Alzheimer's disease, in the absence of other coexistent brain disease processes, such as infarctions or Parkinson's disease-related lesions, are relatively uncommon, and this must be taken into account by researchers who employ postmortem brain tissues for research.

  1. 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.

  2. [Update on Alzheimer's disease].

    PubMed

    Dubois, B

    2009-03-01

    As the general population ages, the prevalence of Alzheimer's disease increases steadily. In France, 850,000 people are affected, with an annual incidence of 165,000 new cases. It is estimated that in 2020, 1.2 million people will be concerned in France. Nearly half of these patients, about 400,000, will have moderate to severe disease. These figures, issuing from the Eurodem group and the Paquid study, are estimates but clearly forecast an increase in upcoming years. While the disease generally affects elderly subjects, it is also known to occur early, before the age of 60. Nearly 20,000 patients will have an early onset form of the disease. Alzheimer's disease is first and foremost a brain disease, with lesions starting early in life. These early onset forms raise difficult diagnostic problems since these patients' problems are often mistakenly thought to arise from psychiatric disorders and treated as such in institutions inadapted to the patients' conditions.

  3. 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.

  4. 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.…

  5. Genetics Home Reference: Alzheimer disease

    MedlinePlus

    ... and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center MalaCards: alzheimer disease MalaCards: alzheimer disease risk factor Merck Manual Consumer Version: Alzheimer Disease Quick Facts ...

  6. Are peripheral blood cells from patients with Alzheimer disease more sensitive to apoptotic stimuli?

    PubMed

    Bergman, Michael; Salman, Hertzel; Beloosesky, Yichayaou; Djaldetti, Meir; Bessler, Hanna

    2002-01-01

    One of the reasons for the increased susceptibility to infections in patients with Alzheimer disease may be enhanced apoptotic death of their peripheral leukocytes. If this is the case, the enhanced apoptosis may be due to components in the patients' sera or to an increased sensitivity of the cells to apoptotic stimuli. To examine this possibility, the percentage of apoptotic cells in the peripheral blood mononuclear cells (PBMC) from 12 patients with Alzheimer disease was compared with that of 12 age-matched non-demented persons and 12 middle-aged healthy control subjects. In addition, the effect of sera from subjects in the three groups on the apoptosis, interleukin (IL)-1beta, IL-2, IL-6, IL-10, and tumor necrosis factor (TNF)alpha production by peripheral blood cells from healthy control subjects was examined. It was found that the percentage of apoptotic PBMC from patients with Alzheimer disease was higher than that from the remaining two groups. However, incubation of control cells with sera from patients with Alzheimer disease and non-demented elderly persons did not affect the number of apoptotic cells. Sera from patients with Alzheimer disease and non-demented elderly subjects caused an increase in IL-2 and a decrease in IL-10 production by PBMC from middle-aged control subjects but did not affect IL-1beta, IL-6, and TNFalpha secretion, indicating alterations of the immune system related to aging.

  7. Takotsubo cardiomyopathy in an elderly patient with severe Alzheimer's disease: a case report.

    PubMed

    Cerri, Anna Paola; Teruzzi, Fabiola; Gregorio, Marianna; Bellelli, Giuseppe; Annoni, Giorgio

    2012-03-01

    We report on an 80-year-old woman with Alzheimer's disease who presented with Takotsubo cardiomyopathy. As usual for this condition, our patient showed clinical symptoms of chest pain, electrocardiographic changes, elevated myocardial markers, and transient left ventricular apical ballooning in the absence of significant coronary artery disease. Because Takotsubo cardiomyopathy is frequently associated with emotional stress, which triggers an increase in circulating catecholamines, our case suggests that this event should not be neglected in Alzheimer's disease patients and promotes the adoption of a "prosthetic" approach for individuals with dementia.

  8. Prediabetes and Alzheimer's Disease

    PubMed Central

    Bitra, V. R.; Rapaka, Deepthi; Akula, Annapurna

    2015-01-01

    Aging patients with diabetes are at higher risk of developing Alzheimer's disease. Emerging evidences demonstrate the role of brain insulin resistance, which is a key mediator in prediabetes and diabetes mellitus that may lead to Alzheimer's disease. Insulin and insulin-like growth factors regulate many biological processes such as axonal growth, protein synthesis, cell growth, gene expression, proliferation, differentiation, and development. Among these, the energy metabolism and synaptic plasticity are the major transduction processes regulated by insulin, which are the core objectives for learning and memory. It was also proposed that hyper insulinemia induced insulin resistance results in injury to the central nervous system by the activation of glycogen synthase kinase 3β which is the key ailment in the cognitive decline. Hence, the endogenous brain specific insulin impairments and signaling account for the majority of Alzheimer's abnormalities. PMID:26798163

  9. Sustained choroid plexus function in human elderly and Alzheimer's disease patients.

    PubMed

    Spector, Reynold; Johanson, Conrad E

    2013-09-24

    We and other investigators have postulated deterioration of essential choroid plexus (CP) functions in some elderly and especially Alzheimer's disease patients based on apparent anatomical, histological and pathological changes in CP. We have termed this putative phenomenon CP failure. By focusing on four essential energy-requiring CP functions, specifically ascorbic acid (AA) and folate transport from blood into CSF, transthyretin synthesis and secretion into CSF, and electrolyte/acid-base balance in CSF, we were able to evaluate the hypothesis of CP failure by reviewing definitive human data. In both healthy elderly and Alzheimer's disease patients, the CP functions normally to transport AA and folates actively from blood into CSF, synthesize and secrete transthyretin into CSF, and maintain CSF acid-base balance and ion concentrations. These human CSF compositional data provide no support for the notion of CP failure in elderly humans and Alzheimer's disease patients.

  10. 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.

  11. 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…

  12. 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…

  13. [Alzheimer's disease and depression].

    PubMed

    Gallarda, T

    1999-11-01

    Alzheimer's disease is the most frequent cause of dementia (60% of all dementias) and affects nearly 300,000 people in France. Alzheimer's disease is a disease of the elderly which generally begins after 60 years and whose prevalence increases markedly after age 75 years. The elderly population is increasing in all Western countries. Alzheimer's disease thus constitutes a veritable emergent public health problem. The rapid inflation of the epidemiological and etiopathogenetic data have contributed to enhanced nosographic definition and finer semiological characterization of the disease. Thus, the classic concept of senile dementia has been totally abandoned. In contrast, the concept of depressive pseudodementia as defined by Kiloh (1961) remains present in the "psychiatric culture". The concept refers to rare clinical situations in which the controversial concept of "test therapy" with antidepressants retains, in the author's opinion, some utility. Depressive or psychobehavioral signs and symptoms frequently inaugurate Alzheimer's disease giving rise to first-line psychiatric management. The use of multidimensional evaluation instruments such as the neuropsychiatric inventory (NPI) has enabled demonstration of the signs and symptoms and their quantification through the course of the disease. In the dementia stage, the psychobehavioral symptoms are related to the patient's awareness of the degradation in his intellectual functions and the loss of independence and to specific neuropathological lesions responsible for "frontal deafferentation". Certain clinical forms of depression of late onset are also characterized by symptoms reflecting hypofrontal signs (blunted affect, apathy, defective initiative, etc.) and severe cognitive disorders. Those depressions are associated with risk factors shared with Alzheimer's disease (sex, age, vascular function, APOE 4) and constitute a risk factor for progression to dementia, requiring regular clinical and neuropsychological

  14. [Immunotherapy for Alzheimer's disease].

    PubMed

    Falkentoft, Alexander Christian; Hasselbalch, Steen Gregers

    2016-01-18

    Passive anti-beta-amyloid (Aß) immunotherapy has been shown to clear brain Aß deposits. Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD. Solanezumab and new monoclonal antibodies are being tested in patients with prodromal and preclinical AD in search for a disease-modifying treatment. PMID:26815584

  15. 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.

  16. 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…

  17. 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…

  18. Simple Method for Evaluation of Planum Temporale Pyramidal Neurons Shrinkage in Postmortem Tissue of Alzheimer Disease Patients

    PubMed Central

    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. PMID:24719875

  19. 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.

  20. Personality changes in Alzheimer's disease.

    PubMed

    Chatterjee, A; Strauss, M E; Smyth, K A; Whitehouse, P J

    1992-05-01

    How personality changes in Alzheimer's disease is not well understood. Accentuations of premorbid personality, systematic shifts in personality traits, and specific personality changes affecting subtypes of patients have been postulated. To investigate which of these alternatives occurs in Alzheimer's disease, caregivers were given a comprehensive personality inventory standardized for use by informants. Caregivers observed more neurotic, less extroverted, and less conscientious behavior. To a smaller extent, patients with Alzheimer's disease were reported as becoming less agreeable and less open. The changes in reports of neuroticism, extroversion, agreeableness, and openness suggested consistent systematic shifts across all patients. Patients with depressive features were reported to have been more neurotic; those with paranoid delusions were reported as having been more hostile. Premorbid personality traits may predispose to subsequent psychiatric symptoms in Alzheimer's disease.

  1. Immunotherapy for Alzheimer's disease.

    PubMed

    Farlow, Martin R; Brosch, Jared R

    2013-08-01

    The immune system plays a significant role in Alzheimer disease (AD). β-Amyloid deposition in the cortex is thought to be an initiating event in AD and the widely believed amyloid hypothesis proposes removal of amyloid may delay disease progression. Human trials of active or passive immune agents have failed to show benefit and increased adverse events of vasogenic edema and microhemorrhages. Evidence suggests the illness may be too advanced by the time patients are symptomatic with dementia. Future directions include better understanding of how and where immunotherapies should be targeted and treating patients at earlier stages of the illness.

  2. Alzheimer's Disease

    MedlinePlus

    ... risk of urinary tract and other serious infections. Malnutrition or dehydration: People who have Alzheimer’s disease may ... swallow. It’s important to watch for signs of malnutrition. If you think that a loved one might ...

  3. [Activity of peptidyl-dipeptidase A and carboxypeptidase N in the serum of patients with Alzheimer disease].

    PubMed

    Solov'ev, V B; Gengin, M T

    2007-01-01

    The activity of peptidyl-dipeptidase A and carboxypeptidase N taking part in peptide metabolism in the serum of patients with Alzheimer disease were studied. The role of these enzymes in the metabolism of neuropeptides and beta-amyloid at the Alzheimer disease was discussed.

  4. Detection of oxidative DNA damage in lymphocytes of patients with Alzheimer's disease.

    PubMed

    Kadioglu, Ela; Sardas, Semra; Aslan, Selcuk; Isik, Erdal; Esat Karakaya, Ali

    2004-01-01

    Oxidative damage to DNA may play an important role in both normal ageing and in neurodegenerative diseases. The deleterious consequences of excessive oxidations and the pathophysiological role of reactive oxygen species have been intensively studied in Alzheimer's disease. Although the role of oxidative stress in the aetiology of Alzheimer's disease is still not clear, the detection of an increased damage status in the cells of patients could have important therapeutic implications. The levels of oxidative damage in peripheral lymphocytes of 24 Alzheimer's disease patients and of 21 age-matched controls were determined by comet assay applied to freshly isolated blood samples with oxidative lesion-specific DNA repair endonucleases (endonuclease III for oxidized pyrimidines, formamidopyrimidine glycosylase for oxidized purines). It was demonstrated that Alzheimer's disease is associated with elevated levels of oxidized pyrimidines and purines (p<0.0001) as compared with age-matched control subjects. It was also demonstrated that the comet assay is useful as a biomarker of oxidative DNA damage when used with oxidative lesion-specific enzymes.

  5. 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…

  6. [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. PMID:24908841

  7. [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.

  8. Alternative splicing of the beta A4 amyloid gene of Alzheimer's disease in cortex of control and Alzheimer's disease patients.

    PubMed

    König, G; Salbaum, J M; Wiestler, O; Lang, W; Schmitt, H P; Masters, C L; Beyreuther, K

    1991-02-01

    An S1 nuclease protection assay was designed to study the splicing pattern of the alternatively spliced beta A4 amyloid gene (APP gene) of Alzheimer's disease (AD). We determined the splicing pattern of the APP gene in fetal, adult, aged adult and AD human cortex. The results suggest that alternative splicing of the APP gene in AD is not significantly different from age-matched controls, but distinct from the developing fetal brain.

  9. Effect of Psychotropic Drugs on Development of Diabetes Mellitus in Patients With Alzheimer's Disease.

    PubMed

    Chang, Ki Jung; Hong, Chang Hyung; Lee, Yunhwan; Lee, Kang Soo; Roh, Hyun Woong; Back, Joung Hwan; Jung, Young Ki; Lim, Ki Young; Noh, Jai Sung; Kim, Hyun Chung; Choi, Seong Hye; Kim, Seong Yoon; Na, Duk L; Seo, Sang Won; Lee, Soojin; Son, Sang Joon

    2015-06-01

    We aimed to examine risk of diabetes mellitus (DM) among older adults with Alzheimer's disease receiving 3 types of psychotropic drugs, that is, antipsychotics, antidepressants, and sedative anxiolytics. We retrospectively analyzed data from a hospital-based Clinical Research Center for Dementia of South Korea (CREDOS) study conducted between January 1, 2008 and December 31, 2012. Participants (n = 3042) with Alzheimer's disease were aged 65 or older and had no preexisting history of DM. Development of DM was identified using claims for initiating at least 1 prescription of antidiabetic medications or a diagnosis of DM during the follow-up period. Cox proportional hazards regression was used to demonstrate the Hazard ratio of DM in use of each psychotropic drug. Among the 3042 participants, 426 patients (14.0%) developed DM, representing an incidence rate of 5.2/100 person-years during an average 2.9 years of follow-up period. Among the 3 types of psychotropic drugs, antipsychotic users had a significantly higher risk of DM (hazard ratio = 1.74, 95% confidence interval = 1.10, 2.76) than nonusers, after adjusting covariates. Antidepressants and sedative anxiolytics did not achieve statistical significance. These results suggested that the diabetes risk was elevated in Alzheimer patients on antipsychotic treatment. Therefore, patients with Alzheimer's disease receiving antipsychotic treatment should be carefully monitored for the development of DM.

  10. Effect of Psychotropic Drugs on Development of Diabetes Mellitus in Patients With Alzheimer's Disease

    PubMed Central

    Chang, Ki Jung; Hong, Chang Hyung; Lee, Yunhwan; Lee, Kang Soo; Roh, Hyun Woong; Back, Joung Hwan; Jung, Young Ki; Lim, Ki Young; Noh, Jai Sung; Kim, Hyun Chung; Choi, Seong Hye; Kim, Seong Yoon; Na, Duk L.; Seo, Sang Won; Lee, Soojin; Son, Sang Joon

    2015-01-01

    Abstract We aimed to examine risk of diabetes mellitus (DM) among older adults with Alzheimer's disease receiving 3 types of psychotropic drugs, that is, antipsychotics, antidepressants, and sedative anxiolytics. We retrospectively analyzed data from a hospital-based Clinical Research Center for Dementia of South Korea (CREDOS) study conducted between January 1, 2008 and December 31, 2012. Participants (n = 3042) with Alzheimer's disease were aged 65 or older and had no preexisting history of DM. Development of DM was identified using claims for initiating at least 1 prescription of antidiabetic medications or a diagnosis of DM during the follow-up period. Cox proportional hazards regression was used to demonstrate the Hazard ratio of DM in use of each psychotropic drug. Among the 3042 participants, 426 patients (14.0%) developed DM, representing an incidence rate of 5.2/100 person-years during an average 2.9 years of follow-up period. Among the 3 types of psychotropic drugs, antipsychotic users had a significantly higher risk of DM (hazard ratio = 1.74, 95% confidence interval = 1.10, 2.76) than nonusers, after adjusting covariates. Antidepressants and sedative anxiolytics did not achieve statistical significance. These results suggested that the diabetes risk was elevated in Alzheimer patients on antipsychotic treatment. Therefore, patients with Alzheimer's disease receiving antipsychotic treatment should be carefully monitored for the development of DM. PMID:26061313

  11. 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. PMID:24106716

  12. 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.

  13. 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.

  14. Familiar Music as an Enhancer of Self-Consciousness in Patients with Alzheimer's Disease

    PubMed Central

    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. PMID:24106716

  15. [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.

  16. Impairment of vocal expression of negative emotions in patients with Alzheimer's disease.

    PubMed

    Han, Kyung-Hun; Zaytseva, Yuliya; Bao, Yan; Pöppel, Ernst; Chung, Sun Yong; Kim, Jong Woo; Kim, Hyun Taek

    2014-01-01

    Vocal expression of emotions (EE) in retrieval of events from autobiographical memory was investigated in patients in early stages of Alzheimer's disease (AD). Twenty-one AD patients and 19 controls were interviewed, and EE of the reported memories was rated by 8 independent evaluators. The AD group had lower EE of both recent and remote memory than controls, although EE in remote memories was better preserved in both groups. We observed positive correlations between EE and indicators of cognitive competence in AD patients. AD Patients are impaired in the ability to express emotions already at early stages of the disease, and EE seems to deteriorate along with the progression of cognitive impairment.

  17. Metamemory in Alzheimer's disease.

    PubMed

    Souchay, Céline

    2007-10-01

    Alois Alzheimer's first publication describes his patient's inability to be aware of her condition. One hundred years later, whether or not Alzheimer's disease (AD) patients show impaired awareness of their memory deficits is still of debate. This review makes a novel contribution, arguing that the ideal empirical tool to assess this question is the metamemory framework. The fact that the metamemory framework offers models of healthy memory and metamemory function and ready-developed measures mapped onto theoretical constructs, means that it is a useful paradigm to explore the question of memory awareness. The review focuses on two as yet separate approaches: the neuropsychological models of anosognosia as well as the metamemory framework. Metamemory constructs and measures are used to evaluate Alzheimer's patients' awareness of their memory difficulties by relating the main findings to the existing neuropsychological model of anosognosia. With this approach, only very specific deficits in awareness are found: a failure to update self-beliefs, and a deficit in monitoring episodic memory, possibly related to a deficit in effortful, conscious control processes. This review also considers how the exploration of the neural correlates of metamemory can help to draw novel hypotheses on the brain regions implicated in anosognosia in AD.

  18. Similar deficits of central histaminergic system in patients with Down syndrome and Alzheimer disease.

    PubMed

    Schneider, C; Risser, D; Kirchner, L; Kitzmüller, E; Cairns, N; Prast, H; Singewald, N; Lubec, G

    1997-02-01

    In order to study whether Alzheimer-like neuropathological changes involve the central histaminergic system we measured the concentration of histamine, its precursor histidine as well as the activity of histidine decarboxylase (HDC) and histamine-N-methyl-transferase (HMT) in frontal cortex of aging Down syndrome (DS) patients, Alzheimer patients and control individuals. The study populations were also investigated for choline acetyltransferase (ChAT) activity, since reduced ChAT activity is an established biochemical hallmark in DS and Alzheimer disease (AD). HDC and ChAT activity were reduced in brains of both DS and Alzheimer patients versus control patients. Additionally, we observed a significant decrease of histamine levels in the DS group. Histamine levels in AD brains tended to be decreased. Histidine concentrations and HMT activities were comparable between the three groups. Thus, our results for the first time show histaminergic deficits in brains of patients with DS resembling the neurochemical pattern in AD. Neuropathological changes may be responsible for similar neurochemical alterations of the histaminergic system in both dementing disorders.

  19. The Effect of Lipoic Acid Therapy on Cognitive Functioning in Patients with Alzheimer's Disease

    PubMed Central

    Fava, Antonietta; Pirritano, Domenico; Plastino, Massimiliano; Cristiano, Dario; Puccio, Giovanna; Colica, Carmen; Ermio, Caterina; De Bartolo, Matteo; Mauro, Gaetano

    2013-01-01

    Diabetes mellitus (DM) is an important risk factor for Alzheimer's disease (AD). Most diabetic patients have insulin resistance (IR) that is associated with compensatory hyperinsulinemia, one of the mechanisms suggested for increased AD risk in patients with DM. Alpha-lipoic acid (ALA) is a disulfide molecule with antioxidant properties that has positive effects on glucose metabolism and IR. This study evaluated the effect of ALA treatment (600 mg/day) on cognitive performances in AD patients with and without DM. One hundred and twenty-six patients with AD were divided into two groups, according to DM presence (group A) or absence (group B). Cognitive functions were assessed by MMSE, Alzheimer's Disease Assessment Scale-cognitive (ADAS-Cog), Clinician's Interview-Based Impression of Severity (CIBIC), Clinical Dementia Rating (CDR), and Alzheimer's Disease Functional and Change Scale (ADFACS). IR was assessed by HOMA index. At the end of the study, MMSE scores showed a significant improvement in 43% patients of group A (26 subjects) and 23% of group B (15 subjects), compared to baseline (P = .001). Also ADAS-Cog, CIBIC, and ADFACS scores showed a significant improvement in group A versus group B. IR was higher in group A. Our study suggests that ALA therapy could be effective in slowing cognitive decline in patients with AD and IR. PMID:26316990

  20. Microprobe PIXE analysis of aluminium in the brains of patients with Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Yumoto, S.; Horino, Y.; Mokuno, Y.; Kakimi, S.; Fujii, K.

    1996-04-01

    To investigate the cause of Alzheimer's disease (senile dementia), we examined aluminium (Al) in the rat liver, and in the brains (hippocampus) of Alzheimer's disease patients using heavy ion (5 MeV Si 3+) microprobe and proton (2 MeV) microprobe PIXE analysis. Heavy ion microprobes (3 MeV Si 2+) have several time's higher sensitivity for Al detection than 2 MeV proton microprobes. (1) In the rat liver, Al was detected in the cell nuclei, where phosphorus (P) was most densely distributed. (2) We also demonstrated Al in the cell nuclei isolated from Alzheimer's disease brains using heavy ion (5 MeV Si 3+) microprobes. Al spectra were detected using 2 MeV proton microprobes in the isolated brain cell nuclei. Al could not be observed in areas where P was present in relatively small amounts, or was absent. Our results indicate that Alzheimer's disease is caused by irreversible accumulation of Al in the nuclei of brain cells.

  1. Drug treatment of Alzheimer's disease. Effects on caregiver burden and patient quality of life.

    PubMed

    Hollister, L; Gruber, N

    1996-01-01

    Alzheimer's disease is a devastating illness that will become more common as the population ages. Although clinical diagnosis of the illness is not certain without histological examination of the brain, and misdiagnosis may occur, broad working criteria to help diagnose the likely presence of Alzheimer's disease are available. Thoughtful clinical evaluation improves diagnostic accuracy, and appropriately diagnosed patients are critical for involvement in research into new antidementia agents. Essential to the discovery of new drugs is careful measurement of illness response. A variety of scales--some aimed at patients, others at their caregivers, and yet others for clinicians--assess Alzheimer's disease severity, progression, symptom response, and quality of life. Of note, patient response is not the only measurement of treatment benefit today. Growing interest is also being placed on tracking the possible amelioration of caregiver 'burden'. This burden refers to the psychological, physical, and material costs of providing care for an Alzheimer's patient over long periods of time. A number of scales and questionnaires have been developed and are occasionally used. Many drugs have been tried in Alzheimer's disease, but very few have produced any benefit, and this is often modest. Ergoloid mesylates, initially thought to be effective, are now considered of little value. The cholinomimetic drugs, especially the acetylcholinesterase inhibitor tacrine, have provided a very modest benefit, slowing the progression of the illness for a number of months. No cognitive improvement has been noted with the various nootropic agents such as piracetam. Early studies with levacecarnine (acetyl-L-carnitine), a substance that facilitates the use of fatty acids, memantidine, the dimethyl derivative of amantidine, and the calcium channel blocker nimodipine, have shown some promise, but require larger, more rigorous studies. As mentioned above, documenting effects in individual patients

  2. First episodes of behavioral symptoms in Alzheimer's disease patients at age 90 and over, and early-onset Alzheimer's disease: comparison with senile dementia of Alzheimer's type.

    PubMed

    Hori, Koji; Oda, Tatsuro; Asaoka, Toshiyasu; Yoshida, Masahiro; Watanabe, Shoichi; Oyamada, Reiko; Tominaga, Itaru; Inada, Toshiya

    2005-12-01

    We evaluated dementia symptoms to clarify the character of dementia with Alzheimer's disease (AD) observed in the oldest old patients and that of dementia with early-onset AD. Subjects were consecutive AD inpatients admitted for the first time at age of 90 years and over because of behavioral symptoms (demented nonagenarian group: D90G; n=18) and those with 24 consecutive inpatients with AD with early-onset (EOG). The Gottfries, Brane and Steen's scale and the Dementia Behavior Disturbance scale were used to evaluate the symptoms and troublesome behaviors. The scores of these scales in D90G and in EOG were compared with those of 26 sex distribution-, severity of dementia-, and disease duration-matched inpatients with AD with late-onset (LOG). Compared with LOG, wakefulness was more impaired and waking up at night was more frequent in D90G, while memory, orientation and inappropriate behaviors were more severe in EOG. These results suggest that the clinical features of dementia in EOG were quantitatively different from those of LOG. In contrast, the clinical feature of dementia of D90G were sleep-wake pattern disturbance and were qualitatively different from those of LOG. PMID:16401251

  3. 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.

  4. Seizures in Alzheimer's disease.

    PubMed

    Born, H A

    2015-02-12

    Alzheimer's disease (AD) increases the risk for late-onset seizures and neuronal network abnormalities. An elevated co-occurrence of AD and seizures has been established in the more prevalent sporadic form of AD. Recent evidence suggests that nonconvulsive network abnormalities, including seizures and other electroencephalographic abnormalities, may be more commonly found in patients than previously thought. Patients with familial AD are at an even greater risk for seizures, which have been found in patients with mutations in PSEN1, PSEN2, or APP, as well as with APP duplication. This review also provides an overview of seizure and electroencephalography studies in AD mouse models. The amyloid-β (Aβ) peptide has been identified as a possible link between AD and seizures, and while Aβ is known to affect neuronal activity, the full-length amyloid precursor protein (APP) and other APP cleavage products may be important for the development and maintenance of cortical network hyperexcitability. Nonconvulsive epileptiform activity, such as seizures or network abnormalities that are shorter in duration but may occur with higher frequency, may contribute to cognitive impairments characteristic of AD, such as amnestic wandering. Finally, the review discusses recent studies using antiepileptic drugs to rescue cognitive deficits in AD mouse models and human patients. Understanding the mechanistic link between epileptiform activity and AD is a research area of growing interest. Further understanding of the connection between neuronal hyperexcitability and Alzheimer's as well as the potential role of epileptiform activity in the progression of AD will be beneficial for improving treatment strategies.

  5. Emotional Memory in Patients with Alzheimer's Disease: A Report of Two Cases

    PubMed Central

    Okada, Akira; Matsuo, Junko

    2012-01-01

    Highly emotional events in daily life can be preserved in memory and such memory is generally referred to as emotional memory. Some reports have demonstrated that emotional memory is also found in patients with Alzheimer's disease (AD). However, to our knowledge, there have been no reports about how long memory retention for emotional events can continue in patients with AD. In this paper, we present two patients with AD who lost an immediate family member during followup and retained the memory over a long period despite progression of the AD. PMID:22934217

  6. Bingo vs. physical intervention in stimulating short-term cognition in Alzheimer's disease patients.

    PubMed

    Sobel, B P

    2001-01-01

    Past research has shown that pharmacological measures can enhance cognitive and functional capacities for patients with Alzheimer's disease, but may result in unacceptable side effects. Investigations using nonpharmacological treatments are limited. This study evaluates the therapeutic effect of the game of Bingo as cognitive stimulation, versus daily physical activity, on short-term memory, concentration, word retrieval, and word recognition. Informed consent was obtained from the designated representatives of 50 subjects from six community adult day care centers on Long Island. The results show that cognitive stimulation enhanced performance on the Boston Naming Test and a Word List Recognition Task; physical intervention, however, did not reach statistical significance. Thus, a simple cognitive activity such as Bingo can be of great value to the daily management of Alzheimer's patients.

  7. Progressive cholinergic decline in Alzheimer's Disease: consideration for treatment with donepezil 23 mg in patients with moderate to severe symptomatology.

    PubMed

    Sabbagh, Marwan; Cummings, Jeffrey

    2011-02-07

    Of the estimated 5.3 million people with Alzheimer's disease in the United States, more than half would be classified as having moderate or severe disease. Alzheimer's disease is a progressive disorder with the moderate to severe stages generally characterized by significant cognitive, functional, and behavioral dysfunction. Unsurprisingly, these advanced stages are often the most challenging for both patients and their caregivers/families. Symptomatic treatments for moderate to severe Alzheimer's disease are approved in the United States and include the acetylcholinesterase inhibitor donepezil and the glutamate receptor antagonist memantine. Progressive symptomatic decline is nevertheless inevitable even with the available therapies, and therefore additional treatment options are urgently needed for this segment of the Alzheimer's disease population. An immediate-release formulation of donepezil has been available at an approved dose of 5-10 mg/d for the past decade. Recently, the United States Food and Drug Administration approved a higher-dose (23 mg/d) donepezil formulation, which provides more gradual systemic absorption, a longer time to maximum concentration (8 hours) versus the immediate-release formulation (3 hours), and higher daily concentrations. Herein, we review (1) the scientific data on the importance of cholinergic deficits in Alzheimer's disease treatment strategies, (2) the rationale for the use of higher-dose acetylcholinesterase inhibitors in patients with advanced disease, and (3) recent clinical evidence supporting the use of higher-dose donepezil in patients with moderate to severe Alzheimer's disease.

  8. 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

  9. 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

  10. 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…

  11. [Support for patients with Alzheimer's disease and their caregivers by gerontechnology].

    PubMed

    Rigaud, Anne-Sophie; Pino, Maribel; Wu, Ya-Huei; DE Rotrou, Jocelyne; Boulay, Melodie; Seux, Marie-Laure; Hugonot-Diener, Laurence; DE Sant'anna, Martha; Moulin, Florence; LE Gouverneur, Gregory; Cristancho-Lacroix, Victoria; Lenoir, Hermine

    2011-03-01

    The increasing number of people suffering from Alzheimer's disease raises the question of their caring at home, especially when the disease causes disability and negative consequences in daily life such as isolation, falls, wandering, errors in drug taking. Furthermore, caregivers bear a substantial burden that can have adverse effects on their physical and mental health. New technologies of information could play an additional role as care providers without substituting family or professional caregivers help. A review of literature focused on the different technological solutions conceived for patients suffering from Alzheimer's disease and their carers shows that these appliances could help to provide reminders in daily life (drugs, tasks and appointments, meals cooking), to activate residual cognitive resources by computerized cognitive stimulation intervention, to reduce stress, anxiety and depressive symptoms in patients by visual contact with families and professionals (webconference), to contribute to patients safety by detecting falls and wandering, and to help families in the caring of patients with computerized information and counselling interventions. We also discuss the current limitations for a widespread use of these technologies and outline future research avenues. True needs of end-users are still poorly known and should be more clearly defined. Simplicity of the use of these appliances should be further improved. Demonstration of medical and social benefits for elderly people should be carried out in randomized, controlled studies. Ethical reflexion should be developed in conjunction with the use of these gerontechnologies. Finally, the economical model which would enable the providing of these appliances to the largest number of patients and caregivers should be implemented. Although these gerontechnologies are promising, research is still needed to tailor them properly to the needs of end-users, assess their benefit in ecological context of

  12. [Alzheimer's disease and olfaction].

    PubMed

    Naudin, Marine; Mondon, Karl; Atanasova, Boriana

    2013-09-01

    Although olfactory disorders are not at the forefront of the clinical description of Alzheimer's disease (AD), they are common and often overlooked by clinicians and by patients who are largely unaware of their deficits. The past 30 years, the literature has shown early olfactory deficits in AD that is spreading across the olfactory spectrum with disease worsening. Partial overlap between brain areas implies both in olfaction and AD - especially limbic system - motivating these researches. This study describes olfactory parameters and tests using to investigate peripheral (odor threshold) and central (hedonicity, familiarity, intensity, discrimination, identification, olfactory memory) levels. Besides, this article takes an inventory of olfactory disorders in AD including odor threshold, discrimination, identification and olfactory memory capacities with controversial results observed in literature. At last, we discuss which type of olfactory dysfunction could have a clinical interest.

  13. 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.

  14. Characteristics of lymphocyte chromatin from Alzheimer's disease patients and from young and old normal individuals.

    PubMed

    Smith, T A; Vallis, Y; Neary, D; Itzhaki, R F

    1989-01-01

    We have examined chromatin in lymphocytes from patients with Alzheimer's disease (AD) and from normal individuals of a range of ages. We have found that the neucleosome repeat length does not vary with age for normal individuals over the range 24-78 years and that there is no difference between the value for AD cells (mean and standard deviation, 202 +/- 7 base pairs, bp) and for normals (207 +/- 5 bp). The rate of digestion of chromatin in lymphocyte nuclei by micrococcal nuclease does not appear to differ significantly between old and young normals and AD patients.

  15. 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. PMID:9672379

  16. Relatives' attitudes towards informing patients about the diagnosis of Alzheimer's disease

    PubMed Central

    Pucci, E; Belardinelli, N; Borsetti, G; Giuliani, G

    2003-01-01

    Objectives: To evaluate relatives' attitudes towards informing patients with Alzheimer's disease (AD) about their diagnosis. Setting: A university hospital in Italy. Methods: The closest relatives of each of 71 subjects diagnosed for the first time as having AD were interviewed, using a semistructured questionnaire. Spontaneous requests by relatives not to communicate issues concerning the diagnosis were also recorded. Results: Forty three (60.6%) relatives spontaneously requested that patients not be fully informed. After being interviewed, nobody thought that the patient should be given all the information. Justifications were related to the fear of the onset or worsening of depressive symptoms in the patient. Conclusions: In Italy relatives' opposition to informing AD patients appears to be common. Knowledge of the relatives' attitudes may be useful for clinicians but disclosure of diagnosis should be based on the clinical evaluation of the patient and on a prudent evaluation of the relationship between the patient and her/his relative caregiver. PMID:12569197

  17. Dementia: Depression and Alzheimer's Disease

    MedlinePlus

    MENU Return to Web version Dementia | Depression and Alzheimer’s Disease What is depression? When doctors talk about ... time Thoughts about death or suicide What is Alzheimer's disease? Alzheimer's disease is the most common type ...

  18. Progress in Alzheimer's disease.

    PubMed

    Galimberti, Daniela; Scarpini, Elio

    2012-02-01

    After more than one century from Alois Alzheimer and Gaetano Perusini's first report, progress has been made in understanding the pathogenic steps of Alzheimer's disease (AD), as well as in its early diagnosis. This review discusses recent findings leading to the formulation of novel criteria for diagnosis of the disease even in a preclinical phase, by using biological markers. In addition, treatment options will be discussed, with emphasis on new disease-modifying compounds and future trial design suitable to test these drugs in an early phase of the disease.

  19. 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.

  20. 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. PMID:25792098

  1. 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.

  2. Impairment of vocal expression of negative emotions in patients with Alzheimer's disease.

    PubMed

    Han, Kyung-Hun; Zaytseva, Yuliya; Bao, Yan; Pöppel, Ernst; Chung, Sun Yong; Kim, Jong Woo; Kim, Hyun Taek

    2014-01-01

    Vocal expression of emotions (EE) in retrieval of events from autobiographical memory was investigated in patients in early stages of Alzheimer's disease (AD). Twenty-one AD patients and 19 controls were interviewed, and EE of the reported memories was rated by 8 independent evaluators. The AD group had lower EE of both recent and remote memory than controls, although EE in remote memories was better preserved in both groups. We observed positive correlations between EE and indicators of cognitive competence in AD patients. AD Patients are impaired in the ability to express emotions already at early stages of the disease, and EE seems to deteriorate along with the progression of cognitive impairment. PMID:24904413

  3. Spontaneous and induced chromosome damage in somatic cells of sporadic and familial Alzheimer's disease patients.

    PubMed

    Trippi, F; Botto, N; Scarpato, R; Petrozzi, L; Bonuccelli, U; Latorraca, S; Sorbi, S; Migliore, L

    2001-07-01

    Alzheimer's disease (AD) is a neurodegenerative disorder of the elderly with a complex etiology due to the interaction between genetic and environmental factors. At least 15% of cases are inherited as an autosomal dominant mutation, but the majority are sporadic. We evaluated cytogenetic alterations, both spontaneous and chemical-induced [aluminium (Al) and griseofulvin (GF)], by means of the micronucleus (MN) test in lymphocytes or skin fibroblasts of 14 patients with sporadic and eight with familial Alzheimer's disease (FAD), respectively. The spontaneous MN frequencies of sporadic (20.8 +/- 9.2) and familial (20.7 +/- 4.6) AD patients are significantly higher than those of the respective control groups (9.0 +/- 6.8 and 6.7 +/- 3.4). In all AD patients, GF significantly increased the spontaneous MN frequency of somatic cells to a lesser extent (P < 0.05) as compared with the control group. Al treatment did not induce MN in AD patients. The results of the present study indicate that different types of somatic cells from sporadic and familial AD patients show comparable levels of spontaneous cytogenetic anomalies, and MN induction is partially reduced or lacking according to the type of chemical treatments. PMID:11420400

  4. Anosognosia: patients' distress and self-awareness of deficits in Alzheimer's disease.

    PubMed

    Maki, Yohko; Amari, Masakuni; Yamaguchi, Tomoharu; Nakaaki, Shutaro; Yamaguchi, Haruyasu

    2012-08-01

    We aimed to study how patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) suffer from awareness of their deficits. Self-awareness was assessed using the Anosognosia Questionnaire for Dementia in 12 pairs of MCI outpatients and caregivers, 23 with mild AD, and 18 with moderate AD. The discrepancy between patient's and caregiver's evaluation (anosognosia) became greater as AD progressed. The predictors of patients' distress, shown by multiple linear regression analyses, were awareness of decline in intellectual or social functioning; self-awareness of deficits in remembering appointments in MCI; in remembering appointments, writing, mental calculation, and understanding the newspaper in mild AD; and in mental calculation and doing clerical work in moderate AD. Caregivers assumed the predictors of patients' distress differently: awareness of deterioration of memory in MCI and mild AD, and basic activities of daily living in moderate AD. Understanding patients' disability from patients' perspective is required for successful care.

  5. Diagnostic Assessment and Management of Dysphagia in Patients with Alzheimer's Disease.

    PubMed

    Boccardi, Virginia; Ruggiero, Carmelinda; Patriti, Alberto; Marano, Luigi

    2016-01-01

    A growing concern in patients affected by Alzheimer's disease (AD) is dysphagia, or swallowing impairment, which leads to malnutrition, dehydration, weight loss, functional decline and fear of eating and drinking, as well as a decrease in the quality of life. Thus the diagnostic assessment of dysphagia in patients with AD is imperative to ensure that they receive effective management, avoiding complications, and reducing comorbidity and mortality in such a growing population. Dysphagia management requires a multidisciplinary approach considering that no single strategy is appropriate for all patients. However, evidence for clinical diagnostic assessment, interventions, and medical management of dysphagia in these patients are still limited: few studies are reporting the evaluation and the management among this group of patients. Here we analyzed the most recent findings in diagnostic assessment and management of swallowing impairment in patients affected by AD. PMID:26836016

  6. 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.

  7. Androgen deprivation therapy did not increase the risk of Alzheimer's and Parkinson's disease in patients with prostate cancer.

    PubMed

    Chung, S D; Lin, H C; Tsai, M C; Kao, L T; Huang, C Y; Chen, K C

    2016-05-01

    Androgen deprivation therapy (ADT) has been the standard treatment for advanced prostate cancer for many decades. Although potential adverse effects of ADT have been reported, there are no empirical studies investigating the association between ADT and Alzheimer's disease. Therefore, this retrospective cohort study explored the relationship between the use of ADT and the subsequent risk of Alzheimer's disease in men with prostate cancer using a population-based database. We retrieved data from the "Taiwan Longitudinal Health Insurance Database 2000." The study included 1335 patients with prostate cancer and 4005 age-matched comparison patients without prostate malignancy. We then individually tracked each patient (n = 5340) for a 5-year period to discriminate those who subsequently received a diagnosis of Alzheimer's disease. The Cox proportional hazard regression showed that the hazard ratio (HR) for Alzheimer's disease during the 5-year follow-up period for prostate cancer patients was 1.71 (95% confidence interval (CI) = 0.90~3.25) over that of comparison patients. We further analyzed the hazard ratio for Alzheimer's disease and Parkinson's disease between prostate cancer patients who did and those who did not receive ADT, but we failed to observe a significant difference in the hazard ratio for both diseases during the 5-year follow-up period (adjusted HR = 1.76, 95% CI = 0.55~5.62, and HR = 1.13, 95% CI = 0.58~2.20, respectively). In conclusion, this study demonstrated that the use of androgen deprivation therapy in patients with prostate cancer was not associated with a higher risk of Alzheimer's and Parkinson's disease during the follow-up period. PMID:27062333

  8. Androgen deprivation therapy did not increase the risk of Alzheimer's and Parkinson's disease in patients with prostate cancer.

    PubMed

    Chung, S D; Lin, H C; Tsai, M C; Kao, L T; Huang, C Y; Chen, K C

    2016-05-01

    Androgen deprivation therapy (ADT) has been the standard treatment for advanced prostate cancer for many decades. Although potential adverse effects of ADT have been reported, there are no empirical studies investigating the association between ADT and Alzheimer's disease. Therefore, this retrospective cohort study explored the relationship between the use of ADT and the subsequent risk of Alzheimer's disease in men with prostate cancer using a population-based database. We retrieved data from the "Taiwan Longitudinal Health Insurance Database 2000." The study included 1335 patients with prostate cancer and 4005 age-matched comparison patients without prostate malignancy. We then individually tracked each patient (n = 5340) for a 5-year period to discriminate those who subsequently received a diagnosis of Alzheimer's disease. The Cox proportional hazard regression showed that the hazard ratio (HR) for Alzheimer's disease during the 5-year follow-up period for prostate cancer patients was 1.71 (95% confidence interval (CI) = 0.90~3.25) over that of comparison patients. We further analyzed the hazard ratio for Alzheimer's disease and Parkinson's disease between prostate cancer patients who did and those who did not receive ADT, but we failed to observe a significant difference in the hazard ratio for both diseases during the 5-year follow-up period (adjusted HR = 1.76, 95% CI = 0.55~5.62, and HR = 1.13, 95% CI = 0.58~2.20, respectively). In conclusion, this study demonstrated that the use of androgen deprivation therapy in patients with prostate cancer was not associated with a higher risk of Alzheimer's and Parkinson's disease during the follow-up period.

  9. [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.

  10. [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. PMID:25786430

  11. [Overview on Alzheimer's disease].

    PubMed

    Ihara, Yasuo

    2007-11-01

    It is now one hundred years since the first publication on Alzheimer's disease by Alois Alzheimer. Since 1980's deciphering Alzheimer's disease has greatly quickened, and investigators currently think that it becomes possible to treat or prevent Alzheimer's disease that is the major socioeconomical concern in all the developed countries. We owe this current understanding to three major advances, development of Abeta vaccination and gamma-modifiers, and a series of large-scale prospective studies. J-ADNI is being undertaken from this fall, which follows the protocols by US-ADNI. The major goal is establishment of the surrogate marker for AD based on MRI data. In addition, this project would provide more clarification of MCI and dementia themselves and their differentiation. In view of the temporal profile of Alzheimer disease, it is essential to detect at-risk people who carry senile plaques (amyloid) but are cognitively normal. Even in MCI more than 50% of neurons in layer 2 is already lost. For such very early detection of at-risk people biomaker would be helpful. According to sink hypothesis, there is chemical equilibrium of Abeta between in plasma, CSF and senile plaques. Thus what we should do is to find insoluble Abeta-specific fragments or modifications in the peripheral blood.

  12. Population pharmacokinetic modelling of NS2330 (tesofensine) and its major metabolite in patients with Alzheimer's disease

    PubMed Central

    Lehr, Thorsten; Staab, Alexander; Tillmann, Christiane; Trommeshauser, Dirk; Raschig, Andreas; Schaefer, Hans Guenter; Kloft, Charlotte

    2007-01-01

    What is already known about this subject Several studies in predominantly healthy subjects have investigated the pharmacokinetics of NS2330 and its major metabolite M1. However, its pharmacokinetics have not been characterized in Alzheimer's disease patients, the target population for NS2330. In addition, no covariates have previously been found to influence the plasma concentration-time profiles of NS2330 and/or M1. What this study adds A descriptive and predictive population pharmacokinetic model for NS2330 and its metabolite was successfully developed in a population of patients with Alzheimer's disease. A covariate analysis elucidated sex and creatinine clearance as having an influence on the plasma concentration-time profiles of NS2330 after long-term treatment. Aims To develop a population pharmacokinetic model for NS2330 and its major metabolite M1 based on data from a 14 week proof of concept study in patients with Alzheimer's disease, and to identify covariates that might influence the pharmacokinetic characteristics of the drug and/or its metabolite. Methods Plasma data from 320 subjects undergoing multiple oral dosing, and consisting of 1969 NS2330 and 1714 metabolite concentrations were fitted simultaneously using NONMEM. Results Plasma concentration-time profiles of NS2330 and M1 were best described by one-compartment models with first-order elimination for both compounds. Absorption of NS2330 was best modelled by a first-order process. Low apparent clearances together with large apparent volumes of distribution resulted in long half-lives of 234 h (NS2330) and 374 h (M1). The covariate analysis identified weight, sex, CLCR, BMI and age as influencing the pharmacokinetics of NS2330 and/or M1. However, simulations performed revealed that only CLCR and sex had a significant effect on the steady-state plasma concentration-time profiles. Females with a creatinine clearance of 35.6 ml min−1 showed a 62% increased exposure compared with males without renal

  13. Predictors of mortality in patients with Alzheimer's disease living in nursing homes

    PubMed Central

    Gambassi, G.; Landi, F.; Lapane, K.; Sgadari, A.; Mor, V.; Bernabei, R.

    1999-01-01

    OBJECTIVES—To identify factors associated with mortality in patients with Alzheimer's disease, and to evaluate whether these factors vary according to severity of cognitive impairment.
METHODS—Data were from the SAGE database which includes information on all residents admitted between 1992 and 1995 to all Medicare/ Medicaid certified nursing homes of five US states. We conducted a longitudinal follow up study (median 23 months) on 9264 patients aged 65 years and above with a diagnosis of Alzheimer's disease. Patient data including demographic characteristics, dementia severity, comorbidity, and other clinical and treatment variables were collected with the Minimum Data Set. Information on death was derived through linkage to Medicare files. Baseline characteristics were used to predict survival in univariate and multivariate Cox proportional hazard models.
RESULTS—Overall mortality rate was 50%, with a first year rate of 25.7%. Increased age (risk ratio (RR) 1.83; 95% confidence interval (95% CI) 1.65-2.03, for patients 85+ years), male sex (RR 1.81; 95% CI 1.70-1.94), limitation in physical function (RR 1.45; 95% CI 1.27-1.66), a condition of malnutrition (RR 1.31; 95%CI 1.23-1.39), the presence of pressure ulcers (RR 1.24; 95% CI 1.13-1.36), a diagnosis of diabetes mellitus (RR 1.32; 95% CI 1.21-1.43), and of cardiovascular diseases (RR 1.22; 95% CI 1.14-1.30) were independent predictors of death, regardless of the severity of baseline dementia. Sensory problems (hearing and vision) and urinary incontinence were associated with increased mortality only among patients with less severe dementia. The presence of disruptive behaviour, aphasia, and a diagnosis of Parkinson's disease were not related to survival. African-Americans and other minority groups were less likely to die relative to white people.
CONCLUSIONS—Age, sex, functional limitation, and malnutrition seem to be the strongest predictors of death for patients with Alzheimer's disease in

  14. 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.

  15. Institutional placement for patients with Alzheimer's disease. How to help families with a difficult decision.

    PubMed

    Pfeiffer, E

    1995-01-01

    Family members confronting the difficult decision of whether to place a patient with Alzheimer's disease in an institution find it helpful to have explicit criteria on which to base their decision. Regular incontinence of bladder and bowel, inability of the patient to cooperate in his or her care, inability of the patient to realize that he or she is at home with familiar caregivers, the withdrawal of a paid caregiver, risk to the health of the primary caregiver, and primary caregiver burnout are all grounds for considering institutional placement. Options include assisted living facilities, dementia-specific assisted living facilities, general nursing homes, and nursing homes with dementia-specific care units. Institution-like care can be provided at home, but this is expensive and may be inconvenient and stressful for family members. Hospice care is appropriate at the end of the patients's life.

  16. [Working memory for music in patients with mild cognitive impairment and early stage Alzheimer's disease].

    PubMed

    Kerer, Manuela; Marksteiner, Josef; Hinterhuber, Hartmann; Mazzola, Guerino; Kemmler, Georg; Bliem, Harald R; Weiss, Elisabeth M

    2013-01-01

    A variety of studies demonstrated that some forms of memory for music are spared in dementia, but only few studies have investigated patients with early stages of dementia. In this pilot-study we tested working memory for music in patients with mild cognitive impairment (MCI) and early stage Alzheimer's disease (AD) with a newly created test. The test probed working memory using 7 gradually elongated tone-lines and 6 chords which were each followed by 3 similar items and 1 identical item. The participants of the study, namely 10 patients with MCI, 10 patients with early stage AD and 23 healthy subjects were instructed to select the identical tone-line or chord. Subjects with MCI and early AD showed significantly reduced performance than controls in most of the presented tasks. In recognizing chords MCI- participants surprisingly showed an unimpaired performance. The gradual increase of the impairment during the preclinical phase of AD seems to spare this special ability in MCI.

  17. 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

  18. Gait Disorder in a Cohort of Patients With Mild and Moderate Alzheimer's Disease.

    PubMed

    Castrillo, A; Olmos, L M García; Rodríguez, F; Duarte, J

    2016-05-01

    Gait disturbance results in an increase in the risk of falls in patients with Alzheimer's disease (AD). The falls are events that might be related to an increase in the number of fractures, loss of mobility, being bedridden, early institutionalization, and increased use of medication. Therefore, the reduction in the number of falls is important for the maintenance of the functional independence of the patients as well as for the prevention of sequelae resulting from those events. Alterations in the gait occur very frequently in AD, and the gait disturbance occurs relatively early in the course of the disease. This study has important implications for public health and clinical practice. This study and previous studies have reported that abnormal gait predicts greater risk of falls, dementia, institutionalization, and death. The high prevalence and incidence of abnormal gait and its association with multiple adverse outcomes in older adults require urgent attention. Our results allow us to identify the risk factors. PMID:26395024

  19. [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. PMID:25786429

  20. Epitope map of two polyclonal antibodies that recognize amyloid lesions in patients with Alzheimer's disease.

    PubMed Central

    Ghiso, J; Wisniewski, T; Vidal, R; Rostagno, A; Frangione, B

    1992-01-01

    Two synthetic peptides with sequences identical with those of fragments of the extracellular domain of the Alzheimer's-disease amyloid precursor protein (APP) were used to raise antibodies. SP28 comprises positions 597-624 of the APP695 isoform, whereas SP41 extends towards the N-terminus (amino acids 584-624) and contains the entire SP28 peptide. Using e.l.i.s.a. and inhibition experiments we identified the two beta-turn-containing segments 602-607 and 617-624 as the epitopes recognized by anti-SP41 and anti-SP28 respectively. Both antibodies immunolabelled amyloid lesions in brains from Alzheimer's-disease patients and patients with related disorders, whereas they were unreactive in control brains. However, when probed on immunoblots, anti-SP28 failed to detect full-length APP from baculovirus-infected Sf9 cells, and anti-SP41 reacted weakly compared with other anti-APP antisera. The data suggest that these antibodies are directed to conformational epitopes not existent in the native molecules but present after alternative APP processing. Images Fig. 4. Fig. 5. PMID:1372166

  1. 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.

  2. Health-related quality of life for caregivers of patients with Alzheimer disease.

    PubMed

    Markowitz, Jeffrey S; Gutterman, Elane M; Sadik, Kay; Papadopoulos, George

    2003-01-01

    We investigated the relationship of caregivers' health-related quality of life (HRQOL) to the burden of caring for patients with Alzheimer disease (AD) and resource utilization. Caregiver HRQOL was assessed using the SF-12 Mental and Physical Summary scores. Compared with a normative, age-adjusted sample, the 2477 caregivers had lower mental and physical scores (for the latter, only those <54 years of age). Increased caregiver mental functioning was associated with caregiver support and perceived quality of patient medical care, fewer hours of caregiving, and fewer patient behavioral symptoms. The burden of caregiving has substantial effects on HRQOL. Interventions that improve AD status and reduce caregiving hours have the potential to improve caregivers' HRQOL.

  3. Assessing outcomes in Alzheimer disease.

    PubMed

    Schneider, L S

    2001-08-01

    To gain a better overview of the effectiveness of treatment of patients with Alzheimer disease (AD), areas such as cognition, activities of daily living (ADL), behavior, caregiver burden, quality of life and economics need to be assessed. A number of instruments are available for assessing these domains, many of which are reviewed in this article. These include the cognitive subscale of the Alzheimer's Disease Assessment Scale (the standard instrument for the measurement of efficacy in dementia trials), scales that assess AD patients' abilities to perform ADL (including the Disability Assessment for Dementia scale and the Alzheimer's Disease Cooperative Study-Activities of Daily Living), scales to assess behavioral symptoms in dementia (including the Neuropsychiatric Inventory and the Behavioral Pathology in Alzheimer's Disease Rating Scale), scales for assessing global clinical change, and methods for assessing caregiver time, quality of life and health economics. Each instrument has its own advantages and disadvantages. However, the instruments used need to be selected carefully to provide credible and informative outcome data. PMID:11669509

  4. Participants' Evaluation of Educational/Support Groups for Families of Patients with Alzheimer's Disease and Other Dementias.

    ERIC Educational Resources Information Center

    Glosser, Guila; Wexler, Debra

    1985-01-01

    Participants (N=54) of seven eight-week educational/support groups for relatives of patients with Alzheimer's disease and other dementias evaluated the helpfulness of their group experience. The supportive aspects of the group and the information provided about medical and behavioral management of the patient were most highly rated. (Author/NRB)

  5. 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…

  6. Weight loss and rapid cognitive decline in community-dwelling patients with Alzheimer's disease.

    PubMed

    Soto, Maria E; Secher, Marion; Gillette-Guyonnet, Sophie; Abellan van Kan, Gabor; Andrieu, Sandrine; Nourhashemi, Fati; Rolland, Yves; Vellas, Bruno

    2012-01-01

    Weight loss is a frequent complication of Alzheimer's disease (AD) and a strong predictor of adverse outcomes in patients suffering from this disease. The aim of this study was to determine whether weight loss was a predictor of rapid cognitive decline (RCD) in AD. Four hundred fourteen community-dwelling ambulatory patients with a diagnosis of probable AD and a Mini-Mental State Examination (MMSE) score between 10 and 26 from the REAL.FR (REseau sur la maladie d'ALzheimer FRançais) cohort were studied and followed up during 4 years. Patients were classified in 2 groups according to weight loss defined by a loss of 4% or more during the first year of follow-up. RCD was defined as the loss of 3 points or more in MMSE over 6 months. The incidence of RCD was determined among both groups over the last 3 years of follow-up. MMSE, Katz's Activity of Daily Living scale, Mini-Nutritional Assessment scale, co-morbidities, behavioral and psychological symptoms of dementia, medication, level of education, living arrangement, and caregiver's burden were assessed every 6 months. Eighty-seven patients (21.0%) lost 4% or more of their initial weight during the first year. The incidence of RCD for all patients was 57.6 (95% confidence interval (CI) = 51.6-64.8) per 100 person-year (median follow-up of 15.1 months). In Cox proportional hazards models, after controlling for potential confounders, weight loss was a significant predictor factor of RCD (adjusted hazard ratio (HR) = 1.50, 95% CI = 1.04-2.17). In conclusion, weight loss predicted RCD in this cohort. Whether the prevention of weight loss (by improving nutritional status) impacts cognitive decline remains an open question.

  7. [Acceptance of memory impairment and satisfaction with life in patients with mild to moderate Alzheimer's disease].

    PubMed

    Morioka, Mizuho; Tanaka, Makoto; Matsubayashi, Kozo; Kita, Toru

    2004-09-01

    In this study, we focused on acceptance of memory impairment and satisfaction with life in patients with mild to moderate Alzheimer's disease (AD). We interviewed 71 consecutive patients with AD and asked (1) whether they had memory loss, (2) whether they found trouble in life, and (3) how their daily life was. We categorized the patients into three groups based on awareness of memory loss and reference to the cause of memory loss. Cognitive functions were lower in patients who were not aware of memory loss. The rate of satisfaction with life was the highest in patients who were not aware of memory loss, and was the lowest in patients who complained of memory loss with reference to the cause of memory loss, indicating that patients could hardly accept their lives when memory impairment was a serious issue. However, in these patients, depression scores were not high, suggesting that they may somehow adapt themselves to their current status by defining the reason for memory loss. In patients who complained of memory impairment but did not refer to the cause of memory loss, there was a variation in awareness of memory loss and satisfaction with life. The present study indicated that we have to provide individual care and support for AD patients considering their level of acceptance of memory impairment.

  8. [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.

  9. 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. PMID:26071443

  10. 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.

  11. Down Syndrome and Alzheimer's Disease

    MedlinePlus

    ... A A A Share Plus on Google Plus Alzheimer's & Dementia alz.org | IHaveAlz Overview What Is Dementia ... chapter Join our online community Down Syndrome and Alzheimer's Disease As they age, those affected by Down ...

  12. Contribution of non-reference alleles in mtDNA of Alzheimer's disease patients.

    PubMed

    Casoli, Tiziana; Di Stefano, Giuseppina; Spazzafumo, Liana; Balietti, Marta; Giorgetti, Belinda; Giuli, Cinzia; Postacchini, Demetrio; Fattoretti, Patrizia; Conti, Fiorenzo

    2014-04-01

    Many observations suggest that mutations of mitochondrial DNA (mtDNA) could be responsible for the neurodegenerative changes of Alzheimer's disease (AD). Here we examined the signal intensity of the four alleles of each mtDNA nucleotide position (np) in whole blood of AD patients and age-matched controls using MitoChip v2.0 array. Our analysis identified 270 significantly different nps which, with one exception, showed an increased contribution of non-reference alleles in AD patients. Principal component analysis (PCA) and cluster analysis showed that five of these nps could discriminate AD from control subjects with 80% of cases correctly classified. Our data support the hypothesis of mtDNA alterations as an important factor in the etiology of AD. PMID:25590040

  13. Inferring design: evidence of a preference for teleological explanations in patients with Alzheimer's disease.

    PubMed

    Lombrozo, Tania; Kelemen, Deborah; Zaitchik, Deborah

    2007-11-01

    Unlike educated adults, young children demonstrate a "promiscuous" tendency to explain objects and phenomena by reference to functions, endorsing what are called teleological explanations. This tendency becomes more selective as children acquire increasingly coherent beliefs about causal mechanisms, but it is unknown whether a widespread preference for teleology is ever truly outgrown. The study reported here investigated this question by examining explanatory judgments in patients with Alzheimer's disease (AD), whose dementia affects the rich causal beliefs adults typically consult in evaluating explanations. The results indicate that unlike healthy adults, AD patients systematically and promiscuously prefer teleological explanations, suggesting that an underlying tendency to construe the world in terms of functions persists throughout life. This finding has broad relevance not only to understanding conceptual impairments in AD, but also to theories of development, learning, and conceptual change. Moreover, this finding sheds light on the intuitive appeal of creationism. PMID:17958715

  14. 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.

  15. 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%.

  16. Effects of repetitive work on maintaining function in Alzheimer's disease patients.

    PubMed

    Burns, Theressa; McCarten, J Riley; Adler, Geri; Bauer, Mary; Kuskowski, Michael A

    2004-01-01

    The effects of repetitive work on Alzheimer's disease (AD) patient functioning were examined when nine veterans were moved from a work program to a traditional adult day care program. Subjects were reassessed four months after the move with the Mini-Mental State Examination (MMSE), Cognitive Performance Test (CPT), and Geriatric Depression Scale (GDS). Individual slopes were calculated for seven subjects who had longitudinal scores, and expected scores were predicted based on the rate of decline. Observed scores at reassessment were significantly lower than expected scores. The MMSE was on average 4.9 points lower, and the CPT .64 points lower than expected. The GDS did not change. The spouses of all nine patients reported declines in daily living activities. Compared to traditional day care activities, work activities involve sequencing skills and practice may translate to self-care activities at home.

  17. 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.

  18. The use of fiber tractography for identifying patients with Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Dong, Kyung-Rae; Goo, Eun-Hoe; Lee, Jae-Seung; Chung, Woon-Kwan

    2013-01-01

    This study examined the usefulness of fiber tractography (FT) for identifying patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) through diffusion tensor imaging (DTI). DTI was performed on twelve patients with AD (four males and eight females, mean age: 78.1 ± 7.5 years) and an eleven patients with MCI (five males and six females, mean age: 69.3 ± 8.0 years) from January to December 2011 by using a 3.0T scanner. Two regions of interest were drawn on the pyramidal tract of Pons and the posterior limb of the internal capsule, which passed through both cortico spinal tracts on the color-cored fractional anisotropy (FA) map. The numbers of white matter fibers on the DTIs in the patients with AD and MCI were determined. The numbers of white matter fibers in the AD patients were 1055.67 ± 333.12 and 860.75 ± 355.50 on the left and the right, respectively. In the patients with MCI, the numbers of white matter fibers and were 1329.82 ± 238.99 and 1316.55 ± 215.25 on the left and the right, respectively. The difference between the right and the left sides in the AD patients was slightly higher than that in the MCI patients.

  19. Adrenergic Drugs Blockers or Enhancers for Cognitive Decline ? What to Choose for Alzheimer's Disease Patients?

    PubMed

    Femminella, Grazia D; Leosco, Dario; Ferrara, Nicola; Rengo, Giuseppe

    2016-01-01

    The adrenergic system has an important role in normal central nervous system function as well as in brain disease. The locus coeruleus, the main source of norepinephrine in brain, is involved in the regulation of learning and memory, reinforcement of sleep-wake cycle and synaptic plasticity. In Alzheimer's disease, locus coeruleus degeneration is observed early in the course of the disease, years before the onset of clinical cognitive signs, with neurofibrillary detected at the stage of mild cognitive impairment, preceding amyloid deposition. Thus, in the last years, a great interest has grown in evaluating the possibility of central adrenergic system modulation as a therapeutic tool in Alzheimer's disease. However, evidences do not show univocal results, with some studies suggesting that adrenergic stimulation might be beneficial in Alzheimer's Disease and some others favoring adrenergic blockade. In this review, we summarize data from both hypothesis and describe the pathophysiological role of the adrenergic system in neurodegeneration. PMID:27189470

  20. 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. PMID:18317250

  1. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials

    PubMed Central

    Rollin-Sillaire, Adeline; Breuilh, Laetitia; Salleron, Julia; Bombois, Stéphanie; Cassagnaud, Pascaline; Deramecourt, Vincent; Mackowiak, Marie-Anne; Pasquier, Florence

    2013-01-01

    Aim To assess reasons that prevent Alzheimer's disease (AD) patients from being included in clinical trials. Methods In 2009, we reviewed the Lille Memory Clinic's case database to identify patients suitable for inclusion in four AD clinical trials. An initial selection was made on the basis of four criteria: (i) a diagnosis of AD (with or without white matter lesions [WML]), (ii) age, (iii) mini mental state examination (MMSE) score and (iv) symptomatic treatment of AD (cholinesterase inhibitors/memantine). Next, data on patients fulfilling these criteria were reviewed against all the inclusion/exclusion criteria for four clinical trials performed in 2009 at the Memory Clinic. Reasons for non-inclusion were analyzed. Results Two hundred and five patients were selected according to the four initial criteria. Reasons for subsequently not including some of patients in clinical trials were abnormalities on MRI (56.9%, 88.9% of which were WML), unauthorized medication (37.3%), the lack of a study partner/informant (37.1%), the presence of a non-authorized disease (24.4%), contraindication to MRI (9%), a change in diagnosis over time (3.9%), visual/auditory impairments (2.9%), alcohol abuse (2%) and an insufficient educational level (1%). Conclusion A high proportion of AD patients presented with vascular abnormalities on MRI. This was not unexpected, since the patients were selected from the database and, as shown in epidemiologic studies, cerebrovascular diseases are frequently associated with AD. The presence of a study partner is essential for enabling a patient to participate in clinical trials because of the need to record reliably primary and secondary outcomes. PMID:22891847

  2. Alzheimer's disease in the United Kingdom: developing patient and carer support strategies to encourage care in the community.

    PubMed Central

    Hunter, R; McGill, L; Bosanquet, N; Johnson, N

    1997-01-01

    Alzheimer's disease is a growing challenge for care providers and purchasers. With the shift away from the provision of long term institutional care in most developed countries, there is a growing tendency for patients with Alzheimer's disease to be cared for at home. In the United Kingdom, this change of direction contrasts with the policies of the 1980s and 90s which focused more attention on controlling costs than on assessment of the needs of the patient and carer and patient management. In recent years, the resources available for management of Alzheimer's disease have focused on institutional care, coupled with drug treatment to control difficult behaviour as the disease progresses. For these reasons, the current system has led to crisis management rather than preventive support--that is, long term care for a few rather than assistance in the home before the crises occur and institutional care is needed. Despite recent innovations in the care of patients with Alzheimer's disease, the nature of the support that patients and carers receive is poorly defined and sometimes inadequate. As a result of the shift towards care in the community, the informal carer occupies an increasingly central role in the care of these patients and the issue of how the best quality of care may be defined and delivered is an issue which is now ripe for review. The objective of this paper is to redefine the type of support that patients and carers should receive so that the disease can be managed more effectively in the community. The needs of patients with Alzheimer's disease and their carers are many and this should be taken into account in defining the quality and structure of healthcare support. This paper shows how new initiatives, combined with recently available symptomatic drug treatment, can allow patients with Alzheimer's disease to be maintained at home for longer. This will have the dual impact of raising the quality of care for patients and improving the quality of life

  3. Gluthatione level is altered in lymphoblasts from patients with familial Alzheimer's disease.

    PubMed

    Cecchi, C; Latorraca, S; Sorbi, S; Iantomasi, T; Favilli, F; Vincenzini, M T; Liguri, G

    1999-11-12

    Intracellular levels of glutathione (GSH), glutathione disulphide (GSSG), glutamic acid and gamma-glutamyl cysteine synthetase (gamma-GCS) were measured in lymphoblast lines from patients with familial and sporadic Alzheimer's disease (AD) and from age-matched controls. Lymphoblasts carrying presenilins (PS) and amyloid precursor protein (APP) genes mutations showed significantly decreased GSH content with respect to controls. Levels of GSSG and glutamic acid, as well as the activity of gamma-GCS were not significantly different in lymphoblasts carrying genes mutations as compared with control cells. These results indicate that even peripheral cells not involved in the neurodegenerative process of AD show altered GSH content when carrying PS and APP genes mutations. The provided data appear to be in accordance with the known alteration of GSH levels in central nervous system and strengthen the hypothesis of oxidative stress as an important, possibly crucial mechanism in the pathogenesis of AD. PMID:10568522

  4. Elevated levels of oxidative DNA damage in lymphocytes from patients with Alzheimer's disease.

    PubMed

    Mórocz, Mónika; Kálmán, János; Juhász, Anna; Sinkó, Ildikó; McGlynn, Angela P; Downes, C Stephen; Janka, Zoltán; Raskó, István

    2002-01-01

    Previous studies have provided evidence of the involvement of oxidative damage in the pathogenesis of Alzheimer's disease (AD). Although the role of oxidative stress in the aetiology of the disease is still not clear, the detection of an increased damage status in the cells of patients could have important therapeutic implications. The level of oxidative damage and repair capacity in peripheral lymphocytes of AD patients and of age-matched controls was determined by the Comet assay applied to freshly isolated blood samples with oxidative lesion-specific DNA repair endonucleases. This is less prone to errors arising from oxidative artifacts than chemical analytical methods; and is therefore a relatively reliable, as well as rapid method for assay of oxidative DNA damage in cells. Statistically significant elevations (P < 0.05) of oxidized purines were observed in nuclear DNA of peripheral lymphocytes from AD patients, compared to age matched control subjects, both at basal level and after oxidative stress induced by H(2)O(2.) AD patients also showed a diminished repair of H(2)O(2) -induced oxidized purines.

  5. 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

  6. Word-stem completion task to investigate semantic network in patients with Alzheimer's disease.

    PubMed

    Passafiume, D; Di Giacomo, D; Carolei, A

    2006-05-01

    Semantic impairment in patients with Alzheimer's disease (AD) is revealed by tasks of verbal naming, verbal fluency, and semantic knowledge. Causes of the deficit remain unclear in spite of many studies to investigate whether AD patients suffer from the inability to have voluntary access to an almost intact semantic store or from its break down. Word-stem completion (WSC) tasks have been utilized in healthy subjects in order to study semantic memory and network by exploiting the possibility of the involuntary access to them. Available conflicting data refer to the presence of semantic prime in AD patients. To explore the semantic network in AD, patients were requested to complete with the first word that sprang to their mind a stem submitted immediately after presentation of the word prime, as a WSC task. Stems consisted of the three beginning letters of words that were semantically related to primes. We compared data obtained with this task from patients with mild to moderate AD with those from normal controls (NC). AD patients completed less stems (P<0.001) with the expected words than NC, suggesting a break down of the semantic network rather than a deficit in the access to the semantic store.

  7. Frontal Lobe Function and Risk of Hip Fracture in Patient With Alzheimer Disease

    PubMed Central

    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

    2015-01-01

    Abstract 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. PMID:26559259

  8. G1/S Cell Cycle Checkpoint Defect in Lymphocytes from Patients with Alzheimer's Disease

    PubMed Central

    Song, Misun; Kwon, Young-Ah; Lee, Yujin; Kim, Hyeran; Yun, Ji Hea; Kim, Seonwoo

    2012-01-01

    Objective We compared the cell responsiveness of activated lymphocytes to rapamycin, which blocks the G1/S transition, between patients with Alzheimer's disease (AD) and normal controls to assess the early phase control defect in cell cycle. Methods Blood samples of 26 patients with AD and 28 normal controls were collected to separate peripheral lymphocytes. We measured the proportion of each cell cycle phase in activated lymphocytes using flow cytometry and evaluated the responsiveness of these lymphocytes to rapamycin. Results The patients with AD were older than the normal controls (AD 74.03±7.90 yr vs. control 68.28±6.21 yr, p=0.004). The proportion of G1 phase cells in the AD group was significantly lower than that in the control group (70.29±6.32% vs. 76.03±9.05%, p=0.01), and the proportion of S phase cells in the AD group was higher than that in control group (12.45±6.09% vs. 6.03±5.11%, p=0.001). Activated lymphocytes in patients with AD were not arrested in the G1 phase and they progressed to the late phase of the cell cycle despite rapamycin treatment, in contrast to those of normal subjects. Conclusion The patients with AD probably have a control defect of early phase cell cycle in peripheral lymphocytes that may be associated with the underlying pathology of neuronal death. PMID:23251208

  9. The economic costs of Alzheimer's disease.

    PubMed

    Hay, J W; Ernst, R L

    1987-09-01

    This paper estimates the economic costs of Alzheimer's Disease to individuals and to society, based on review of published Alzheimer's Disease-related research. The analysis is derived from epidemiological projections and cost information for the United States population in 1983. Estimated costs include both direct medical care and social support costs, as well as indirect costs, such as support services provided by family or volunteers, and the value of lost economic productivity in Alzheimer's Disease patients. Mid-range estimates of net annual expected costs for an Alzheimer's Disease patient, excluding the value of lost productivity, are $18,517 in the first year and $17,643 in subsequent years, with direct medical and social services comprising about half of these costs. Under base case assumptions, the total cost of disease per patient in 1983, was $48,544 to $493,277, depending upon patient's age at disease onset. The estimated present value of total net costs to society for all persons first diagnosed with Alzheimer's Disease in 1983 was $27.9-31.2 billion. Development of a public or private insurance market for the economic burdens of Alzheimer's Disease would fill some of the gaps in the current US system of financing long-term chronic disease care.

  10. Increased CD44 gene expression in lymphocytes derived from Alzheimer disease patients.

    PubMed

    Uberti, D; Cenini, G; Bonini, S A; Barcikowska, M; Styczynska, M; Szybinska, A; Memo, M

    2010-01-01

    In this study, we demonstrated for the first time an increased CD44 gene expression in lymphocytes derived from Alzheimer's disease (AD) patients in comparison with healthy subjects. CD44 is a surface antigen expressed by cells of the immune and central nervous system as well as in a variety of other tissues. Functioning as adhesion molecule, CD44 is furthermore involved in driving immune response into infected tissues, including the CNS. We also found that lymphocytes of the same patients expressed significant levels of unfolded p53 isoform, confirming what we already demonstrated in fibroblasts and lymphocytes derived from other cohorts of AD patients. A correlation between p53 and CD44 expression has been well demonstrated in cancer cells, suggesting that CD44 could be a target gene of mutant p53, or either mutant p53 could lack its ability to negatively regulate CD44 expression. The contemporaneous increased expression of unfolded p53 and CD44 in AD lymphocytes may suggest that these two molecules cross-talk together participating in peripheral immune response during the development of the disease.

  11. Demonstration of aluminum in amyloid fibers in the cores of senile plaques in the brains of patients with Alzheimer's disease.

    PubMed

    Yumoto, Sakae; Kakimi, Shigeo; Ohsaki, Akihiro; Ishikawa, Akira

    2009-11-01

    Aluminum (Al) exposure has been reported to be a risk factor for Alzheimer's disease (senile dementia of Alzheimer type), although the role of Al in the etiology of Alzheimer's disease remains controversial. We examined the presence of Al in the Alzheimer's brain using energy-dispersive X-ray spectroscopy combined with transmission electron microscopy (TEM-EDX). TEM-EDX analysis allows simultaneous imaging of subcellular structures with high spatial resolution and analysis of small quantities of elements contained in the same subcellular structures. We identified senile plaques by observation using TEM and detected Al in amyloid fibers in the cores of senile plaques located in the hippocampus and the temporal lobe by EDX. Phosphorus and calcium were also present in the amyloid fibers. No Al could be detected in the extracellular space in senile plaques or in the cytoplasm of nerve cells. In this study, we demonstrated colocalization of Al and beta-amyloid (Abeta) peptides in amyloid fibers in the cores of senile plaques. The results support the following possibilities in the brains of patients with Alzheimer's disease: Al could be involved in the aggregation of Abeta peptides to form toxic fibrils; Al might induce Abeta peptides into the beta-sheet structure; and Al might facilitate iron-mediated oxidative reactions, which cause severe damage to brain tissues.

  12. A blood based 12-miRNA signature of Alzheimer disease patients

    PubMed Central

    2013-01-01

    Background Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. We present a novel miRNA-based signature for detecting AD from blood samples. Results We apply next-generation sequencing to miRNAs from blood samples of 48 AD patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression levels. Of these, 82 have higher and 58 have lower abundance in AD patient samples. We selected a panel of 12 miRNAs for an RT-qPCR analysis on a larger cohort of 202 samples, comprising not only AD patients and healthy controls but also patients with other CNS illnesses. These included mild cognitive impairment, which is assumed to represent a transitional period before the development of AD, as well as multiple sclerosis, Parkinson disease, major depression, bipolar disorder and schizophrenia. miRNA target enrichment analysis of the selected 12 miRNAs indicates an involvement of miRNAs in nervous system development, neuron projection, neuron projection development and neuron projection morphogenesis. Using this 12-miRNA signature, we differentiate between AD and controls with an accuracy of 93%, a specificity of 95% and a sensitivity of 92%. The differentiation of AD from other neurological diseases is possible with accuracies between 74% and 78%. The differentiation of the other CNS disorders from controls yields even higher accuracies. Conclusions The data indicate that deregulated miRNAs in blood might be used as biomarkers in the diagnosis of AD or other neurological diseases. PMID:23895045

  13. Pharmacogenomics in Alzheimer's disease.

    PubMed

    Cacabelos, Ramón

    2002-02-01

    Alzheimer's disease (AD) is a complex disorder associated with multiple genetic defects either mutational or of susceptibility. Information available on AD genetics does not explain in full the etiopathogenesis of AD, suggesting that environmental factors and/or epigenetic phenomena may also contribute to AD pathology and phenotypic expression of dementia. The genomics of AD is still in its infancy, but is helping to understand novel aspects of the disease including genetic epidemiology, multifactorial risk factors, pathogenic mechanisms associated with genetic networks and genetically-regulated metabolic cascades. AD genomics is also helping to develop new strategies in pharmacogenomic research and prevention. Functional genomics, proteomics, pharmacogenomics, high-throughput methods, combinatorial chemistry and modern bioinformatics will greatly contribute to accelerate drug development for AD and other complex disorders. Main genes involved in AD include mutational loci (APP, PS1, PS2, TAU) and multiple susceptibility loci (APOE, A2M, AACT, LRP1, IL1A, TNF, ACE, BACE, BCHE, CST3, MTHFR, GSK3B, NOS) distributed across the human genome. Genomic associations integrate bigenic, trigenic, tetragenic or polygenic matrix models to investigate the genomic organization of AD in comparison to the control population. Similar genetic models are used in pharmacogenomics to elucidate genotype-specific responses of AD patients to a particular drug or combination of drugs. Using APOE-related monogenic models it has been demonstrated that the therapeutic response to drugs in AD is genotype-specific. A multifactorial therapy combining 3 different drugs yielded positive results during the 6-12 months in approximately 60% of the patients. With this therapeutic strategy, APOE-4/4 carriers were the worst responders, and patients with the APOE-3/4 genotype were the best responders. In bigenic and trigenic models it was possible to differentiate the influencial effect of PS1 and PS2

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

    PubMed Central

    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. PMID:26881032

  15. 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

  16. Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease

    PubMed Central

    Hayashi, Atsuko; Nomura, Hiroshi; Mochizuki, Ruriko; Ohnuma, Ayumu; Kimpara, Teiko; Suzuki, Kyoko; Mori, Etsuro

    2015-01-01

    Background/Aims We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji). Methods A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. Results For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. Conclusions The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients. PMID:26483830

  17. Validation of the route map recall test for getting lost behavior in Alzheimer's disease patients.

    PubMed

    Wang, Tsui-Ying; Kuo, Yen-Chun; Ma, Hui-Ing; Lee, Chih-Chien; Pai, Ming-Chyi

    2012-11-01

    Getting lost (GL) behavior is among the early symptoms in Alzheimer's disease (AD). Only a few tests, however, have been developed to screen for this symptom. The aim of this study was to develop an instrument, the Route Map Recall Test (RMRT), for the screening of the GL problem in AD patients. We examined the psychometric properties of the RMRT and its clinical utility to predict the GL risk in 23 AD patients and 43 cognitively healthy older adults. The results showed that the RMRT has a sound reliability (test-retest, r = .752, p < .001; Cronbach's α = 0.887, p < .001). The convergent validity was supported by the high correlations with Trail Making Test A and B. With the optimal criteria (93.5/104), the discriminative validity for the diagnosis of AD showed good sensitivity (86%) and specificity (70%), and sensitivity (100%) and specificity (67%) for GL in AD patients. The findings support the RMRT to be a useful tool for clinical screening of AD patients and their GL risk.

  18. How does an Alzheimer's disease patient's role in medical decision making change over time?

    PubMed

    Hirschman, Karen B; Xie, Sharon X; Feudtner, Chris; Karlawish, Jason H T

    2004-06-01

    As persons with Alzheimer's disease (AD) lose their ability to make decisions, someone else has to make decisions for them. We performed a prospective cohort study of 77 AD patient-caregiver dyads to examine when this transition occurs. When dementia severity surpassed a threshold marked by a Mini-Mental State Examination (MMSE) score less than 20, the level of caregiver-reported patient involvement in the medical decision-making process declined (Moderate [MMSE = 19-12]: Odds Ratio [OR] = 2.35, 95% confidence interval [95% CI] = 1.01-5.49; P =.048; Severe [MMSE < 12]: OR = 29.38, 95% CI = 5.98-144.25, P <.001). Furthermore, older patients (OR = 1.06, 95% CI = 1.00-1.12, P =.049) and mounting caregiver burden (OR = 1.12, 95% CI = 1.04-1.26, P =.003) were significant independent predictors of transitions to the caregiver-dominated medical decision-making process. These results provide clinicians with prognostic information that can help caregivers understand how their role in decision making will change over the course of a patient's dementing illness.

  19. Cognitive and neuropsychiatric correlates of EEG dynamic complexity in patients with Alzheimer's disease.

    PubMed

    Yang, Albert C; Wang, Shuu-Jiun; Lai, Kuan-Lin; Tsai, Chia-Fen; Yang, Cheng-Hung; Hwang, Jen-Ping; Lo, Men-Tzung; Huang, Norden E; Peng, Chung-Kang; Fuh, Jong-Ling

    2013-12-01

    This study assessed the utility of multiscale entropy (MSE), a complexity analysis of biological signals, to identify changes in dynamics of surface electroencephalogram (EEG) in patients with Alzheimer's disease (AD) that was correlated to cognitive and behavioral dysfunction. A total of 108 AD patients were recruited and their digital EEG recordings were analyzed using MSE methods. We investigate the appropriate parameters and time scale factors for MSE calculation from EEG signals. We then assessed the within-subject consistency of MSE measures in different EEG epochs and correlations of MSE measures to cognitive and neuropsychiatric symptoms of AD patients. Increased severity of AD was associated with decreased MSE complexity as measured by short-time scales, and with increased MSE complexity as measured by long-time scales. MSE complexity in EEGs of the temporal and occipitoparietal electrodes correlated significantly with cognitive function. MSE complexity of EEGs in various brain areas was also correlated to subdomains of neuropsychiatric symptoms. MSE analysis revealed abnormal EEG complexity across short- and long-time scales that were correlated to cognitive and neuropsychiatric assessments. The MSE-based EEG complexity analysis may provide a simple and cost-effective method to quantify the severity of cognitive and neuropsychiatric symptoms in AD patients. PMID:23954738

  20. 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.

  1. 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. PMID:26228165

  2. Leveraging existing data sets to generate new insights into Alzheimer's disease biology in specific patient subsets.

    PubMed

    Fowler, Kevin D; Funt, Jason M; Artyomov, Maxim N; Zeskind, Benjamin; Kolitz, Sarah E; Towfic, Fadi

    2015-09-23

    To generate new insights into the biology of Alzheimer's Disease (AD), we developed methods to combine and reuse a wide variety of existing data sets in new ways. We first identified genes consistently associated with AD in each of four separate expression studies, and confirmed this result using a fifth study. We next developed algorithms to search hundreds of thousands of Gene Expression Omnibus (GEO) data sets, identifying a link between an AD-associated gene (NEUROD6) and gender. We therefore stratified patients by gender along with APOE4 status, and analyzed multiple SNP data sets to identify variants associated with AD. SNPs in either the region of NEUROD6 or SNAP25 were significantly associated with AD, in APOE4+ females and APOE4+ males, respectively. We developed algorithms to search Connectivity Map (CMAP) data for medicines that modulate AD-associated genes, identifying hypotheses that warrant further investigation for treating specific AD patient subsets. In contrast to other methods, this approach focused on integrating multiple gene expression datasets across platforms in order to achieve a robust intersection of disease-affected genes, and then leveraging these results in combination with genetic studies in order to prioritize potential genes for targeted therapy.

  3. Leveraging existing data sets to generate new insights into Alzheimer's disease biology in specific patient subsets.

    PubMed

    Fowler, Kevin D; Funt, Jason M; Artyomov, Maxim N; Zeskind, Benjamin; Kolitz, Sarah E; Towfic, Fadi

    2015-01-01

    To generate new insights into the biology of Alzheimer's Disease (AD), we developed methods to combine and reuse a wide variety of existing data sets in new ways. We first identified genes consistently associated with AD in each of four separate expression studies, and confirmed this result using a fifth study. We next developed algorithms to search hundreds of thousands of Gene Expression Omnibus (GEO) data sets, identifying a link between an AD-associated gene (NEUROD6) and gender. We therefore stratified patients by gender along with APOE4 status, and analyzed multiple SNP data sets to identify variants associated with AD. SNPs in either the region of NEUROD6 or SNAP25 were significantly associated with AD, in APOE4+ females and APOE4+ males, respectively. We developed algorithms to search Connectivity Map (CMAP) data for medicines that modulate AD-associated genes, identifying hypotheses that warrant further investigation for treating specific AD patient subsets. In contrast to other methods, this approach focused on integrating multiple gene expression datasets across platforms in order to achieve a robust intersection of disease-affected genes, and then leveraging these results in combination with genetic studies in order to prioritize potential genes for targeted therapy. PMID:26395074

  4. Alzheimer and his disease: a brief history.

    PubMed

    Cipriani, Gabriele; Dolciotti, Cristina; Picchi, Lucia; Bonuccelli, Ubaldo

    2011-04-01

    More than 100 years ago, Alois Alzheimer first described the clinical and pathological features of an unusual brain disease during the meeting of the Society of Southwest German Psychiatrists in Tübingen: the patient, Auguste Deter, suffered memory loss, disorientation, hallucinations and delusions and died at the age of 55. In 1910, Emil Kraepelin named the condition with the eponym of "Alzheimer's disease" (AD) that is, now, the most common neurodegenerative disease with more than 25 million cases worldwide and a major medical problem nearing catastrophic levels. The present article discusses Alzheimer's work in the context of his life and time.

  5. 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.

  6. Regional analysis of spontaneous MEG rhythms in patients with Alzheimer's disease using spectral entropies.

    PubMed

    Poza, Jesús; Hornero, Roberto; Escudero, Javier; Fernández, Alberto; Sánchez, Clara I

    2008-01-01

    Alzheimer's disease (AD) is the most common form of dementia. Ageing is the greatest known risk factor for this disorder. Therefore, the prevalence of AD is expected to increase in western countries due to the rise in life expectancy. Nowadays, a low diagnosis accuracy is reached, but an early and accurate identification of AD should be attempted. In this sense, only a few studies have focused on the magnetoencephalographic (MEG) AD patterns. This work represents a new effort to explore the ability of three entropies from information theory to discriminate between spontaneous MEG rhythms from 20 AD patients and 21 controls. The Shannon (SSE), Tsallis (TSE), and Rényi (RSE) spectral entropies were calculated from the time-frequency distribution of the power spectral density (PSD). The entropies provided statistically significant lower values for AD patients than for controls in all brain regions (p < 0.0005). This fact suggests a significant loss of irregularity in AD patients' MEG activity. Maximal accuracy of 87.8% was achieved by both the TSE and RSE (90.0%, sensitivity; 85.7%, specificity). The statistically significant results obtained by both the extensive (SSE and RSE) and non-extensive (TSE) spectral entropies suggest that AD could disturb long and short-range interactions causing an abnormal brain function.

  7. 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

  8. 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

  9. Studies of implicit prototype extraction in patients with mild cognitive impairment and early Alzheimer's disease.

    PubMed

    Nosofsky, Robert M; Denton, Stephen E; Zaki, Safa R; Murphy-Knudsen, Anne F; Unverzagt, Frederick W

    2012-07-01

    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; Knowlton & Squire, 1993). However, alternative interpretations are that (a) even people with impairments to a single memory system have sufficient resources to succeed on the particular categorization tasks that have been tested (Nosofsky & Zaki, 1998; Zaki & Nosofsky, 2001) and (b) working memory can be used at time of test to learn the categories (Palmeri & Flanery, 1999). In the present experiments, patients with amnestic mild cognitive impairment or early Alzheimer's disease were tested in prototype-extraction tasks to examine these possibilities. In a categorization task involving discrete-feature stimuli, the majority of subjects relied on memories for exceedingly few features, even when the task structure strongly encouraged reliance on broad-based prototypes. In a dot-pattern categorization task, even the memory-impaired patients were able to use working memory at time of test to extract the category structure (at least for the stimulus set used in past work). We argue that the results weaken the past case made in favor of a separate system of implicit prototype extraction.

  10. [Diabetes mellitus and Alzheimer's disease].

    PubMed

    Salacz, Pál; Csibri, Eva

    2011-03-27

    The incidence of Alzheimer's disease and diabetes is increasing with age. Thus, in light of demographic change and aging societies, they are becoming a growing issue for public health. Further, there are linkages between the two diseases. In particular, risk assessment studies suggest that type 2 diabetes mellitus is a risk factor of Alzheimer's disease. Hence, even though Alzheimer's disease can only be influenced to a limited extent, optimal treatment of diabetes mellitus may have also a positive effect on Alzheimer's disease. While the relationship between the two diseases is not yet completely clear, in addition to the known vascular effects of diabetes mellitus recent results shed light on central nervous system effects directly influencing the neurodegenerative process. Treatment of central insulin resistance, a phenomenon explored in recent years, may be a promising avenue, not only in addressing metabolic disorder, but also Alzheimer's disease.

  11. [Clinical symptoms of Alzheimer disease].

    PubMed

    Tariska, P; Urbanics, K; Knolmayer, J; Mészáros, A

    1995-04-23

    Data of patients suffering from Alzheimer's disease and checked out in the special unit named Memory Clinic functioning from 1992 in the National Institute of Psychiatry and Neurology are summarized. Age average of the 60 patients was 63 years, the first symptoms of the disease had appeared in 57 p.c. before the age of 65, so the classical presenile form of the ailment is represented too in the material. Predominance of multifocal cortical function disturbances in the symptomatology is characteristic, association of the depression is outstandingly frequent. The atypical features, or those characteristic in diseases of cerebrovascular origin are not infrequently seen (headache, dizziness, slight symptoms of pyramidal lesions). The absence of epileptic seizures It was interesting even in considering the data of the literature too. The main points of clinical diagnostics and differential diagnostics are demonstrated with the aid of case reports. The author's material is the first Hungarian publication in the topics of clinical symptoms of patients suffering from Alzheimer's disease that had been investigated with up-to-date methods. Occurrence of the disease of very great frequency could be supposed to occur at general practitioners, the importance of differential diagnostics and planning of the complex longlasting therapy is extremely great.

  12. 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…

  13. 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

  14. 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.

  15. 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

  16. 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. PMID:18534566

  17. 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.

  18. 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

  19. L-dopa modulates motor cortex excitability in Alzheimer's disease patients.

    PubMed

    Martorana, Alessandro; Stefani, Alessandro; Palmieri, Maria Giuseppina; Esposito, Zaira; Bernardi, Giorgio; Sancesario, Giuseppe; Pierantozzi, Mariangela

    2008-09-01

    In Alzheimer's disease (AD), transcranial magnetic stimulation (TMS) studies have shown abnormalities of motor cortical excitability, such as a decreased intra-cortical inhibition (ICI) and changes in resting motor threshold (rMT). We studied the effects of L-dopa on rMT and ICI in a cohort of moderate AD patients after paired-pulse TMS. Results were compared with a control group of healthy subjects. As expected, AD patients showed a significant reduction in ICI and a lower rMT. L-dopa administration (soluble form, melevodopa 200 mg) promptly reversed the ICI impairment up to normalization. This effect was specific, since it was not mimicked in control subjects. These results indicate a possible role of dopamine in modulating AD cortical excitability, thus suggesting an interaction between dopaminergic ascending pathways and endogenous intracortical transmitters. In addition, considering that L-dopa showed a pharmacological profile similar to the one of cholinomimetics, L-dopa might represent a reliable tool to study new therapeutic perspective and strategies for AD.

  20. Assessing Alzheimer's disease patients with the Cohen-Mansfield Agitation Inventory: scoring and clinical implications.

    PubMed

    Weiner, Myron F; Tractenberg, Rochelle E; Jin, Shelia; Gamst, Anthony; Thomas, Ronald G; Koss, Elisabeth; Thal, Leon J

    2002-01-01

    We explored the applicability of the standard scoring of the Cohen-Mansfield Agitation Inventory (CMAI), a widely used nursing-home derived instrument, to community-dwelling persons with Alzheimer's disease (AD). Item responses to the CMAI were gathered from participants in two large clinical studies, one of which specifically included patients with behavioral disturbances. Confirmatory factor analysis in these two groups of well-characterized AD patients suggested that conventional CMAI subscoring did not adequately describe the responses of these two groups. Exploratory factor analysis indicated that the four CMAI subscores, based on a verbal-physical and aggressive-non-aggressive conceptualization of behavioral disturbance, did not fit community dwelling persons with AD. Based on cross-sectional and longitudinal analyses, there was suggestive evidence for three behavioral clusters, but these clusters did not achieve statistical significance Overall, the CMAI seemed best suited to describe the overall level rather than the specific subtypes of behavioral dyscontrol in community-dwelling persons with AD. PMID:11755457

  1. Alzheimer's Disease Beyond Abeta.

    PubMed

    Town, Terrence

    2010-05-01

    Many of the Alzheimer's disease (AD) clinical trials have made it far enough down the pipeline to allow conclusions about targeting the amyloid-beta peptide (Abeta) as a therapeutic approach. Based on these results, it is becoming clear that a multifocal approach to AD treatment is probably necessary. However, critical discussion beyond Abeta is necessary to enable the next wave of AD therapeutic targets. For this reason, the 2010 Keystone Symposium, 'Alzheimer's Disease Beyond Abeta', was organized by JoAnne McLaurin and Tony Wyss-Coray to spark topical discussion and debate. While researchers struggled to get beyond that ever-present pathognomonic feature of AD, new and exciting evidence was presented that raised our awareness of what is around the corner for next-generation AD therapeutics beyond Abeta. This report will describe some of the highlights from Copper Mountain Resort throughout the meeting period of 10-15 January 2010 in Colorado (USA). Despite illuminating scientific presentations and intense discussions, a number of important questions remain concerning the best biomarkers and targets to focus on, and when and how to therapeutically intervene. PMID:20429127

  2. Osteopontin is increased in the cerebrospinal fluid of patients with Alzheimer's disease and its levels correlate with cognitive decline.

    PubMed

    Comi, Cristoforo; Carecchio, Miryam; Chiocchetti, Annalisa; Nicola, Stefania; Galimberti, Daniela; Fenoglio, Chiara; Cappellano, Giuseppe; Monaco, Francesco; Scarpini, Elio; Dianzani, Umberto

    2010-01-01

    Inflammation is believed to play a role in Alzheimer's disease (AD). Osteopontin (OPN) is a molecule involved in macrophage recruitment and activation and implicated in neurodegeneration. In order to elucidate the role of OPN in AD, we evaluated its levels in serum and cerebrospinal fluid (CSF) of 67 AD patients, 46 frontotemporal dementia (FTD) patients, and 69 controls. We found that OPN levels: i) are significantly increased in the CSF of AD patients; ii) correlate with MMSE score; and iii) are higher in the early disease phases ( 2 years). These findings support a role of OPN in AD pathogenesis. PMID:20308780

  3. 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

  4. Exploring Visual Selective Attention towards Novel Stimuli in Alzheimer's Disease Patients

    PubMed Central

    Chau, Sarah A.; Herrmann, Nathan; Eizenman, Moshe; Chung, Jonathan; Lanctôt, Krista L.

    2015-01-01

    Background Alzheimer's disease (AD) is associated with selective attention impairments, which could contribute to cognitive and functional deficits. Selective attention can be explored through examination of novelty preference. Aims In this study, we quantified novelty preference in AD patients by measuring visual scanning behaviour using an eye tracking paradigm. Methods Mild-to-moderate AD patients and elderly controls viewed slides containing novel and repeated images simultaneously. The outcome measure was time spent on specific images, with novelty preference defined by greater relative fixation time (RFT) on novel versus repeated images. Cognitive status (Standardized Mini-Mental State Examination, SMMSE) and attention (Digit Span, DS) were also measured. Results AD patients (age 79.2 ± 6.7 years, SMMSE 22.2 ± 4.0, n = 41) and controls (age 76.2 ± 6.4 years, SMMSE 28.1 ± 2.0, n = 24) were similar in age, education and sex. Compared with controls, AD patients had lower RFT on novel than on repeated images (F1,63 = 11.18, p = 0.001). Further, reduced RFT was associated with lower scores on SMMSE (r63 = 0.288, p = 0.020) and DS (r63 = 0.269, p = 0.030). Within individuals, novelty preference was detected in 92.3% of patients and in 100% of controls. Conclusion These findings suggest that novelty preference, measured by visual scanning behaviour, can differentiate cognitively healthy and impaired people and may offer a nonverbal, less cognitively demanding method of assessing selective attention. PMID:26955382

  5. Investigating Associative Learning Effects in Patients with Prodromal Alzheimer's Disease Using the Temporal Context Model.

    PubMed

    Quenon, Lisa; de Xivry, Jean-Jacques Orban; Hanseeuw, Bernard; Ivanoiu, Adrian

    2015-10-01

    The purpose of this study was to investigate associative learning effects in patients with prodromal Alzheimer's disease (prAD) by referring to the Temporal Context Model (TCM; Howard, Jing, Rao, Provyn, & Datey, 2009), in an attempt to enhance the understanding of their associative memory impairment. TCM explains fundamental effects described in classical free-recall tasks and cued-recall tasks involving overlapping word pairs (e.g., A-B, B-C), namely (1) the contiguity effect, which is the tendency to successively recall nearby items in a list, and (2) the observation of backward (i.e., B-A) and transitive associations (i.e., A-C) between items. In TCM, these effects are hypothesized to rely on contextual representation, binding and retrieval processes, which supposedly depend on hippocampal and parahippocampal regions. As these regions are affected in prAD, the current study investigated whether prAD patients would show reduced proportions of backward and transitive associations in free and cued-recall, coupled to a reduced contiguity effect in free-recall. Seventeen older controls and 17 prAD patients performed a cued-recall task involving overlapping word pairs and a final free-recall task. Proportions of backward and transitive intrusions in cued-recall did not significantly differ between groups. However, in free-recall, prAD patients demonstrated a reduced contiguity effect as well as reduced proportions of backward and transitive associations compared to older controls. These findings are discussed within the hypothesis that the contextual representation, binding and/or retrieval processes are affected in prAD patients compared to healthy older individuals. PMID:26411265

  6. 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.

  7. Therapeutic perspectives in Alzheimer's disease.

    PubMed

    Tschäpe, Jakob-A; Hartmann, Tobias

    2006-01-01

    It is now almost a century ago that Alois Alzheimer first presented his results in public. Main characteristics of Alzheimer's disease (AD) are massive cerebral accumulation of amyloid, composed of fibrillary aggregates of the Amyloid beta peptide (Abeta) and intracellular accumulation of abnormally phosphorylated tau protein associated with widespread neurodegeneration. The clinical picture is characterized by progressive and irreversible dementia, which is eventually fatal. To date, there is no cure for this severe disease affecting more than of 30 million individuals worldwide. In the last decades, the treatment of Alzheimer patients was mainly focusing on symptomatical strategies. Based on the augmented knowledge about the mechanisms underlying the pathology of AD, particularly the molecular causes and consequences of AD, different therapeutic approaches arose and recently, treatment with Statins, NSAIDs and Abeta vaccines reached the level of clinical trials, showing some indication of efficacy already. According to actual evaluations, these approaches have realistic chances to become established as therapeutic routine in AD within the next 10 years. We will review here some of the most promising novel approaches to cure and prevent rather than to treat the symptoms of AD.

  8. An exploratory case study of the impact of ambient biographical displays on identity in a patient with Alzheimer's disease.

    PubMed

    Massimi, Michael; Berry, Emma; Browne, Georgina; Smyth, Gavin; Watson, Peter; Baecker, Ronald M

    2008-01-01

    One of the most troubling symptoms of Alzheimer's disease is the loss of the patient's sense of identity. This loss complicates relationships, increases apathy, and generally impedes quality of life for the patient. We describe a novel in-home ambient display called Biography Theatre that cycles through music, photographs, movies, and narratives drawn from the patient's past and current life. We conducted an exploratory case study with an 84-year-old male with moderate-stage Alzheimer's disease (Mr H). The study consisted of three phases: a baseline phase, a phase wherein autobiographical materials were collected and discussed, and a phase wherein the display was deployed in the home. The patient demonstrated improvement on standardised tests of apathy and positive self-identity, but did not improve on tests of autobiographical memory, anxiety, depression, and general cognition. We also report on caregiver reactions to the intervention and how the display helped them cope with and reinterpret their loved one's condition. This work suggests that interdisciplinary work involving "off the desktop" computing technologies may be a fruitful way to provide rehabilitative benefit for individuals with Alzheimer's disease.

  9. The safety and tolerability of donepezil in patients with Alzheimer's disease

    PubMed Central

    Jackson, Stephen; Ham, Richard J; Wilkinson, David

    2004-01-01

    Cholinesterase (ChE) inhibitors, which prevent the hydrolysis of acetylcholine, have been approved for the symptomatic treatment of Alzheimer's disease (AD) for over a decade. However, the first ChE inhibitors were associated with a high incidence of side-effects and general tolerability concerns, including hepatotoxicity. Side-effects associated with increased cholinergic activity, particularly in the gastrointestinal (GI) system, can prevent patients from achieving effective doses of drug. In addition, the advanced age and frail nature of patients with AD mean that poor tolerability is a serious concern. The potential for drug–drug interactions is also an important consideration, due to the high prevalence of comorbid disease in these patients. Data both from clinical trials and studies in routine clinical practice have shown that donepezil is associated with a low incidence of GI adverse events (AEs) that is comparable with placebo. Donepezil is a potent, selective inhibitor of acetylcholinesterase, and selective inhibition of central as opposed to peripheral ChEs might be expected to reduce the incidence of AEs, thus this may explain the lower incidence of cholinergic AEs observed following treatment with donepezil, compared with nonselective ChE inhibitors. There are no differences in cardiovascular AEs, including bradycardia, between placebo and donepezil groups in the clinical trials published to date, even in a very sick vascular dementia population with high rates of comorbidity and concomitant medication use. Data from single- and multiple-dose studies of donepezil in patients with hepatic impairment and with moderately to severely impaired renal function indicate that donepezil is safe and well tolerated in these groups. Furthermore, both in vitro and clinical studies have shown that donepezil is not associated with drug–drug interactions. The incidence of weight loss is very similar between donepezil- and placebo-treated patients. Although insomnia

  10. 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.

  11. Do cholinesterase inhibitors act primarily on attention deficit? A naturalistic study in Alzheimer's disease patients.

    PubMed

    Bracco, Laura; Bessi, Valentina; Padiglioni, Sonia; Marini, Sandro; Pepeu, Giancarlo

    2014-01-01

    Attention is the first non-memory domain affected in Alzheimer's disease (AD), before deficits in language and visuo-spatial function, and it is claimed that attention deficits are responsible for the difficulties with daily living in early demented patients. The aim of this longitudinal study in a group of 121 Caucasian, community-dwelling, mild-to-moderate AD patients (Mini-Mental State Examination (MMSE) score >17) was to detect which cognitive domains were most affected by the disease and whether one year treatment with cholinesterase inhibitors was more effective in preserving attention than memory. All subjects were evaluated by a neuropsychological battery including global measurements (MMSE, Information-Memory-Concentration Test) and tasks exploring verbal long-term memory, language, attention, and executive functions. The comparison between two evaluations, made 12 months apart, shows statistically significant differences, indicating deterioration compared to baseline, in the following tests: MMSE (with no gender differences), Composite Memory Score, Short Story Delayed Recall, Trail-Making Test A, Semantic Fluency Test, and Token Test. Conversely, there were no differences in the two evaluations of the Digit Span, Corsi Tapping Test, Short Story Immediate Recall, and Phonemic Fluency Tests. It appears that the treatment specifically attenuated the decline in tests assessing attention and executive functions. A stabilization of the ability to pay attention, with the ensuing positive effects on executive functions, recent memory, and information acquisition which depend on attention, appears to be the main neuropsychological mechanism through which the activation of the cholinergic system, resulting from cholinesterase inhibition, exerts its effect on cognition. PMID:24577458

  12. 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. PMID:26441643

  13. Context Memory in Alzheimer's Disease

    PubMed Central

    El Haj, Mohamad; Kessels, Roy P.C.

    2013-01-01

    Background Alzheimer's disease (AD) is a neurodegenerative disease characterized by a gradual loss of memory. Specifically, context aspects of memory are impaired in AD. Our review sheds light on the neurocognitive mechanisms of this memory component that forms the core of episodic memory function. Summary Context recall, an element of episodic memory, refers to remembering the context in which an event has occurred, such as from whom or to whom information has been transmitted. Key Messages Our review raises crucial questions. For example, (1) which context element is more prone to being forgotten in the disease? (2) How do AD patients fail to bind context features together? (3) May distinctiveness heuristic or decisions based on metacognitive expectations improve context retrieval in these patients? (4) How does cueing at retrieval enhance reinstating of encoding context in AD? By addressing these questions, our work contributes to the understanding of the memory deficits in AD. PMID:24403906

  14. 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

  15. 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

  16. [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. PMID:22277519

  17. [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.

  18. 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.

  19. 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. PMID:26455564

  20. 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.

  1. NK Cells are Activated in Amnestic Mild Cognitive Impairment but not in Mild Alzheimer's Disease Patients.

    PubMed

    Le Page, Aurélie; Bourgade, Karine; Lamoureux, Julie; Frost, Eric; Pawelec, Graham; Larbi, Anis; Witkowski, Jacek M; Dupuis, Gilles; Fülöp, Tamás

    2015-01-01

    Alzheimerś disease (AD) is a progressive irreversible neurological brain disorder characterized by accumulation of amyloid-β, amyloid plaques, and neurofibrillary tangles. Inflammation and immune alterations have been linked to AD, suggesting that the peripheral immune system plays a role during the asymptomatic period of AD. NK cells participate in innate immune surveillance against intracellular pathogens and malignancy but their role in AD remains controversial. We have investigated changes in peripheral NK cell phenotypes and functions in amnestic mild cognitive impairment (aMCI, n = 10), patients with mild AD (mAD, n = 11), and healthy elderly controls (n = 10). Patients selected according to NINCDS-ADRDA criteria were classified using neuropsychological assessment tests. Phenotype analysis revealed differences in expression of CD16 (increased in mAD), NKG2A (decreased in aMCI), and TLR2 and TLR9 (both decreased in mAD). Functional assays revealed that NK cell killing activity and degranulation (CD107 expression) were unchanged in the three groups. In contrast, expression of the CD95 receptor was increased in aMCI and mAD. Granzyme B expression and cytokine production (TNFα, IFNγ) were increased in aMCI but not in mAD. CCL19- but not CCL21-dependent chemotaxis was decreased in aMCI and mAD, despite the fact that CCR7 expression was increased in aMCI. Our data suggest that the number of alterations observed in peripheral NK cells in aMCI represent an activation state compared to mAD patients and that may reflect an active immune response against a still to be defined aggression.

  2. 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

    2016-01-01

    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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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…

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Cognitive aging and Alzheimer's disease

    PubMed Central

    Vandenberghe, R; Tournoy, J

    2005-01-01

    Cognitive aging and clinically probable Alzheimer's disease can be discriminated by means of clinical and neuropsychological testing, and structural and functional imaging techniques. Research at the level of cognitive brain systems and at the molecular level provides exciting new insights into the relation between aging and neurodegeneration. The advances at the clinical and at the basic research levels are necessary if we wish to meet the formidable challenge that the increasing prevalence of Alzheimer's disease poses to the medical community. PMID:15937198

  14. 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 ... How many people in the United States have Alzheimer's disease? as many as 5.1 million as ...

  15. 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.

  16. Memory Test Performance on Analogous Verbal and Nonverbal Memory Tests in Patients with Frontotemporal Dementia and Alzheimer's Disease

    PubMed Central

    Baldock, Deanna; Miller, Justin B.; Leger, Gabriel C.; Banks, Sarah Jane

    2016-01-01

    Background Patients with frontotemporal dementia (FTD) typically have initial deficits in language or changes in personality, while the defining characteristic of Alzheimer's disease (AD) is memory impairment. Neuropsychological findings in the two diseases tend to differ, but can be confounded by verbal impairment in FTD impacting performance on memory tests in these patients. Methods Twenty-seven patients with FTD and 102 patients with AD underwent a neuropsychological assessment before diagnosis. By utilizing analogous versions of a verbal and nonverbal memory test, we demonstrated differences in these two modalities between AD and FTD. Discussion Better differentiation between AD and FTD is found in a nonverbal memory test, possibly because it eliminates the confounding variable of language deficits found in patients with FTD. These results highlight the importance of nonverbal learning tests with multiple learning trials in diagnostic testing. PMID:26933437

  17. Ideational Action Impairments in Alzheimer's Disease

    ERIC Educational Resources Information Center

    Chainay, H.; Louarn, C.; Humphreys, G. W.

    2006-01-01

    We report data from a group of patients with mild Alzheimer's disease on a range of tasks requiring either stored semantic knowledge about objects (e.g., naming object use) or the execution of action to objects (e.g., miming and using objects). We found that the patients were impaired at miming in response to objects, even when they could describe…

  18. 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…

  19. Expressed emotion and attributions in the carers of patients with Alzheimer's disease: the effect on carer burden.

    PubMed

    Tarrier, Nicholas; Barrowclough, Christine; Ward, Jonathan; Donaldson, Catherine; Burns, Alistair; Gregg, Lynsey

    2002-05-01

    Burden of care, expressed emotion (EE), causal attributions, and salivary cortisol were assessed in 100 carers of patients with Alzheimer's disease. Forty-one carers were rated high EE, which was associated with higher scores of carer distress and strain, and greater reports of noncognitive features in the patient, but not with cortisol levels. High EE carers made more attributions personal to, and controllable by, the patient for negative events. Critical carers made more attributions of the patient's behavior that was idiosyncratic. Warmth toward the patient was associated with the opposite of this pattern. Overinvolved carers made attributions of the patient's behavior to causes external to the patient and internal to themselves. Cortisol levels were associated with self-reports of strain and distress. PMID:12003455

  20. Autotoxicity and Alzheimer disease.

    PubMed

    McGeer, P L; McGeer, E G

    2000-06-01

    I mmunological responses are considered to be either humoral, resulting from cloning of B lymphocytes, or cell mediated, resulting from cloning of T lymphocytes. Autoimmune diseases occur when the cloned products attack host tissue. Inflammation is considered a nonspecific response to injury, characterized by exudation of serum into damaged tissue, and identified by the cardinal signs of rubor, calor, dolor, and tumor. However, these classic mechanisms do not fit pathological observations of Alzheimer disease (AD)-affected brain tissue. Although many of the components prominently associated with peripheral immunological and inflammatory states are present in AD lesions, there are no identifiable B lymphocytes or antibodies, and T cells are sparse. Furthermore, the blood-brain barrier is intact, excluding exudation of exogenous serum proteins. Although "neuroinflammation" is the term commonly used to describe the pathological changes, it fails to define adequately the process that is taking place. The reaction is neither a nonspecific response to injury, as classically implied for inflammatory reactions, nor an autoimmune reaction, despite the directed attack against plaques and extracellular tangles. It is most appropriately defined as an innate immunoreaction. The fact that such a reaction can be mounted by brain, an organ frequently described as being immunologically privileged, suggests that a reevaluation is required of the dimensions of the innate immune system, including how it operates at the tissue level. The innate immune system is primitive, while the adaptive immune system, which is directed by peripheral immune organs, is an invention of vertebrates. Even in vertebrates, however, the innate immune system is the first line of defense. Much more needs to be learned about the operation of the innate immune system in health and disease. Arch Neurol. 2000.

  1. Importance and management of micronutrient deficiencies in patients with Alzheimer's disease.

    PubMed

    Cardoso, Bárbara Rita; Cominetti, Cristiane; Cozzolino, Silvia Maria Franciscato

    2013-01-01

    Alzheimer's disease (AD) is the most common form of dementia, and it generally affects the elderly. It has been suggested that diet is an intensively modifiable lifestyle factor that might reduce the risk of AD. Because epidemiological studies generally report the potential neuronal protective effects of various micronutrients, the aim of this study was to perform a literature review on the major nutrients that are related to AD, including selenium, vitamins C and E, transition metals, vitamin D, B-complex vitamins, and omega-3 fatty acids. PMID:23696698

  2. Exploring Biomarkers for Alzheimer's Disease.

    PubMed

    Sharma, Neeti; Singh, Anshika Nikita

    2016-07-01

    Alzheimer's Disease (AD) is one of the most common form of dementia occurring in elderly population worldwide. Currently Aβ42, tau and p-tau in the cerebrospinal fluid is estimated for confirmation of AD. CSF which is being used as the potent source for biomarker screening is obtained by invasive lumbar punctures. Thus, there is an urgent need of minimal invasive methods for identification of diagnostic markers for early detection of AD. Blood serum and plasma serves as an appropriate source, due to minimal discomfort to the patients, promoting frequent testing, better follow-up and better consent to clinical trials. Hence, the need of the hour demands discovery of diagnostic and prognostic patient specific signature biomarkers by using emerging technologies of mass spectrometry, microarrays and peptidomics. In this review we summarize the present scenario of AD biomarkers such as circulatory biomarkers, blood based amyloid markers, inflammatory markers and oxidative stress markers being investigated and also some of the potent biomarkers which might be able to predict early onset of Alzheimer's and delay cognitive impairment. PMID:27630867

  3. Leptin in Alzheimer's disease.

    PubMed

    Magalhães, C A; Carvalho, M G; Sousa, L P; Caramelli, P; Gomes, K B

    2015-10-23

    Alzheimer's disease (AD) is the most common cause of progressive dementia in the elderly population. AD is histologically characterized by accumulation of amyloid-β protein (Aβ) on extracellular plaques and deposition of hyperphosphorylated tau protein in intracellular neurofibrillary tangles. Several studies have shown that obesity may precede dementia and that lifestyle factors play a critical role in the onset of AD. Furthermore, accumulating evidence indicates that obesity is an independent risk factor for developing AD. In this scenario, the understanding of the role of adipose tissue in brain health is essential to clarify the establishment of demential processes. The objective of this work was to review studies regarding leptin, an anorexigenic peptide hormone synthesized in adipocytes, in the context of dementia. Some authors proposed that leptin evaluation might be a better predictor of dementia than traditional anthropometric measures. Leptin, once established as a biomarker, could enhance the understanding of late-onset AD risk over the life course, as well as the clinical progression of prodromal state to manifested AD. Other studies have proposed that leptin presents neuroprotective activities, which could be explained by inhibiting the amyloidogenic process, reducing the levels of tau protein phosphorylation and improving the cognitive function.

  4. The immune system, amyloid-beta peptide, and Alzheimer's disease.

    PubMed

    Weksler, Marc E; Gouras, Gunnar; Relkin, Norman R; Szabo, Paul

    2005-06-01

    In this review, the case is made that amyloid-beta peptide in the brain of patients with Alzheimer's disease is a primary cause of the disease and that immunotherapy directed against this peptide has the potential to halt and/or reverse disease progression. This supposition is supported by the capacity of anti-beta-amyloid peptide antibodies to prevent or reverse the disease in mouse models of Alzheimer's disease. Furthermore, preliminary results obtained in a small number of patients with Alzheimer's disease are consistent with the observations made in the mouse model of this disease. We review the relationship between the immune system, amyloid-beta peptide, and Alzheimer's disease and the progress made in applying immunotherapy to patients with Alzheimer's disease.

  5. Successful non-operative management of spontaneous type II gallbladder perforation in a patient with Alzheimer's disease.

    PubMed

    Alessiani, Mario; Peloso, Andrea; Tramelli, Paola; Magnani, Enzo

    2014-01-01

    A 77-year-old man with Alzheimer's disease was admitted to a rural hospital in June 2012 and an acute cholecistytis was first diagnosed. Surgery was not considered as a possible option due to the critical condition of the patient and his severe comorbidities. After 2 days of broad-spectrum antibiotics, the patient worsened and developed severe sepsis. A gallbladder perforation with intrahepatic abscess formation was diagnosed on ultrasonography (US) and abdominal CT scan. The patient underwent percutaneous US-guided gallbladder drainage with resolution of the sepsis and rapid clinical improvement. After 1 month, the drainage was removed and the patient was discharged. He survived in good condition for 18 months and he passed away from pneumonitis in December 2013. This case shows that in a case of acute cholecystitis with gallbladder perforation, percutaneous gallbladder drainage can be a lifesaving procedure in elderly patients with severe comorbidities (including Alzheimer's disease) who are not candidates for elective surgery.

  6. 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.

  7. 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.

  8. The Effectiveness and Safety of Acupuncture for Patients With Alzheimer Disease

    PubMed Central

    Zhou, Jing; Peng, Weina; Xu, Min; Li, Wang; Liu, Zhishun

    2015-01-01

    Abstract The use of acupuncture for treating Alzheimer disease (AD) has been increasing in frequency over recent years. As more studies are conducted on the use of acupuncture for treating AD, it is necessary to re-assess the effectiveness and safety of this practice. The objective of this study was to assess the effectiveness and safety of acupuncture for treating AD. Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE, Embase, PsycINFO, Chinese Biomedicine Literature (CBM), Chinese Medical Current Content (CMCC) and China National Knowledge Infrastructure (CNKI) were searched from their inception to June 2014. Randomized controlled trials (RCTs) with AD treated by acupuncture or by acupuncture combined with 1 kind of drugs were included. Two authors extracted data independently. The continuous data were expressed as mean differences (MD) with 95% confidence intervals (CIs). Weighted MD (WMD) was used instead of standardized MD (SMD) when the same scales were used. Adverse reactions related to acupuncture were also investigated. Ten randomized controlled trials with a total of 585 participants were included in the meta-analysis. The combined results of 6 trials showed that acupuncture was better than drugs at improving scores on the Mini Mental State Examination (MMSE) scale (MD 1.05, 95% CI 0.16–1.93). Evidence from the pooled results of 3 trials showed that acupuncture plus donepezil was more effective than donepezil alone at improving the MMSE scale score (MD 2.37, 95% CI 1.53–3.21). Out of 141 clinical trials, 2 trials reported the incidence of adverse reactions related to acupuncture. Seven out of 3416 patients had adverse reactions related to acupuncture during or after treatment; the reactions were described as tolerable and not severe. Acupuncture may be more effective than drugs and may enhance the effect of drugs for treating AD in terms of improving cognitive function. Acupuncture may also be more effective than drugs at improving AD

  9. Noradrenergic dysfunction in Alzheimer's disease

    PubMed Central

    Gannon, Mary; Che, Pulin; Chen, Yunjia; Jiao, Kai; Roberson, Erik D.; Wang, Qin

    2015-01-01

    The brain noradrenergic system supplies the neurotransmitter norepinephrine throughout the brain via widespread efferent projections, and plays a pivotal role in modulating cognitive activities in the cortex. Profound noradrenergic degeneration in Alzheimer's disease (AD) patients has been observed for decades, with recent research suggesting that the locus coeruleus (where noradrenergic neurons are mainly located) is a predominant site where AD-related pathology begins. Mounting evidence indicates that the loss of noradrenergic innervation greatly exacerbates AD pathogenesis and progression, although the precise roles of noradrenergic components in AD pathogenesis remain unclear. The aim of this review is to summarize current findings on noradrenergic dysfunction in AD, as well as to point out deficiencies in our knowledge where more research is needed. PMID:26136654

  10. 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 ...

  11. The burden of Alzheimer's disease.

    PubMed

    Burns, Alistair

    2000-07-01

    Alzheimer's disease (AD) imposes a severe burden upon patients and their carers. In particular, family carers of AD patients face extreme hardship and distress that represents a major but often hidden burden on healthcare systems. Carers often experience clinically significant alterations in physical and mental health, particularly depression. A number of individual features of the dementia syndrome that are known to be particularly burdensome to carers include the degree of cognitive impairment, amount of help required with activities of daily living, personality changes and the presence of psychiatric symptoms and behavioural disturbances. The neuropsychiatric features of AD patients can adversely impact the relationship between the patient and caregiver generating feelings of strain, burden and social isolation. Individual characteristics of the caregiver including personality, gender, degree of formal and informal support and physical and mental health, as well as attributional style ('coping style') and expressed emotion (critical or hostile attitudes), also dictate carer burden. As informal caregivers play such a crucial role in the care of AD patients, appropriate management strategies that incorporate interventions which address the specific burdens of the individual caregiver are essential. Reducing the burden of care can be achieved by the combination of a number of individual and general measures, including education, respite and emotion-focused interventions. These measures, accompanied by non-pharmacological strategies, are extremely important in the total care of the AD patient, with the emphasis on maintaining people in the community as long as possible.

  12. An attenuation of the 'normal' category effect in patients with Alzheimer's disease: a review and bootstrap analysis.

    PubMed

    Moreno-Martínez, F Javier; Laws, Keith R

    2007-03-01

    There is a consensus that Alzheimer's disease (AD) impairs semantic information, with one of the first markers being anomia i.e. an impaired ability to name items. Doubts remain, however, about whether this naming impairment differentially affects items from the living and nonliving knowledge domains. Most studies have reported an impairment for naming living things (e.g. animals or plants), a minority have found an impairment for nonliving things (e.g. tools or vehicles), and some have found no category-specific effect. A survey of the literature reveals that this lack of agreement may reflect a failure to control for intrinsic variables (such as familiarity) and the problems associated with ceiling effects in the control data. Investigating picture naming in 32 AD patients and 34 elderly controls, we used bootstrap techniques to deal with the abnormal distributions in both groups. Our analyses revealed the previously reported impairment for naming living things in AD patients and that this persisted even when intrinsic variables were covaried; however, covarying control performance eliminated the significant category effect. Indeed, the within-group comparison of living and nonliving naming revealed a larger effect size for controls than patients. We conclude that the category effect in Alzheimer's disease is no larger than is expected in the healthy brain and may even represent a small diminution of the normal profile. PMID:17196316

  13. APOE and APOC1 gene polymorphisms are associated with cognitive impairment progression in Chinese patients with late-onset Alzheimer's disease

    PubMed Central

    Zhou, Qin; Peng, Dantao; Yuan, Xinrui; Lv, Zeping; Pang, Shenghang; Jiang, Wenyu; Yang, Chuyu; Shi, Xiaohong; Pang, Guofang; Yang, Yige; Xie, Haiqun; Zhang, Wandong; Hu, Caiyou; Yang, Ze

    2014-01-01

    Current evidence shows that apolipoprotein E (APOE), apolipoprotein CI (APOC1) and low density lipoprotein receptor-related protein (LRP) variations are related to late-onset Alzheimer's disease. However, it remains unclear if genetic polymorphisms in these genes are associated with cognitive decline in late-onset Alzheimer's disease patients. We performed a 30-month longitudinal cohort study to investigate the relationship between Alzheimer's disease and APOE, APOC1, and LRP. In this study, 78 Chinese Han patients with late-onset Alzheimer's disease were recruited form Guangxi Zhuang Autonomous Region in China. APOE, APOC1, and LRP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphisms. The Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess patients’ cognitive function. After a 30-month follow-up period, we found a significant reduction in Mini-Mental State Examination total score, a higher proportion of patients fulfilling cognitive impairment progression criteria, and a higher proportion of APOC1 H2 carriers in APOE ε4 carriers compared with non-carriers. In addition, the APOE ε4 allele frequency was significantly higher in the cognitive impairment progression group compared with the non-cognitive impairment progression group. In conclusion, APOE ε4 plays an important role in augmenting cognitive decline, and APOC1 H2 may act synergistically with APOE ε4 in increasing the risk of cognitive decline in Chinese patients with late-onset Alzheimer's disease. PMID:25206869

  14. 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

  15. Increased risk of type 2 diabetes in Alzheimer disease.

    PubMed

    Janson, Juliette; Laedtke, Thomas; Parisi, Joseph E; O'Brien, Peter; Petersen, Ronald C; Butler, Peter C

    2004-02-01

    Alzheimer disease and type 2 diabetes are characterized by increased prevalence with aging, a genetic predisposition, and comparable pathological features in the islet and brain (amyloid derived from amyloid beta protein in the brain in Alzheimer disease and islet amyloid derived from islet amyloid polypeptide in the pancreas in type 2 diabetes). Evidence is growing to link precursors of amyloid deposition in the brain and pancreas with the pathogenesis of Alzheimer disease and type 2 diabetes, respectively. Given these similarities, we questioned whether there may be a common underlying mechanism predisposing to islet and cerebral amyloid. To address this, we first examined the prevalence of type 2 diabetes in a community-based controlled study, the Mayo Clinic Alzheimer Disease Patient Registry (ADPR), which follows patients with Alzheimer disease versus control subjects without Alzheimer disease. In addition to this clinical study, we performed a pathological study of autopsy cases from this same community to determine whether there is an increased prevalence of islet amyloid in patients with Alzheimer disease and increased prevalence of cerebral amyloid in patients with type 2 diabetes. Patients who were enrolled in the ADPR (Alzheimer disease n = 100, non-Alzheimer disease control subjects n = 138) were classified according to fasting glucose concentration (FPG) as nondiabetic (FPG <110 mg/dl), impaired fasting glucose (IFG, FPG 110-125 mg/dl), and type 2 diabetes (FPG >126 mg/dl). The mean slope of FPG over 10 years in each case was also compared between Alzheimer disease and non-Alzheimer disease control subjects. Pancreas and brain were examined from autopsy specimens obtained from 105 humans (first, 28 cases of Alzheimer disease disease vs. 21 non-Alzheimer disease control subjects and, second, 35 subjects with type 2 diabetes vs. 21 non-type 2 diabetes control subjects) for the presence of islet and brain amyloid. Both type 2 diabetes (35% vs. 18%; P < 0

  16. [Alzheimer's disease, supporting carers].

    PubMed

    Lottin, Arlette; Botter, René

    2016-03-01

    The association France Alzheimer provides carers with resources. It runs training programmes and organises "Memory Cafes". These initiatives give carers the opportunity to talk about their daily struggles, close to home, and to obtain advice on how to better manage their situation.

  17. 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

  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. Getting lost: directed attention and executive functions in early Alzheimer's disease patients.

    PubMed

    Chiu, Yi-Chen; Algase, Donna; Whall, Ann; Liang, Jersey; Liu, Hsiu-Chih; Lin, Ker-Neng; Wang, Pei-Ning

    2004-01-01

    This study explores the link between directed attention (DA) and getting lost behavior (GLB) in early Alzheimer's disease (AD) using a cross-sectional design with 3 groups. Based on their dementia levels, 116 community-dwelling participants were recruited from a teaching hospital in Taiwan and classified as the non-demented control, questionably demented, and mild AD groups. Statistical analyses include Pearson correlations, one-way ANOVA, and multiple regressions. Attentional impairments, consisting of distractibility, impulsivity, and executive function problems, significantly predict GLB in familiar and unfamiliar environments. Irritability and executive function problems are associated with mental difficulties in choosing a turn, whereas the use of way-finding strategies reduces GLB. Future interventions may include: (a) mental hygiene of aging; (b) programs targeted at improving attentional function and effective way-finding, and (c) inclusion of DA tests in a routine clinical neuropsychological examination for early detection and accurate diagnosis of dementia.

  20. 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).

  1. Knowing about people and naming them: can Alzheimer's disease patients do one without the other?

    PubMed

    Hodges, J R; Greene, J D

    1998-02-01

    It has recently been suggested that patients with semantic breakdown may show the phenomenon of so-called "naming without semantics". If substantiated, this finding would clearly have a major impact on theories of face and object processing, all of which assume that access to semantic knowledge is a prerequisite for successful naming. In order to investigate this issue, we studied recognition, identification (the ability to provide accurate information), and naming of 50 famous faces by 24 patients with mild to moderate dementia of Alzheimer type (DAT) and 30 age-matched controls. The DAT group was impaired in all three conditions. An analysis of the concordance between identification and naming by each patient, for each stimulus item, established that naming a famous face was possible only with semantic knowledge sufficient to identify the person. Our data support the hypothesis that naming is not possible unless semantic information associated with the target is available. Naming without semantics, therefore, did not occur in patients with DAT. By contrast, there were 206 instances (17% of the total responses) in which the patients were able to provide detailed, accurate identifying information yet were unable to name the person represented. The implication of these findings for models of face identification and naming are discussed.

  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. 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.

  4. 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.

  5. Alzheimer's Disease and the Eye☆

    PubMed Central

    Armstrong, Richard A.

    2010-01-01

    Dementia, including Alzheimer's disease (AD), is a major disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of β-amyloid (Aβ) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary response to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances of complex visual functions such as reading, visuospatial function, and in the naming and identification of objects. Many of these changes are controversial with conflicting data in the literature and no ocular or visual feature can be regarded as particularly diagnostic of AD. In addition, some pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. The optometrist has a role in helping a patient with AD, if it is believed that signs and symptoms of the disease are present, so as to optimize visual function and improve the quality of life.

  6. Cognitive intervention in Alzheimer disease.

    PubMed

    Buschert, Verena; Bokde, Arun L W; Hampel, Harald

    2010-09-01

    Alzheimer disease (AD) is one of the most prevalent chronic medical conditions affecting the elderly population. The effectiveness of approved antidementia drugs, however, is limited-licensed AD medications provide only moderate relief of clinical symptoms. Cognitive intervention is a noninvasive therapy that could aid prevention and treatment of AD. Data suggest that specifically designed cognitive interventions could impart therapeutic benefits to patients with AD that are associated with substantial biological changes within the brain. Moreover, evidence indicates that a combination of pharmacological and non-pharmacological interventions could provide greater relief of clinical symptoms than either intervention given alone. Functional and structural MRI studies have increased our understanding of the underlying neurobiological mechanisms of aging and neurodegeneration, but the use of neuroimaging to investigate the effect of cognitive intervention on the brain remains largely unexplored. This Review provides an overview of the use of cognitive intervention in the healthy elderly population and patients with AD, and summarizes emerging findings that provide evidence for the effectiveness of this approach. Finally, we present recommendations for future research on the use of cognitive interventions in AD and discuss potential effects of this therapy on disease modification.

  7. Glucose Metabolism: A Sweet Relief of Alzheimer's Disease.

    PubMed

    Duran-Aniotz, Claudia; Hetz, Claudio

    2016-09-12

    Patients and individuals at risk for Alzheimer's disease show reduced glucose metabolism in the brain. A new study takes advantage of a fly model of Alzheimer's disease to demonstrate that enhancing glucose uptake in neurons has strong neuroprotective effects involving improved proteostasis. PMID:27623263

  8. 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…

  9. 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…

  10. Anatomical heterogeneity of Alzheimer disease

    PubMed Central

    Noh, Young; Jeon, Seun; Seo, Sang Won; Kim, Geon Ha; Cho, Hanna; Ye, Byoung Seok; Yoon, Cindy W.; Kim, Hee Jin; Chin, Juhee; Park, Kee Hyung; Heilman, Kenneth M.

    2014-01-01

    Objective: Because the signs associated with dementia due to Alzheimer disease (AD) can be heterogeneous, the goal of this study was to use 3-dimensional MRI to examine the various patterns of cortical atrophy that can be associated with dementia of AD type, and to investigate whether AD dementia can be categorized into anatomical subtypes. Methods: High-resolution T1-weighted volumetric MRIs were taken of 152 patients in their earlier stages of AD dementia. The images were processed to measure cortical thickness, and hierarchical agglomerative cluster analysis was performed using Ward's clustering linkage. The identified clusters of patients were compared with an age- and sex-matched control group using a general linear model. Results: There were several distinct patterns of cortical atrophy and the number of patterns varied according to the level of cluster analyses. At the 3-cluster level, patients were divided into (1) bilateral medial temporal–dominant atrophy subtype (n = 52, ∼34.2%), (2) parietal-dominant subtype (n = 28, ∼18.4%) in which the bilateral parietal lobes, the precuneus, along with bilateral dorsolateral frontal lobes, were atrophic, and (3) diffuse atrophy subtype (n = 72, ∼47.4%) in which nearly all association cortices revealed atrophy. These 3 subtypes also differed in their demographic and clinical features. Conclusions: This cluster analysis of cortical thickness of the entire brain showed that AD dementia in the earlier stages can be categorized into various anatomical subtypes, with distinct clinical features. PMID:25344382

  11. 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…

  12. [Alzheimer's disease, caregiving and frailty].

    PubMed

    de Peretti, Eva; Villars, Hélène

    2015-01-01

    Caring for a person with Alzheimer's disease often sees the elderly carer at risk of succumbing to frailty. The chronic stress which comes with this caregiving can lead to physical and emotional exhaustion, for which the physiological reserves of the ageing person may be insufficient. The concept of frailty may help to improve the understanding of this vulnerability.

  13. Modular reorganization of brain resting state networks and its independent validation in Alzheimer's disease patients.

    PubMed

    Chen, Guangyu; Zhang, Hong-Ying; Xie, Chunming; Chen, Gang; Zhang, Zhi-Jun; Teng, Gao-Jun; Li, Shi-Jiang

    2013-01-01

    Previous studies have demonstrated disruption in structural and functional connectivity occurring in the Alzheimer's Disease (AD). However, it is not known how these disruptions alter brain network reorganization. With the modular analysis method of graph theory, and datasets acquired by the resting-state functional connectivity MRI (R-fMRI) method, we investigated and compared the brain organization patterns between the AD group and the cognitively normal control (CN) group. Our main finding is that the largest homotopic module (defined as the insula module) in the CN group was broken down to the pieces in the AD group. Specifically, it was discovered that the eight pairs of the bilateral regions (the opercular part of inferior frontal gyrus, area triangularis, insula, putamen, globus pallidus, transverse temporal gyri, superior temporal gyrus, and superior temporal pole) of the insula module had lost symmetric functional connection properties, and the corresponding gray matter concentration (GMC) was significant lower in AD group. We further quantified the functional connectivity changes with an index (index A) and structural changes with the GMC index in the insula module to demonstrate their great potential as AD biomarkers. We further validated these results with six additional independent datasets (271 subjects in six groups). Our results demonstrated specific underlying structural and functional reorganization from young to old, and for diseased subjects. Further, it is suggested that by combining the structural GMC analysis and functional modular analysis in the insula module, a new biomarker can be developed at the single-subject level.

  14. 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.

  15. 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.

  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. PMID:22939533

  17. Comparison of rate of annual change of mental status score in four independent studies of patients with Alzheimer's disease.

    PubMed

    Katzman, R; Brown, T; Thal, L J; Fuld, P A; Aronson, M; Butters, N; Klauber, M R; Wiederholt, W; Pay, M; Xiong, R B

    1988-09-01

    Longitudinal studies of subjects with autopsy-proven Alzheimer's disease in one skilled nursing home and of clinically diagnosed cases (NINCDS/ADRDA criteria) in three community cohorts are compared with regard to the annual rate of change in the error score of the Blessed information-memory-concentration test (IMC) in which the maximum number of errors possible is 33. The four cohorts differed significantly from each other in regard to age, education, sex, and the degree of dementia as measured by the initial IMC score. Subjects spanned the age range of 52 to 96 years and had 2 to 20 years of education. The rate of change in error score per year was similar whether the initial error score was 0 to 7, 8 to 15, or 16 to 23; however, the rate was reduced when the initial error score was 24 or above, due to a ceiling effect of the test. Among subjects with initial IMC scores less than 24, the annual rate of change varied considerably. However, the mean annual rate of change, 4.4 errors (SD +/- 3.6, SEM +/- 0.3) per year, was independent of residence in a nursing home, location of the study site, and of the patient's sex or education. Of particular importance was the finding that the rate of change in mental test score was independent of age. It can be concluded that the rate of cognitive deterioration in patients with Alzheimer's disease is quite variable among individuals and is independent of the patient's age and whether the patient resides in the community or in a nursing home.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Effects of Gingko biloba supplementation in Alzheimer's disease patients receiving cholinesterase inhibitors: data from the ICTUS study.

    PubMed

    Canevelli, Marco; Adali, Nawal; Kelaiditi, Eirini; Cantet, Christelle; Ousset, Pierre-Jean; Cesari, Matteo

    2014-05-15

    Ginkgo biloba (Gb) is currently the most investigated and adopted herbal remedy for cognitive disorders and Alzheimer's disease (AD). Nevertheless, its efficacy in the prevention and treatment of dementia still remains controversial. Specifically, the added effects of Gb in subjects already receiving "conventional" anti-dementia treatments have been to date very scarcely investigated. We evaluated whether the use of Gb is associated with additional cognitive and functional benefit in AD patients already in treatment with cholinesterase inhibitors (ChEIs). Data are from mild to moderate AD patients under ChEI treatment recruited in the Impact of Cholinergic Treatment USe (ICTUS) study. Mixed model analyses were performed to measure six-monthly modifications in the Mini Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score, and the Activities of Daily Living (ADL) scale over a follow-up of 1 year according to the additional Gb supplementation. A total of 828 subjects were considered for the present analyses. Significantly different modifications at the MMSE score over the 12-month follow-up were reported between patients on combined therapy compared to those only taking ChEIs. On the contrary, the modification of the ADAS-Cog score between the two groups did not show statistically significant differences, although similar trends were noticed. No significant modifications of the two adopted outcome measures were observed at the mid-term 6-month evaluation. The modifications over time of the ADL score did not show statistically significant differences between the two groups of interest. Our findings suggest that Gb may provide some added cognitive benefits in AD patients already under ChEIs treatment. The clinical meaningfulness of such effects remains to be confirmed and clarified.

  19. 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.

  20. Clinical Genetics of Alzheimer's Disease

    PubMed Central

    Zou, Zhangyu; Liu, Changyun; Che, Chunhui; Huang, Huapin

    2014-01-01

    Alzheimer's disease (AD) is the most common progressive neurodegenerative disease and the most common form of dementia in the elderly. It is a complex disorder with environmental and genetic components. There are two major types of AD, early onset and the more common late onset. The genetics of early-onset AD are largely understood with mutations in three different genes leading to the disease. In contrast, while susceptibility loci and alleles associated with late-onset AD have been identified using genetic 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 AD, the clinical features of EOAD according to genotypes, and the clinical implications of the genetics of AD. PMID:24955352

  1. Inflammatory process in Alzheimer's Disease

    PubMed Central

    Meraz-Ríos, Marco A.; Toral-Rios, Danira; Franco-Bocanegra, Diana; Villeda-Hernández, Juana; Campos-Peña, Victoria

    2013-01-01

    Alzheimer Disease (AD) is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence of two major hallmarks, the intracellular neurofibrillary tangles (NFTs) and extracellular neuritic plaques (NPs) surrounded by activated astrocytes and microglia. NFTs consist of paired helical filaments of truncated tau protein that is abnormally hyperphosphorylated. The main component in the NP is the amyloid-β peptide (Aβ), a small fragment of 40–42 amino acids with a molecular weight of 4 kD. It has been proposed that the amyloid aggregates and microglia activation are able to favor the neurodegenerative process observed in AD patients. However, the role of inflammation in AD is controversial, because in early stages the inflammation could have a beneficial role in the pathology, since it has been thought that the microglia and astrocytes activated could be involved in Aβ clearance. Nevertheless the chronic activation of the microglia has been related with an increase of Aβ and possibly with tau phosphorylation. Studies in AD brains have shown an upregulation of complement molecules, pro-inflammatory cytokines, acute phase reactants and other inflammatory mediators that could contribute with the neurodegenerative process. Clinical trials and animal models with non-steroidal anti-inflammatory drugs (NSAIDs) indicate that these drugs may decrease the risk of developing AD and apparently reduce Aβ deposition. Finally, further studies are needed to determine whether treatment with anti-inflammatory strategies, may decrease the neurodegenerative process that affects these patients. PMID:23964211

  2. 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

  3. Low-Dose Atypical Antipsychotic Risperidone Improves the 5-Year Outcome in Alzheimer's Disease Patients with Sleep Disturbances.

    PubMed

    Yin, You; Liu, Yan; Zhuang, Jianhua; Pan, Xiao; Li, Peng; Yang, Yuechang; Li, Yan-Peng; Zhao, Zheng-Qing; Huang, Liu-Qing; Zhao, Zhong-Xin

    2015-01-01

    Sleep disturbances (SD) accelerate the progression of Alzheimer's disease (AD) and increase the stress of caregivers. However, the long-term outcome of disturbed nocturnal sleep/wake patterns in AD and on increased stress of spousal caregivers is unclear. This study assessed the 5-year effect of nocturnal SD on the long-term outcome in AD patients. A total of 156 donepezil-treated mild-moderate AD patients (93 AD + SD and 63 AD - SD as a control group) were recruited. The AD + SD patients were formed into 4 subgroups according to the preferences of spousal caregivers for treatment with atypical antipsychotics (0.5-1 mg risperidone, n = 22), non-benzodiazepine hypnotic (5-10 mg zolpidem tartrate, n = 33), melatonin (2.55 mg, n = 9), or no-drug treatment (n = 29). SD were evaluated by polysomnography, sleep scale, and cognitive scale examinations. Moreover, all spousal caregivers of AD patients were assessed using a series of scales, including sleep, anxiety, mood, and treatment attitude scales. Our data showed that nocturnal sleep/wake disturbances were significantly associated with lower 5-year outcomes for AD patients, earlier nursing home placement, and more negative emotions of spousal caregivers. Treatment with low-dose atypical antipsychotic risperidone improved the 5-year outcome in AD + SD patients. In conclusion, low-dose atypical antipsychotic risperidone improves the 5-year outcome in AD patients with SD. Moreover, improvement of nocturnal sleep problems in AD patients will also bring better emotional stability for AD caregivers.

  4. 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

  5. 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. PMID:26711459

  6. 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.

  7. Word-stem priming and recognition in type 2 diabetes mellitus, Alzheimer's disease patients and healthy older adults.

    PubMed

    Redondo, María Teresa; Beltrán-Brotóns, José Luís; Reales, José Manuel; Ballesteros, Soledad

    2015-11-01

    The present study investigated (a) whether the pattern of performance on implicit and explicit memory of patients with type 2 diabetes mellitus (DM2) is more similar to those of patients with Alzheimer's disease (AD) or to cognitively normal older adults and (b) whether glycosylated hemoglobin levels (a measure of glucose regulation) are related to performance on the two memory tasks, implicit word-stem completion and "old-new" recognition. The procedures of both memory tasks included encoding and memory test phases separated by a short delay. Three groups of participants (healthy older adults, DM2 patients and AD patients) completed medical and psychological assessments and performed both memory tasks on a computer. The results of the word-stem completion task showed similar implicit memory in the three groups. By contrast, explicit recognition of the three groups differed. Implicit memory was not affected by either normal or pathological aging, but explicit memory deteriorated in the two groups of patients, especially in AD patients, showing a severe impairment compared to the cognitively healthy older adults. Importantly, glycosylated hemoglobin levels were not related to performance on either implicit or explicit memory tasks. These findings revealed a clear dissociation between explicit and implicit memory tasks in normal and pathological aging. Neuropsychologists and clinicians working with TM2 patients should be aware that the decline of voluntary, long-term explicit memory could have a negative impact on their treatment management. By contrast, the intact implicit memory of the two clinical groups could be used in rehabilitation.

  8. Using mental imagery to improve memory in patients with Alzheimer's disease: Trouble generating or remembering the mind's eye?

    PubMed Central

    Hussey, Erin; Smolinsky, John G.; Piryatinsky, Irene; Budson, Andrew E.; Ally, Brandon A.

    2011-01-01

    The present investigation worked to understand whether patients with mild Alzheimer's disease (AD) could use general or self-referential mental imagery to improve their recognition of visually presented words. Experiment 1 showed that, unlike healthy controls, patients generally did not benefit from either type of imagery. To help determine whether the patients' inability to benefit from mental imagery at encoding was due to poor memory or due to an impairment in mental imagery, subjects then performed four imagery tasks, with varying imagery and cognitive demands. Experiment 2 showed that patients successfully performed basic visual imagery, but degraded semantic memory, coupled with visuospatial and executive functioning deficits, impaired their ability to perform more complex types of imagery. Given that patients with AD can perform basic mental imagery, our results suggest that episodic memory deficits likely prevent AD patients from storing or retrieving general mental images generated during encoding. Overall, the results of both experiments suggest that neurocognitive deficits do not allow patients with AD to perform complex mental imagery, which may be most beneficial to improving memory. However, our data also suggest that intact basic mental imagery and rehearsal could possibly be helpful if used in a rehabilitation multi-session intervention approach. PMID:21946012

  9. 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

    2013-12-01

    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.

  10. 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.

  11. 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.

  12. Socio-economic Aspects of Alzheimer's Disease.

    PubMed

    Marešová, Petra; Mohelská, Hana; Dolejš, Josef; Kuča, Kamil

    2015-01-01

    Social development, better living conditions and medical advances lead to the fact that more people have the opportunity to live longer than in the past. The aging population is a characteristic feature of demographic trends in developed countries. This trend is closely linked with the issue of increasing number of diseases in old age and increasing government expenditure on health and social care. The most frequently mentioned diseases in old age include dementia. The cause may lie in all kinds of diseases, the most common are Alzheimer's disease and cerebrovascular disease. Now the care of current 35 million patients with dementia costs over $ 600 billion per year, it is approximately one percent of global Gross Domestic Product. This review discusses the recent issues and questions in the area of social and economic aspects of Alzheimer's disease. It focuses in detail on the national strategies in the approach to Alzheimer's disease, the anticipated problems concerning the insufficient number of social workers and necessary expenses of state budgets in the future. The situation in the area of health insurance companies' expenditures is illustrated in the context of the analysis of long-term care systems, in the chosen countries within the European Union. PMID:26510983

  13. 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.

  14. 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.

  15. 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.

  16. 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

  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. PMID:26801955

  18. [Truth telling of Alzheimer's disease diagnosis].

    PubMed

    Fuentes R, Paola; Prato, Juan Andrés

    2012-06-01

    Alzheimer's disease is becoming an increasingly common problem due to population aging. Most of the research on truth telling in relation to diagnosis has been done in oncology. However, although growing, there has a lack of interest about attitudes held among physicians towards disclosing the diagnosis of Alzheimer's disease. Physicians, family caregivers and patients have different views about it. The reasons most often given for communicating the diagnosis are the right to know, relief of anxiety to know the cause of memory problems, early access to treatment and ability to plan ahead. On the contrary, the reasons for concealing the diagnosis are based on the right not to know, the anxiety associated to knowing the diagnosis and the absence of curative therapies for the disease. The aim of this paper is to report the current state of literature on diagnostic truth telling in dementia, review the ethical principles involved, and finally give a strategy to address the issue.

  19. Cognitive rehabilitation in Alzheimer's Disease.

    PubMed

    Cotelli, Maria; Calabria, Marco; Zanetti, Orazio

    2006-04-01

    Non-pharmacological treatment in Alzheimer's Disease has gained great attention in recent years. The limited efficacy of drug therapy and the plasticity of human central nervous system are the two main reasons that explain this growing interest in rehabilitation. Different approaches have been developed. Here we discuss the efficacy of non-pharmacological therapy in the frame of two main approaches: Multistrategy Approaches (Reality Orientation, Reminiscence Therapy and Validation Therapy) and Cognitive Methods.

  20. Midlife predictors of Alzheimer's disease

    PubMed Central

    Bendlin, B. B.; Carlsson, C. M.; Gleason, C. E.; Johnson, S. C.; Sodhi, A.; Gallagher, C.L.; Puglielli, L.; Engelman, C. D.; Ries, M. L.; Xu, G.; Wharton, W.; Asthana, S.

    2010-01-01

    Factors contributing to increased risk for Alzheimer's disease (AD) include age, sex, genes, and family history of AD. Several risk factors for AD are endogenous; however accumulating evidence implicates modifiable risk factors in the pathogenesis of AD. Although the continued task of identifying new genes will be critical to learning more about the disease, several research findings suggest that potentially alterable environmental factors influence genetic contributions, providing targets for disease prevention and treatment. Here, we review midlife risk factors for AD, and address the potential for therapeutic intervention in midlife. PMID:20044221

  1. 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.

  2. [Neuropsychiatric and behavioral symptomatology in Alzheimer disease].

    PubMed

    García-Alberca, J M; Lara Muñoz, J P; Berthier Torres, M

    2010-01-01

    Patients with Alzheimer's disease (AD) show high incidence of behavioral and psychological symptoms (BPS).The occurrence of BPS has a great impact on the patients and caregiver's quality of life, increases caregiver's burden, and in many cases precipitates admission of the patients to a geriatric center. On the other hand, the importance of the BPS is increasing because most of them are susceptible to being treated effectively, mainly thanks to the use of drug measures and behaviour modification techniques. This study describes the pathophysiological mechanisms of BPS in AD and its relationship with cognitive and functional impairment of patient and caregiver's burden and current therapies.

  3. Discrepancies regarding the quality of life of patients with Alzheimer's disease: a three-year longitudinal study.

    PubMed

    Conde-Sala, Josep L; Turró-Garriga, Oriol; Garre-Olmo, Josep; Vilalta-Franch, Joan; Lopez-Pousa, Secundino

    2014-01-01

    Cross-sectional studies report notable discrepancies between patient and caregiver ratings of the quality of life of patients (QoL-p) with Alzheimer's disease (AD). This study aimed to identify the factors associated with any changes in QoL-p ratings and any discrepancies between patient and caregiver ratings of QoL-p. Three-year follow-up of a cohort of non-institutionalized patients (n = 119). QoL-p was assessed by the Quality of Life in AD (QoL-AD) scale. We analyzed the influence of functional and cognitive status and behavioral problems in patients, and burden and mental health in caregivers. Repeated measures analysis was applied to the scores of patients and caregivers on the QoL-AD, and to the discrepancies between them. Generally, patients' own ratings remained stable over time (F3,116 = 0.9, p = 0.439), whereas caregiver ratings showed a decline (F3,116 = 9.4, p < 0.001). In the analysis of discrepancies, patients with anosognosia gave higher ratings (F1,117 = 11.9, p = 0.001), whereas caregiver ratings were lower when the patient showed greater agitation (F1,117 = 13.0, p < 0.001), apathy (F1,117 = 15.4, p < 0.001), and disabilities (F1,117 = 17.1, p < 0.001), and when the caregiver experienced greater burden (F1,117 = 9.0, p = 0.003) and worse mental health (F1,117 = 10.1, p = 0.003). Patient ratings of QoL-p remain generally stable over time, whereas those of caregivers show a decline, there being significant discrepancies in relation to specific patient and caregiver factors.

  4. 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.

  5. 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.

  6. 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. PMID:26559259

  7. 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. PMID:24535580

  8. 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.

  9. 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.

  10. 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. PMID:27160819

  11. Alzheimer's Disease Facts and Figures

    MedlinePlus

    ... prevented, cured or even slowed. Invest in a world without Alzheimer's. Donate Caregivers In 2015, 15.9 ... Association ® . All rights reserved. Our vision is a world without Alzheimer's Formed in 1980, the Alzheimer's Association ...

  12. Imaging the earliest stages of Alzheimer's disease.

    PubMed

    Wu, William; Small, Scott A

    2006-12-01

    Historical progress in medicine can be charted along the lines of technical innovations that have visualized the invisible. One hundred years ago, Alois Alzheimer exploited newly developed histological stains to visualize his eponymonous disease in dead tissue under the microscope. Now, as we are entering the second century of Alzheimer's disease research, technical innovation has endowed us with a range of in vivo imaging techniques that promise to visualize Alzheimer' disease in living people. The earliest stage of Alzheimer's disease is characterized by cell-sickness, not cell-death, and can occur before the deposition of amyloid plaques or neurofibrillary tangles. In principle, 'functional' imaging techniques might be able to detect this early stage of the disease, a stage that was invisible to Alzheimer himself. Here, we will first define the neurobiological meaning of 'function' and then review the different approaches that measure brain dysfunction in Alzheimer' disease.

  13. Hallucinations and sleep-wake cycle in Alzheimer's disease: a questionnaire-based study in 218 patients.

    PubMed

    Sinforiani, E; Terzaghi, M; Pasotti, C; Zucchella, C; Zambrelli, E; Manni, R

    2007-04-01

    The aim was to evaluate the relationship between hallucinations and the sleep-wake cycle in a sample of Alzheimer's disease (AD) patients in the early-moderate stage. Two hundred and eighteen AD patients (66 males, 152 females, mean age 74.3+/-6.85) were administered a sleep questionnaire in the presence of a care-giver. Twenty-six out of 218 (12%) reported the occurrence of hallucinations, mainly visual. In 18/28 (69%) hallucinations occurred when the patient was awake and in 8 (31%) hallucinations were reported to occur close to a specific phase of the sleep-wake cycle. Vivid dreams were reported in 25/218 (11%) and violent sleep-related and dream-related behaviours (probable REM behaviour episodes) in 22/218 (10%). Both REM phenomena were more frequent in AD hallucinators than in AD non-hallucinators (26.9% vs. 9.3%, and 26.9% vs. 7.8%, p<0.007). Our data indicate a lower incidence of hallucinations and presumable REM behaviour disorder (RBD) in AD, at least in the early-moderate phase, than that observed in synucleinopathies. However, the higher occurrence of vivid dreams and RBD in AD patients with hallucinations compared to those without hallucinations indicates a potential role of disordered REM sleep in influencing the occurrence of hallucinations in AD, similar to what has been observed in synucleinopathies.

  14. 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.

  15. 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.

  16. Fusing Heterogeneous Data for Alzheimer's Disease Classification.

    PubMed

    Pillai, Parvathy Sudhir; Leong, Tze-Yun

    2015-01-01

    In multi-view learning, multimodal representations of a real world object or situation are integrated to learn its overall picture. Feature sets from distinct data sources carry different, yet complementary, information which, if analysed together, usually yield better insights and more accurate results. Neuro-degenerative disorders such as dementia are characterized by changes in multiple biomarkers. This work combines the features from neuroimaging and cerebrospinal fluid studies to distinguish Alzheimer's disease patients from healthy subjects. We apply statistical data fusion techniques on 101 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We examine whether fusion of biomarkers helps to improve diagnostic accuracy and how the methods compare against each other for this problem. Our results indicate that multimodal data fusion improves classification accuracy. PMID:26262148

  17. Memory evaluation with a new cued recall test in patients with mild cognitive impairment and Alzheimer's disease.

    PubMed

    Ivanoiu, Adrian; Adam, Stephane; Van der Linden, Martial; Salmon, Eric; Juillerat, Anne-Claude; Mulligan, Reinhild; Seron, Xavier

    2005-01-01

    Free delayed recall is considered the memory measure with the greatest sensitivity for the early diagnosis of dementia. However, its specificity for dementia could be lower, as deficits other than those of pure memory might account for poor performance in this difficult and effortful task. Cued recall is supposed to allow a better distinction between poor memory due to concurrent factors and impairments related to the neurodegenerative process. The available cued recall tests suffer from a ceiling effect. This is a prospective, longitudinal study aiming to assess the utility of a new memory test based on cued recall that avoids the ceiling effect in the early diagnosis of Alzheimer's disease (AD). Twenty-five patients with mild cognitive impairment (MCI), 22 probable AD patients (NINCDS-ADRDA) at a mild stage, 22 elderly patients with subjective memory complaints (SMC) and 38 normal age-matched controls took part in the study. The patients underwent a thorough cognitive evaluation and the recommended screening procedure for the diagnosis of dementia. All patients were re-examined 12-18 months later. A newly devised delayed cued recall test using semantic cues (The RI48 Test) was compared with three established memory tests: the Ten Word-List Recall from CERAD, the "Doors" and the "Shapes" Tests from "The Doors and People Test Battery". Forty-four % of the MCI patients fulfilled criteria for probable AD at follow-up. The RI48 Test classified correctly 88% of the MCI and SMC participants and was the best predictor of the status of MCI and mild AD as well as the outcome of the MCI patients. Poor visual memory was the second best predictor of those MCI patients who evolved to AD. A cued recall test which avoids the ceiling effect is at least as good as the delayed free recall tests in the early detection of AD. PMID:15654553

  18. Visual exploration behaviour during clock reading in Alzheimer's disease.

    PubMed

    Mosimann, U P; Felblinger, J; Ballinari, P; Hess, C W; Müri, R M

    2004-02-01

    Eye movement behaviour during visual exploration of 24 patients with probable Alzheimer's disease and 24 age-matched controls was compared in a clock reading task. Controls were found to focus exploration on distinct areas at the end of each clock hand. The sum of these two areas of highest fixation density was defined as the informative region of interest (ROI). In Alzheimer's disease patients, visual exploration was less focused, with fewer fixations inside the ROI, and the time until the first fixation was inside the ROI was significantly delayed. Changes of fixation distribution correlated significantly with the ability to read the clock correctly, but did not correlate with dementia severity. In Alzheimer's disease patients, fixations were longer and saccade amplitudes were smaller. The altered visual exploration in Alzheimer's disease might be related to parietal dysfunction or to an imbalance between a degraded occipito-parietal and relatively preserved occipito-temporal visual network. PMID:14691059

  19. 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

  20. Relationship of aluminum to Alzheimer's disease.

    PubMed

    Perl, D P

    1985-11-01

    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.

  1. Cajal's contributions to the study of Alzheimer's disease.

    PubMed

    García-Marín, Virginia; García-López, Pablo; Freire, Miguel

    2007-09-01

    Last year 2006, we commemorated two important events in the history of Neuroscience. One hundred years ago, on November 3, Alois Alzheimer (1864-1915) presented the first case of a patient with symptoms of a disease that later would be called Alzheimer's disease. One month later, on December 10, Santiago Ramón y Cajal (1852-1934) and Camilo Golgi (1843-1926) received the Nobel Prize "in recognition of their work on the structure of the Nervous System". These facts seem not to be related, but working in the Museum Cajal we found 37 histological preparations of material from patients suffering from Alzheimer's disease, revealing that Cajal also studied this disease. This paper deals with Cajal's contribution to the study of Alzheimer's disease and it is fully illustrated by original pictures of Cajal's slides preserved in the Cajal Museum, Madrid.

  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. PMID:27159982

  3. [On the 100th anniversary of Alzheimer's disease].

    PubMed

    Verhey, F R J

    2006-12-30

    In November 1906, the German neurologist Alois Alzheimer presented a lecture to his colleagues regarding a 55-year-old patient with dementia who was found to have aggregated protein deposits (senile plaques) and abnormal neurofibrils in the cerebral cortex. Alzheimer was born in 1864 in Bavaria. After he became financially independent through marriage, he could devote himself to neuropathological research. At the end of the 19th century, it was widely believed that dementia was the inevitable consequence of arteriosclerosis. Alzheimer questioned this belief after finding no postmortem evidence of arteriosclerotic vessel alterations in the brain of a young patient with dementia. After finding a second and third case, Alzheimer was convinced that he was on the verge of discovering a new disease. The eponym 'Alzheimer's disease' was introduced in 1910 by his mentor Kraepelin.

  4. 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

  5. Gait and balance analysis for patients with Alzheimer's disease using an inertial-sensor-based wearable instrument.

    PubMed

    Hsu, Yu-Liang; Chung, Pau-Choo Julia; Wang, Wei-Hsin; Pai, Ming-Chyi; Wang, Chun-Yao; Lin, Chien-Wen; Wu, Hao-Li; Wang, Jeen-Shing

    2014-11-01

    Despite patients with Alzheimer's disease (AD) were reported of revealing gait disorders and balance problems, there is still lack of objective quantitative measurement of gait patterns and balance capability of AD patients. Based on an inertial-sensor-based wearable device, this paper develops gait and balance analyzing algorithms to obtain quantitative measurements and explores the essential indicators from the measurements for AD diagnosis. The gait analyzing algorithm is composed of stride detection followed by gait cycle decomposition so that gait parameters are developed from the decomposed gait details. On the other hand, the balance is measured by the sway speed in anterior-posterior (AP) and medial-lateral (ML) directions of the projection path of body's center of mass (COM). These devised gait and balance parameters were explored on twenty-one AD patients and fifty healthy controls (HCs). Special evaluation procedure including single-task and dual-task walking experiments for observing the cognitive function and attention is also devised for the comparison of AD and HC groups. Experimental results show that the wearable instrument with the designed gait and balance analyzing system is a promising tool for automatically analyzing gait information and balance ability, serving as assistant indicators for early diagnosis of AD.

  6. Improvement of memory recall by quercetin in rodent contextual fear conditioning and human early-stage Alzheimer's disease patients.

    PubMed

    Nakagawa, Toshiyuki; Itoh, Masanori; Ohta, Kazunori; Hayashi, Yuichi; Hayakawa, Miki; Yamada, Yasushi; Akanabe, Hiroshi; Chikaishi, Tokio; Nakagawa, Kiyomi; Itoh, Yoshinori; Muro, Takato; Yanagida, Daisuke; Nakabayashi, Ryo; Mori, Tetsuya; Saito, Kazuki; Ohzawa, Kaori; Suzuki, Chihiro; Li, Shimo; Ueda, Masashi; Wang, Miao-Xing; Nishida, Emika; Islam, Saiful; Tana; Kobori, Masuko; Inuzuka, Takashi

    2016-06-15

    Patients with Alzheimer's disease (AD) experience a wide array of cognitive deficits, which typically include the impairment of explicit memory. In previous studies, the authors reported that a flavonoid, quercetin, reduces the expression of ATF4 and delays memory deterioration in an early-stage AD mouse model. In the present study, the effects of long-term quercetin intake on memory recall were assessed using contextual fear conditioning in aged wild-type mice. In addition, the present study examined whether memory recall was affected by the intake of quercetin-rich onion (a new cultivar of hybrid onion 'Quergold') powder in early-stage AD patients. In-vivo analysis indicated that memory recall was enhanced in aged mice fed a quercetin-containing diet. Memory recall in early-stage AD patients, determined using the Revised Hasegawa Dementia Scale, was significantly improved by the intake of quercetin-rich onion (Quergold) powder for 4 weeks compared with the intake of control onion ('Mashiro' white onion) powder. These results indicate that quercetin might influence memory recall. PMID:27145228

  7. 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.

  8. 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)

  9. An Attenuation of the "Normal" Category Effect in Patients with Alzheimer's Disease: A Review and Bootstrap Analysis

    ERIC Educational Resources Information Center

    Moreno-Martinez, F. Javier; Laws, Kieth R.

    2007-01-01

    There is a consensus that Alzheimer's disease (AD) impairs semantic information, with one of the first markers being anomia i.e. an impaired ability to name items. Doubts remain, however, about whether this naming impairment differentially affects items from the living and nonliving knowledge domains. Most studies have reported an impairment for…

  10. 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…

  11. Word-stem priming and recognition in type 2 diabetes mellitus, Alzheimer's disease patients and healthy older adults.

    PubMed

    Redondo, María Teresa; Beltrán-Brotóns, José Luís; Reales, José Manuel; Ballesteros, Soledad

    2015-11-01

    The present study investigated (a) whether the pattern of performance on implicit and explicit memory of patients with type 2 diabetes mellitus (DM2) is more similar to those of patients with Alzheimer's disease (AD) or to cognitively normal older adults and (b) whether glycosylated hemoglobin levels (a measure of glucose regulation) are related to performance on the two memory tasks, implicit word-stem completion and "old-new" recognition. The procedures of both memory tasks included encoding and memory test phases separated by a short delay. Three groups of participants (healthy older adults, DM2 patients and AD patients) completed medical and psychological assessments and performed both memory tasks on a computer. The results of the word-stem completion task showed similar implicit memory in the three groups. By contrast, explicit recognition of the three groups differed. Implicit memory was not affected by either normal or pathological aging, but explicit memory deteriorated in the two groups of patients, especially in AD patients, showing a severe impairment compared to the cognitively healthy older adults. Importantly, glycosylated hemoglobin levels were not related to performance on either implicit or explicit memory tasks. These findings revealed a clear dissociation between explicit and implicit memory tasks in normal and pathological aging. Neuropsychologists and clinicians working with TM2 patients should be aware that the decline of voluntary, long-term explicit memory could have a negative impact on their treatment management. By contrast, the intact implicit memory of the two clinical groups could be used in rehabilitation. PMID:26253308

  12. 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.

  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. The cholinergic hypothesis of Alzheimer's disease: a review of progress

    PubMed Central

    Francis, P.; Palmer, A.; Snape, M.; Wilcock, G.

    1999-01-01

    Alzheimer's disease is one of the most common causes of mental deterioration in elderly people, accounting for around 50%-60% of the overall cases of dementia among persons over 65 years of age. The past two decades have witnessed a considerable research effort directed towards discovering the cause of Alzheimer's disease with the ultimate hope of developing safe and effective pharmacological treatments. This article examines the existing scientific applicability of the original cholinergic hypothesis of Alzheimer's disease by describing the biochemical and histopathological changes of neurotransmitter markers that occur in the brains of patients with Alzheimer's disease both at postmortem and neurosurgical cerebral biopsy and the behavioural consequences of cholinomimetic drugs and cholinergic lesions. Such studies have resulted in the discovery of an association between a decline in learning and memory, and a deficit in excitatory amino acid (EAA) neurotransmission, together with important roles for the cholinergic system in attentional processing and as a modulator of EAA neurotransmission. Accordingly, although there is presently no "cure" for Alzheimer's disease, a large number of potential therapeutic interventions have emerged that are designed to correct loss of presynaptic cholinergic function. A few of these compounds have confirmed efficacy in delaying the deterioration of symptoms of Alzheimer's disease, a valuable treatment target considering the progressive nature of the disease. Indeed, three compounds have received European approval for the treatment of the cognitive symptoms of Alzheimer's disease, first tacrine and more recently, donepezil and rivastigmine, all of which are cholinesterase inhibitors.

 PMID:10071091

  15. 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.

  16. 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

    2015-01-01

    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. PMID:26836011

  17. Alzheimer's Disease and Medicinal Plants: An Overview.

    PubMed

    Manoharan, S; Essa, M Mohamed; Vinoth, A; Kowsalya, R; Manimaran, A; Selvasundaram, R

    2016-01-01

    Alzheimer's disease (AD) is progressive neurodegenerative disorder and identified as a major health concern globally. Individuals with AD and their care givers are affected in personal, emotional, financial, and social levels. Due to its significant impact and heavy burden on the individual, the patients' families, and society, it is highly needed to search for cost effective, long-time retention therapeutic targets. In recent decades, there are lots of research conducted the possible benefit of natural products and their active components on AD and other neurodegenerative disease, which are discussed here. PMID:27651250

  18. Early neuroimaging diagnosis of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Jiao, Jianling; Liu, Timon C.; Li, Yan; Liu, Songhao

    2002-04-01

    Neuroimaging has played an important role in evaluating the Alzheimer's disease (AD) patients, and its uses are growing. Magnetic resonance imaging (MRI) may show the presence of cerebral infarcts and white matter disease. Single photon emission computed tomography (SPECT) and positron emission tomography (PET), which visualize such cerebral functions as glucose metabolism and blood flow, may provide positive evidence to support the diagnosis of AD. Electrical impedance tomography (EIT) is a recently developed technique which enables the internal impedance of an object to be imaged noninvasively.

  19. Is aging part of Alzheimer's disease, or is Alzheimer's disease part of aging?

    PubMed

    Swerdlow, Russell H

    2007-10-01

    For 70 years after Alois Alzheimer described a disorder of tangle-and-plaque dementia, Alzheimer's disease was a condition of the relatively young. Definitions of Alzheimer's disease (AD) have, however, changed over the past 30 years and under the revised view AD has truly become an age-related disease. Most now diagnosed with AD are elderly and would not have been diagnosed with AD as originally conceived. Accordingly, younger patients that qualify for a diagnosis of AD under both original and current Alzheimer's disease constructs now represent an exceptionally small percentage of the diagnosed population. The question of whether pathogenesis of the "early" and "late" onset cases is similar enough to qualify as a single disease was previously raised although not conclusively settled. Interestingly, debate on this issue has not kept pace with advancing knowledge about the molecular, biochemical and clinical underpinnings of tangle-and-plaque dementias. Since the question of whether both forms of AD share a common pathogenesis could profoundly impact diagnostic and treatment development efforts, it seems worthwhile to revisit this debate.

  20. Olfactory dysfunction in Alzheimer's disease.

    PubMed

    Zou, Yong-Ming; Lu, Da; Liu, Li-Ping; Zhang, Hui-Hong; Zhou, Yu-Ying

    2016-01-01

    Alzheimer's disease (AD) is a common neurodegenerative disorder with the earliest clinical symptom of olfactory dysfunction, which is a potential clinical marker for AD severity and progression. However, many questions remain unanswered. This article reviews relevant research on olfactory dysfunction in AD and evaluates the predictive value of olfactory dysfunction for the epidemiological, pathophysiological, and clinical features of AD, as well as for the conversion of cognitive impairment to AD. We summarize problems of existing studies and provide a useful reference for further studies in AD olfactory dysfunction and for clinical applications of olfactory testing. PMID:27143888

  1. Confirmatory population pharmacokinetic analysis for bapineuzumab phase 3 studies in patients with mild to moderate Alzheimer's disease.

    PubMed

    Hu, Chuanpu; Adedokun, Omoniyi; Ito, Kaori; Raje, Sangeeta; Lu, Ming

    2015-02-01

    The population pharmacokinetics of bapineuzumab, a humanized monoclonal IgG1 antibody that was generated from a murine monoclonal antibody and binds specifically to amino acids 1 to 5 of the free N-terminus of human amyloid-beta peptide, were characterized in patients with mild-to-moderate alzheimer's disease in two Phase 3 studies (ELN115727-301 and ELN115727-302). A total of 8,040 serum concentration measurements were analyzed from 1,458 patients who received 6 doses of bapineuzumab intravenously once every 13 weeks. A confirmatory analysis was conducted using a prespecified two-compartment model with first-order elimination. After the primary covariate effect assessment, a reduced model was obtained. Based on the reduced model, the typical population values for clearance (CL) and volume (Vc ) from the central compartment in a Caucasian subject with a standardized body weight of 70 kg were 0.17 L/day and 3.13 L, respectively. Bapineuzumab CL and Vc increased with body weight. Furthermore, CL was 15% higher in non-Caucasian subjects; however, this was not considered clinically relevant. None of the other evaluated covariates had a meaningful impact on CL. The median terminal elimination half-life was estimated to be approximately 29 days. Sensitivity analyses and bootstrapping results supported model stability. PMID:25187399

  2. Targeting therapy for homocysteic acid in the blood represents a potential recovery treatment for cognition in Alzheimer's disease patients

    PubMed Central

    Hasegawa, Tohru; Ukai, Wataru

    2016-01-01

    At present, we have no reliable means of recovering cognitive impairment in Alzheimer's disease (AD) patients. We hypothesized that homocysteic acid (HA) in the blood might represent one such pathogen that could be excreted into the urine. Since DHA is known to reduce circulating levels of homocysteine, and since exercise attenuates this effect, it follows that supplementation of the diet with DHA, along with increased levels of physical activity, may help to reduce cognitive impairment in AD patients. Our hypothesis was proven to be correct because memory problems in 3xTg- AD mice (a model for AD in which animals develop amyloid pathology), and in a mouse model of familial AD, were recovered following treatment with an anti-HA antibody and not by amyloid treatment. Interestingly, 3xTg-AD mice with amyloid pathology showed increased levels of HA level. This could perhaps be explained by the fact that amyloid precursor protein and/or presenilin increases calcium influx, which could then increase levels of superoxide and consequently increase levels of HA from homocysteine or methionine. Our hypothesis is also partially supported by an open clinical trial of certain dietary supplements that has shown impressive results. Also there are other treatments hypothesis which would be possible for the effective therapies, such as ribonucleoprotein therapy, a β-secretase inhibitor treatment and the metabolic enhancement treatment. PMID:27632569

  3. Are there sex differences in emotional and biological responses in spousal caregivers of patients with Alzheimer's disease?

    PubMed

    Thompson, Russel L; Lewis, Sharon L; Murphy, Margaret R; Hale, Jennifer M; Blackwell, Paula H; Acton, Gayle J; Clough, Dorothy H; Patrick, Graham J; Bonner, Peter N

    2004-04-01

    The purpose of this study was to compare emotional and biological responses of men and women who are spousal caregivers of patients with Alzheimer's disease (AD). Quality-of-life measurements, bioinstrumentation data, and immunophenotype assessments were obtained from female and male spousal caregivers of patients with AD. Spousal caregivers (women, n = 45 with average age 69.7; men, n = 16 with average age 71.4 years) completed questionnaires that assessed psychosocial variables. Blood was drawn and lymphocyte subsets (including natural killer [NK] cell number) were determined using flow cytometry. The degree of relaxation was determined measuring muscle tension (EMG) in the frontalis and trapezius muscles, skin conductance, skin temperature, and heart rate. Male spousal caregivers, as compared to female spousal caregivers, had significantly lower levels of stress, depression, caregiver burden (subjective), anxiety, anger-hostility, and somatic symptoms and higher levels of mental health, sense of coherence, NK cell number, and social and physical functioning. There were no statistically significant differences between the 2 groups in social support, coping resources, or T, T suppressor, or activated T cells. Women had more T helper cells and fewer NK cells than men. Men had fewer manifestations of a physiological stress response, as indicated by bioinstrumentation parameters. Unique sex-specific issues need to be considered when strategies are implemented to assist the increasing number of caregivers as our society ages.

  4. The rationale for deep brain stimulation in Alzheimer's disease.

    PubMed

    Mirzadeh, Zaman; Bari, Ausaf; Lozano, Andres M

    2016-07-01

    Alzheimer's disease is a major worldwide health problem with no effective therapy. Deep brain stimulation (DBS) has emerged as a useful therapy for certain movement disorders and is increasingly being investigated for treatment of other neural circuit disorders. Here we review the rationale for investigating DBS as a therapy for Alzheimer's disease. Phase I clinical trials of DBS targeting memory circuits in Alzheimer's disease patients have shown promising results in clinical assessments of cognitive function, neurophysiological tests of cortical glucose metabolism, and neuroanatomical volumetric measurements showing reduced rates of atrophy. These findings have been supported by animal studies, where electrical stimulation of multiple nodes within the memory circuit have shown neuroplasticity through stimulation-enhanced hippocampal neurogenesis and improved performance in memory tasks. The precise mechanisms by which DBS may enhance memory and cognitive functions in Alzheimer's disease patients and the degree of its clinical efficacy continue to be examined in ongoing clinical trials.

  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. Pittsburgh compound B-negative dementia: a possibility of misdiagnosis of patients with non-alzheimer disease-type dementia as having AD.

    PubMed

    Shimada, Hiroyuki; Ataka, Suzuka; Takeuchi, Jun; Mori, Hiroshi; Wada, Yasuhiro; Watanabe, Yasuyoshi; Miki, Takami

    2011-09-01

    Amyloid imaging has been used to detect amyloid deposition in the brain. We performed Pittsburgh compound B (PiB)-positron emission tomography on 63 patients with dementia having cognitive decline or memory disturbance. In addition, we measured the patients' apolipoprotein E4 (apo E4) status and cerebrospinal fluid (CSF) levels of amyloid-β (Aβ)1-42, tau, and P-tau. Finally, the patients were diagnosed as having probable Alzheimer disease (AD) on the basis of their neuropsychological findings and because they met the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria. Among the patients diagnosed with probable AD, 10 patients were PiB negative. The CSF levels of P-tau and tau in PiB-negative patients were significantly lower than those in the PiB-positive patients. In addition, the CSF levels of Aβ1-42 in the PiB-negative patients were significantly higher than those in the PiB-positive patients. None of the PiB-negative patients were apo E4 carriers. These results suggest that the PiB-negative patient group included not only AD patients but also non-AD-type dementia patients. However, our finding is based on a relatively small number of patients and therefore should be replicated in a larger cohort. In addition, it will be necessary to categorize these participants by longitudinal follow-up and postmortem pathological examinations.

  8. Functional variability in butyrylcholinesterase activity regulates intrathecal cytokine and astroglial biomarker profiles in patients with Alzheimer's disease.

    PubMed

    Darreh-Shori, Taher; Vijayaraghavan, Swetha; Aeinehband, Shahin; Piehl, Fredrik; Lindblom, Rickard P F; Nilsson, Bo; Ekdahl, Kristina N; Långström, Bengt; Almkvist, Ove; Nordberg, Agneta

    2013-11-01

    Butyrylcholinesterase (BuChE) activity is associated with activated astrocytes in Alzheimer's disease brain. The BuChE-K variant exhibits 30%-60% reduced acetylcholine (ACh) hydrolyzing capacity. Considering the increasing evidence of an immune-regulatory role of ACh, we investigated if genetic heterogeneity in BuChE affects cerebrospinal fluid (CSF) biomarkers of inflammation and cholinoceptive glial function. Alzheimer's disease patients (n = 179) were BCHE-K-genotyped. Proteomic and enzymatic analyses were performed on CSF and/or plasma. BuChE genotype was linked with differential CSF levels of glial fibrillary acidic protein, S100B, interleukin-1β, and tumor necrosis factor (TNF)-α. BCHE-K noncarriers displayed 100%-150% higher glial fibrillary acidic protein and 64%-110% higher S100B than BCHE-K carriers, who, in contrast, had 40%-80% higher interleukin-1β and 21%-27% higher TNF-α compared with noncarriers. A high level of CSF BuChE enzymatic phenotype also significantly correlated with higher CSF levels of astroglial markers and several factors of the innate complement system, but lower levels of proinflammatory cytokines. These individuals also displayed beneficial paraclinical and clinical findings, such as high cerebral glucose utilization, low β-amyloid load, and less severe progression of clinical symptoms. In vitro analysis on human astrocytes confirmed the involvement of a regulated BuChE status in the astroglial responses to TNF-α and ACh. Histochemical analysis in a rat model of nerve injury-induced neuroinflammation, showed focal assembly of astroglial cells in proximity of BuChE-immunolabeled sites. In conclusion, these results suggest that BuChE enzymatic activity plays an important role in regulating intrinsic inflammation and activity of cholinoceptive glial cells and that this might be of clinical relevance. The dissociation between astroglial markers and inflammatory cytokines indicates that a proper activation and maintenance of

  9. Inflammation, immunity, and Alzheimer's disease.

    PubMed

    Town, Terrence

    2010-04-01

    Few topics in the field of Alzheimer's disease (AD) research have brought about the level of excitement and interest as the role of inflammation and immunity in the pathobiology and treatment of the disease. In this special issue of the journal, experts in the field give their views on how inflammatory processes and the immune system intersect- at both etiological and treatment levels- with disease biology. Collectively, nearly three decades of work are covered in this special issue, beginning with the first epidemiologic studies that showed an inverse risk relationship between AD and use of non-steroidal anti-inflammatory drugs, and ending with "immunotherapy" approaches and recent studies examining the roles of innate immune cells including microglia and peripheral mononuclear phagocytes in AD. Despite considerable work in this area, many important questions remain concerning the nature and timing of immune/inflammatory responses in the context of AD, and at what point and how to therapeutically intervene.

  10. [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.

  11. 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.

  12. [Study methods of drugs in Alzheimer disease].

    PubMed

    Dubois, B; Stehlé, B; Lehner, J P; Derouesné, C; Bourin, M; Lamour, Y; Blin, O; Jourdain, G; Alperovitch, A

    1996-01-01

    The availability of new drugs for Alzheimer's disease, with different pharmacological profiles, leads to a redefinition the relevant methodology for developing drugs in this indication, including the inclusion/exclusion criteria, the duration of the studies, and therefore, the relevant guidelines. This was the purpose of the Giens Round-table devoted to the new methodology for drug development in Alzheimer disease.

  13. Commentary on "a roadmap for the prevention of dementia II. Leon Thal Symposium 2008." Centers of excellence in Alzheimer's disease: it is time to better integrate patient care and clinical research to improve the prevention and treatment of Alzheimer's disease.

    PubMed

    Doody, Rachelle S

    2009-03-01

    Despite enormous worldwide public and private interest in improving the prevention and treatment of Alzheimer's disease (AD), we have not made as much of an impact as we would like, and the number of affected individuals continues to grow. Even more alarmingly, whereas global efforts to identify AD cases and to develop new treatments are increasing, patient-care options are disappearing, so that even if a highly efficacious therapy or prevention approach arose, it would not be used effectively. As a first step toward organizing a better way forward, we should establish AD centers of excellence that mandate both patient care and research in the same setting. These centers would benefit from changes in public health policies related to chronic-disease surveillance, Center for Medicare and Medicaid Services funding for the care of chronic diseases, institutional review boards, good clinical practice guidelines, National Institutes of Health regulations for the use of research funds, Food and Drug Administration guidelines for the approval of AD drugs, and Department of Commerce regulations related to patent protection of AD diagnostic aids and treatments. This new form of AD centers of excellence would also provide direct care to many patients and their families, model care for communities and medical trainees, enhance the voluntary recruitment of AD patients to clinical trials, and improve our understanding of AD and its management.

  14. A protective mutation against Alzheimer disease?

    PubMed

    Proft, Juliane; Weiss, Norbert

    2012-07-01

    To date, nearly 35.6 million people world wide live with dementia, and the situation is going to get worse by 2050 with 115.4 million cases.(1) In the western world, the prevalence for dementia in people over the age of 60 is greater than 5% and two thirds are due to Alzheimer disease,(2) (-) (5) the most common form of dementias.   Alzheimer disease (AD), first described as "presenile dementia" by the German psychiatrist and neuropathologist Alois Alzheimer in 1906,(6) is a devastating disease characterized by progressive cognitive deterioration, as well as impairments in behavior, language, and visuospatial skills.(7) Furthermore, Alzheimer discovered the presence of intraneuronal tangles and extracellular amyloid plaques in the diseased-damaged brain, the hallmarks of Alzheimer disease.

  15. Alzheimer's disease: molecular concepts and therapeutic targets

    NASA Astrophysics Data System (ADS)

    Fassbender, K.; Masters, C.; Beyreuther, K.

    2001-06-01

    The beta amyloid peptide is the major component of the neuritic plaques, the characteristic lesions in Alzheimer's disease. Mutations in three genes (APP, PS-1, and PS-2) cause familial Alzheimer's disease by alteration of the rate of generation of amyloid peptide or the length of this peptide. However, in the 90% non-familial cases, other factors play a major pathogenetic role. These include the apolipoprotein E genotype, the "plaque-associated" proteins promoting the formation of toxic fibrillar aggregates or the chronic inflammatory responses. The aim of this review is to explain the steps in the complex cascade leading to Alzheimer's disease and, based on this, to report the current efforts to intervene in these different pathophysiological events in order to prevent progression of Alzheimer's disease. Whereas acetylcholine substitution is currently used in clinical practice, future therapeutical strategies to combat Alzheimer's disease may include anti-inflammatory treatments, vaccination against beta amyloid peptide, or treatment with cholesterol-lowering drugs.

  16. 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. PMID:27372640

  17. 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.

  18. Changes of several brain receptor complexes in the cerebral cortex of patients with Alzheimer disease: probable new potential pharmaceutical targets.

    PubMed

    Falsafi, Soheil Keihan; Roßner, Steffen; Ghafari, Maryam; Groessl, Michael; Morawski, Markus; Gerner, Christopher; Lubec, Gert

    2014-01-01

    Although Alzheimer disease (AD) has been linked to defects in major brain receptors, studies thus far have been limited to the determination of receptor subunits or specific ligand binding studies. However, the availability of current technology enables the determination and quantification of brain receptor complexes. Thus, we examined levels of native receptor complexes in the brains of patients with AD. Cortical tissue was obtained from control subjects (n = 12 females and 12 males) and patients with AD (n = 12 females and 12 males) within a 3-h postmortem time period. The tissues were kept frozen until further biochemical analyses. Membrane proteins were extracted and subsequently enriched by ultracentrifugation using a sucrose gradient. Membrane proteins were then electrophoresed onto native gels and immunoblotted using antibodies against individual brain receptors. We found that the levels were comparable for complexes containing GluR2, GluR3 and GluR4 as well as 5-HT1A. Moreover, the levels of complexes containing muscarinic AChR M1, NR1 and GluR1 were significantly increased in male patients with AD. Nicotinic AChRs 4 and 7 as well as dopaminergic receptors D1 and D2 were also increased in males and females with AD. These findings reveal a pattern of altered receptor complex levels that may contribute to the deterioration of the concerted activity of these receptors and thus result in cognitive deficits observed in patients with AD. It should be emphasised that receptor complexes function as working units rather than individual subunits. Thus, the receptor deficits identified may be relevant for the design of experimental therapies. Therefore, specific pharmacological modulation of these receptors is within the pharmaceutical repertoire.

  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. 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. PMID:25547862

  1. 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.

  2. 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. PMID:26338814

  3. Alzheimer's Disease | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Alzheimer's Disease Alzheimer's Treatment Past Issues / Winter 2015 Table of Contents Currently, there is no cure for Alzheimer's. Because it is a complex disease, scientists believe ...

  4. [Vaccination therapy for Alzheimer's disease].

    PubMed

    Tabira, Takeshi

    2009-11-01

    Since AN-1792 vaccine induced autoimmune encephalitis, several pharmaceutical companies are now concentrated in developing antibody therapy in Alzheimer's disease (AD). Each antibody has own characteristics. Thus, it is unpredictable at present which antibody is the most beneficial until we see the result of clinical trials. If disease modifying antibodies were found, they will be widely used for treatment of AD in near future. As a candidate of such antibodies, we have developed TAPIR-like antibody with much higher affinity to Abeta42 than Abeta40, and it effectively deleted senile plaque amyloid and Abeta oligomers without increasing microhemorrhages. Although passive immunization can avoid autoimmune encephalitis, it is expensive and it is not suitable for prevention. Thus, safe vaccines by active immunization would be better. Vaccines that induce Th2 type immune responses such as oral vaccine or per-nasal vaccine would be promising. PMID:20030228

  5. MRI morphometry in Alzheimer's disease.

    PubMed

    Matsuda, Hiroshi

    2016-09-01

    MRI based evaluation of brain atrophy is regarded as a valid method to stage the disease and to assess progression in Alzheimer's disease (AD). Volumetric software programs have made it possible to quantify gray matter in the human brain in an automated fashion. At present, voxel based morphometry (VBM) is easily applicable to the routine clinical procedure with a short execution time. The importance of the VBM approach is that it is not biased to one particular structure and is able to assess anatomical differences throughout the brain. Stand-alone VBM software running on Windows, Voxel-based Specific Regional analysis system for AD (VSRAD), has been widely used in the clinical diagnosis of AD in Japan. On the other hand, recent application of graph theory to MRI has made it possible to analyze changes in structural connectivity in AD.

  6. Nicotinic receptors and Alzheimer's disease.

    PubMed

    Bourin, Michel; Ripoll, Nadège; Dailly, Eric

    2003-01-01

    Nicotinic receptors (NRs) belong to the group of polymeric receptors of the cell membrane and are key elements of cholinergic transmission. Numerous subtypes of NRs exist with the alpha 4 beta 2 and alpha 7 types being encountered most frequently. Deficiencies in NRs seem to play a role in Alzheimer's disease, which is characterised by accumulation of senile plaques, mainly composed of beta-amyloid peptide (beta A). Although the aetiology of this disease is unknown, different pathogenesis hypotheses implicating alpha 7 NRs have been proposed, with the receptors exerting a direct or indirect action on the mechanism of beta A toxicity. Allosteric modulators of NRs, such as the cholinesterase inhibitor galantamine, that facilitate the action of acetylcholine on these receptors may provide therapeutic benefits in the areas of cognition, attention and antineurodegenerative activity.

  7. Older adults with Alzheimer's disease in a faith community.

    PubMed

    Tompkins, Catherine j; Sorrell, Jeanne M

    2008-01-01

    In the first phase of this study, focus groups were conducted with 12 clergy to explore how to meet the needs of Alzheimer's disease patients and their families. The clergy reported that although they do reach out to these families, they have not received formal training, so they often do not know what families need. Members of their congregations who are trained in working with Alzheimer's patients need to partner with the clergy in reaching out to these families. Although this article mainly focuses on the clergy's perspective, in the second phase of the study, caregivers and early-stage Alzheimer's patients were asked to describe their experiences of spiritual connections related to Alzheimer's disease.

  8. Alzheimer's Disease - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Bosnian (Bosanski) Chinese - Simplified (简体中文) Chinese - Traditional (繁體中文) French (français) German (Deutsch) Hindi (हिन्दी) Italian (italiano) ... English 探索大腦之旅: 點圖解密 - 繁體中文 (Chinese - Traditional) Alzheimer's Association French (français) Alzheimer's Disease Maladie d'Alzheimer - français (French) ...

  9. Brain histamine in Alzheimer's disease.

    PubMed

    Cacabelos, R; Yamatodani, A; Niigawa, H; Hariguchi, S; Tada, K; Nishimura, T; Wada, H; Brandeis, L; Pearson, J

    1989-05-01

    The concentration of histamine (HA) has been determined by high-performance liquid chromatography (HPLC) with fluorometric detection in 21 different regions of brains from patients with senile dementia of the Alzheimer type (SDAT) and subjects (CB) whose causes of death were not related to neuropsychiatric, neurological and/or neurodegenerative diseases. The highest levels of HA in the central nervous system (CNS) of both control (CB) and SDAT samples were found in the posterior hypothalamus (CB = 3.13 +/- 0.63 pmol/mg; SDAT = 7.75 +/- 1.43 pmol/mg, p less than 0.005), where the HA neurons are located, and in the anterior hypothalamus (CB = 1.77 +/- 0.33 pmol/mg; SDAT = 2.82 +/- 0.45 pmol/mg, p less than 0.005). The lowest HA levels were detected in the cerebellum (CB = 0.12 +/- 0.04 pmol/mg; SDAT = 0.24 +/- 0.09 pmol/mg, p less than 0.01) and medulla oblongata. HA levels were significantly higher in SDAT than in CB in the following areas: motor cortex (Brodmann's area 4) (A4), premotor cortex (A6), postcentral gyrus (A1,2), posterior parietal cortex (A5,7), superior temporal gyrus (A41,42), temporal pole (A38), primary and secondary visual cortices (A17,18), anterior and posterior regions of the hypothalamus, putamen, caudate nucleus, nucleus accumbens, thalamus, hippocampus, pons, medulla oblongata and cerebellum. No changes were seen in globus pallidus and corpus callosum. Since the origin of HA in the brain is dependent upon three main compartments (neuronal, mast cell, vascular smooth muscle), with approximately 60-80% of the total HA belonging to the neuronal pool, on the basis of neurochemical data we postulate that the increase in the levels of HA in SDAT might account for or be associated with alterations in neuroendocrine, cognitive, neurovascular and sleep-wakefulness functions. PMID:2755282

  10. Pre-critical MRI findings of an Alzheimer's disease patient with pathologically proven cerebral amyloid angiopathy related lobar hemorrhage.

    PubMed

    Nonaka, Toshihiro; Yakushiji, Yusuke; Ide, Toshihiro; Ito, Hiroshi; Kawamoto, Kazuhiro; Hara, Hideo

    2016-05-31

    An 85-year-old woman with untreated hypertension was admitted with a disturbance of consciousness. On admission, brain CT revealed a lobar intracerebral hemorrhage with a midline shift. An intracranial hematoma was evacuated via a life-saving craniotomy. Definite pathological findings of amyloid-β deposition in the excised hematoma (strong in anti-amyloid β40 immunostain, but weak in anti- amyloid β42) indicated cerebral amyloid angiopathy (CAA). She had been diagnosed with Alzheimer's disease at a regional memory clinic one month before symptom onset based on MRI findings of medial temporal lobe atrophy as well as CAA-related features of multiple strictly lobar cerebral microbleeds in the occipital lobe, cortical superficial siderosis and >20 enlarged perivascular spaces in the centrum semiovale. This experience suggests that comprehensive interpretation of such CAA-related findings on MRI might help to improve the management of cardiovascular risk factors for Alzheimer's disease. PMID:27151228

  11. Antigonadotropins: a novel strategy to halt Alzheimer's disease progression.

    PubMed

    Gregory, Christopher W; Atwood, Craig S; Smith, Mark A; Bowen, Richard L

    2006-01-01

    A significant amount of research has been focused on the relationship between hormones and Alzheimer's disease. However, the majority of this work has been on estrogen and more recently testosterone. A serendipitous patient encounter led one of us (RLB) to question whether other hormones of the hypothalamic-pituitary-gonadal axis could be playing a role in the pathogenesis of Alzheimer's disease. The age-related decline in reproductive function results in a dramatic decrease in serum estrogen and testosterone concentrations and an equally dramatic compensatory increase in serum luteinizing hormone concentrations. Indeed, there is growing evidence that the gonadotropin, luteinizing hormone, which regulates serum estrogen and testosterone concentrations, could be an important causative factor in the development of Alzheimer's disease. This review provides information supporting the "gonadotropin hypothesis," puts forth a novel mechanism of how changes in serum luteinizing hormone concentrations could contribute to the pathogenesis of Alzheimer's disease, and discusses potential therapeutic anti-gonadotropin compounds.

  12. 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 2010 Table of Contents The ... Suncoast Gerontology Center, University of South Florida. How Alzheimer's Changes the Brain The only definite way to ...

  13. 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.

  14. 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.

  15. 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

  16. Mitochondrial Drugs for Alzheimer Disease.

    PubMed

    Bonda, David J; Wang, Xinglong; Gustaw-Rothenberg, Katarzyna A; Perry, George; Smith, Mark A; Zhu, Xiongwei

    2009-12-23

    Therapeutic strategies for Alzheimer disease (AD) have yet to offer a disease-modifying effect to stop the debilitating progression of neurodegeneration and cognitive decline. Rather, treatments thus far are limited to agents that slow disease progression without halting it, and although much work towards a cure is underway, a greater understanding of disease etiology is certainly necessary for any such achievement. Mitochondria, as the centers of cellular metabolic activity and the primary generators of reactive oxidative species in the cell, received particular attention especially given that mitochondrial defects are known to contribute to cellular damage. Furthermore, as oxidative stress has come to the forefront of AD as a causal theory, and as mitochondrial damage is known to precede much of the hallmark pathologies of AD, it seems increasingly apparent that this metabolic organelle is ultimately responsible for much, if not all of disease pathogenesis. In this review, we review the role of neuronal mitochondria in the pathogenesis of AD and critically assess treatment strategies that utilize this upstream access point as a method for disease prevention. We suspect that, with a revived focus on mitochondrial repair and protection, an effective and realistic therapeutic agent can be successfully developed. PMID:20657666

  17. Mitochondrial Drugs for Alzheimer Disease

    PubMed Central

    Bonda, David J.; Wang, Xinglong; Gustaw-Rothenberg, Katarzyna A.; Perry, George; Smith, Mark A.; Zhu, Xiongwei

    2009-01-01

    Therapeutic strategies for Alzheimer disease (AD) have yet to offer a disease-modifying effect to stop the debilitating progression of neurodegeneration and cognitive decline. Rather, treatments thus far are limited to agents that slow disease progression without halting it, and although much work towards a cure is underway, a greater understanding of disease etiology is certainly necessary for any such achievement. Mitochondria, as the centers of cellular metabolic activity and the primary generators of reactive oxidative species in the cell, received particular attention especially given that mitochondrial defects are known to contribute to cellular damage. Furthermore, as oxidative stress has come to the forefront of AD as a causal theory, and as mitochondrial damage is known to precede much of the hallmark pathologies of AD, it seems increasingly apparent that this metabolic organelle is ultimately responsible for much, if not all of disease pathogenesis. In this review, we review the role of neuronal mitochondria in the pathogenesis of AD and critically assess treatment strategies that utilize this upstream access point as a method for disease prevention. We suspect that, with a revived focus on mitochondrial repair and protection, an effective and realistic therapeutic agent can be successfully developed. PMID:20657666

  18. 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.

  19. 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. PMID:16042022

  20. Living with an Alzheimer patient in Turkey.

    PubMed

    Taşc, Sultan; Tekinsoy Kartn, Pnar; Ceyhan, Ozlem; Sungur, Gönül; Göriş, Songül

    2012-08-01

    The research was performed to determine the problems that caregivers experience with patients with Alzheimer disease. The research was carried out qualitatively with those who were responsible for the care of eight Alzheimer patients who were being treated at the Neurology Polyclinics of Gevher Nesibe Hospital at Erciyes University in Kayseri, Turkey. Research data were collected through questionnaires designed to understand the characteristics of the individuals who provided care and focus group interviews. A written consent from the institution and an oral as well as written consent of the individuals were obtained. Focus groups were interviewed in the same setting at different times with two different groups, including four people who agreed to participate in the research. Each interview was conducted by three personnel: a moderator, a reporter, and an observer. Interviews were structured under four main titles: "The changes seen in the individual with Alzheimer disease"; "Physical, social, psychological, and socioeconomical problems that caregivers experienced"; "Precautions taken against the problems"; and "Patients' expectations of the care". The interviews lasted for approximately 2 hours. A voice recorder and a written registration form were also used to collect information. Six women and two men constituted the research group. The caregivers stated that the patients had such difficulties as forgetfulness, nervousness, jealousy, childish behavior, deterioration in speech, fear of water, hallucinations, and difficulty in carrying out daily life activities. Caregivers emphasized the fact that they perceived the changes in the patients as deliberate behaviors and thus became annoyed and quarreled with them before diagnosis; however, after diagnosis, they felt remorse and experienced guilt because of their ill-treatment of them. In addition, the caregivers hid the patients and their disease from social surroundings. Caregivers mentioned that they had felt as

  1. Living with an Alzheimer patient in Turkey.

    PubMed

    Taşc, Sultan; Tekinsoy Kartn, Pnar; Ceyhan, Ozlem; Sungur, Gönül; Göriş, Songül

    2012-08-01

    The research was performed to determine the problems that caregivers experience with patients with Alzheimer disease. The research was carried out qualitatively with those who were responsible for the care of eight Alzheimer patients who were being treated at the Neurology Polyclinics of Gevher Nesibe Hospital at Erciyes University in Kayseri, Turkey. Research data were collected through questionnaires designed to understand the characteristics of the individuals who provided care and focus group interviews. A written consent from the institution and an oral as well as written consent of the individuals were obtained. Focus groups were interviewed in the same setting at different times with two different groups, including four people who agreed to participate in the research. Each interview was conducted by three personnel: a moderator, a reporter, and an observer. Interviews were structured under four main titles: "The changes seen in the individual with Alzheimer disease"; "Physical, social, psychological, and socioeconomical problems that caregivers experienced"; "Precautions taken against the problems"; and "Patients' expectations of the care". The interviews lasted for approximately 2 hours. A voice recorder and a written registration form were also used to collect information. Six women and two men constituted the research group. The caregivers stated that the patients had such difficulties as forgetfulness, nervousness, jealousy, childish behavior, deterioration in speech, fear of water, hallucinations, and difficulty in carrying out daily life activities. Caregivers emphasized the fact that they perceived the changes in the patients as deliberate behaviors and thus became annoyed and quarreled with them before diagnosis; however, after diagnosis, they felt remorse and experienced guilt because of their ill-treatment of them. In addition, the caregivers hid the patients and their disease from social surroundings. Caregivers mentioned that they had felt as

  2. [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. PMID:26395306

  3. 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.

  4. 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. PMID:24412285

  5. Alzheimer's disease & metals: therapeutic opportunities

    PubMed Central

    Kenche, Vijaya B; Barnham, Kevin J

    2011-01-01

    Alzheimer's disease (AD) is the most common age related neurodegenerative disease. Currently, there are no disease modifying drugs, existing therapies only offer short-term symptomatic relief. Two of the pathognomonic indicators of AD are the presence of extracellular protein aggregates consisting primarily of the Aβ peptide and oxidative stress. Both of these phenomena can potentially be explained by the interactions of Aβ with metal ions. In addition, metal ions play a pivotal role in synaptic function and their homeostasis is tightly regulated. A breakdown in this metal homeostasis and the generation of toxic Aβ oligomers are likely to be responsible for the synaptic dysfunction associated with AD. Therefore, approaches that are designed to prevent Aβ metal interactions, inhibiting the formation of toxic Aβ species as well as restoring metal homeostasis may have potential as disease modifying strategies for treating AD. This review summarizes the physiological and pathological interactions that metal ions play in synaptic function with particular emphasis placed on interactions with Aβ. A variety of therapeutic strategies designed to address these pathological processes are also described. The most advanced of these strategies is the so-called ‘metal protein attenuating compound’ approach, with the lead molecule PBT2 having successfully completed early phase clinical trials. The success of these various strategies suggests that manipulating metal ion interactions offers multiple opportunities to develop disease modifying therapies for AD. PMID:21232050

  6. 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.

  7. 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.

  8. Alzheimer's disease in one monozygotic twin

    PubMed Central

    Hunter, Richard; Dayan, A. D.; Wilson, John

    1972-01-01

    A woman of 64 died after an illness lasting 15 years and characterized by a progressive amnesic syndrome followed by global dementia. The brain showed changes typical of Alzheimer's disease. Her monozygotic twin sister was clinically not affected and died two years later of carcinoma. This is the second report of monozygotic twin sisters apparently discordant for presenile dementia of Alzheimer type. PMID:5084139

  9. Biomarker Modeling of Alzheimer's Disease

    PubMed Central

    Jack, Clifford R; Holtzman, David M

    2014-01-01

    Alzheimer's disease (AD) is a slowly progressing disorder in which pathophysiological abnormalities, detectable in vivo by biomarkers, precede overt clinical symptoms by many years to decades. Five AD biomarkers are sufficiently validated to have been incorporated into clinical diagnostic criteria and commonly used in therapeutic trials. Current AD biomarkers fall into 2 categories: biomarkers of amyloid-β plaques and of tau-related neurodegeneration. Three of the 5 are imaging measures and two are cerebrospinal fluid analytes. AD biomarkers do not evolve in an identical manner but rather in a sequential but temporally overlapping manner. Models of the temporal evolution of AD biomarkers can take the form of plots of biomarker severity (degree of abnormality) vs. time. In this review we discuss several time-dependent models of AD which take into consideration varying age of onset (early vs. late) and the influence of aging and co-occurring brain pathologies that commonly arise in the elderly. PMID:24360540

  10. The Genetics of Alzheimer Disease

    PubMed Central

    Tanzi, Rudolph E.

    2012-01-01

    Family history is the second strongest risk factor for Alzheimer disease (AD) following advanced age. Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations in APP, PSEN1, and PSEN2 virtually guarantee early-onset (<60 years) familial AD, which represents ∼5% of AD. On the other hand, common gene polymorphisms, such as the ε4 and ε2 variants of the APOE gene, can influence susceptibility for ∼50% of the common late-onset AD. These four genes account for 30%–50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of 11 additional AD candidate genes. This paper reviews the past, present, and future attempts to elucidate the complex and heterogeneous genetic underpinnings of AD. PMID:23028126

  11. [Alzheimer's disease: the infectious hypothesis].

    PubMed

    Roubaud Baudron, Claire; Varon, Christine; Mégraud, Francis; Salles, Nathalie

    2015-12-01

    Several hypotheses are proposed for understanding the Alzheimer's disease (AD) pathological mechanisms, mainly the amyloid theory, but the process inducing Aß peptide deposit, tau protein degeneration, and ultimately neuronal loss, is still to be elucidated. Alteration of the blood-brain barrier and activation of neuroinflammation seem to play an important role in AD neurodegeneration, especially in the decrease of Aß peptide clearance, therefore suggesting a role of infectious agents. Epidemiological and experimental studies on cellular or murine models related to herpes simplex virus (HSV), spirochetes, Chlamydia pneumoniae or Borrelia, and systemic inflammation are reviewed. Aß peptide or tau protein could also behave like a prion protein. Infectious agents could thus have an impact on AD by direct interaction with neurotropism or systemic inflammation. Although the results of these studies are not conclusive, they may contribute to the understanding of AD pathology. PMID:26707559

  12. Structural networks in Alzheimer's disease.

    PubMed

    Reid, Andrew T; Evans, Alan C

    2013-01-01

    Alzheimer's disease (AD) appears to be a uniquely human condition, which is possibly attributable to our expanded longevity and peculiar capacity for episodic memory. Due to a lack of naturally-occurring animal model for investigating AD pathogenesis, our knowledge about the disease must be derived from correlational observation of humans, or from animal models produced by genetic manipulation of known risk factors in humans. Advances in neuroimaging, cellular and molecular science, and computational methods have proven useful for the improvement of such techniques, but the general limitation persists; as a result we remain without clear answers to some of the fundamental questions posed by AD. On the other hand, much progress has been made in characterizing the longitudinal progression of AD pathology, which includes the formation of "plaques and tangles", a distinct topological pattern of atrophy of grey and white matter, and the concurrent decline of specific cognitive functions, beginning with mild memory impairments and ending with general debilitating dementia. In this review, we first discuss the existing literature which characterizes AD etiology, pathology, and pathogenesis, with the intention of framing the disease as primarily a "disconnection syndrome". We next describe methodologies for investigating the topological properties of human brain networks, using graph theoretical techniques and connectivity information derived from anatomical and diffusion-weighted MR imaging. Finally, we discuss how these methodologies have been applied to systems-level analyses of AD, to help characterize the network changes underlying the disease process, and how these patterns relate to specific cognitive outcome measures. PMID:23294972

  13. 77 FR 11116 - Draft National Plan To Address Alzheimer's Disease

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-24

    ... HUMAN SERVICES Draft National Plan To Address Alzheimer's Disease AGENCY: Office of the Assistant.... SUMMARY: HHS is soliciting public input on the draft National Plan to Address Alzheimer's Disease, which... Alzheimer's disease. Coordinate Alzheimer's disease research and services across all federal...

  14. 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…

  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. 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

  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. Neuronal histamine and cognitive symptoms in Alzheimer's disease.

    PubMed

    Zlomuzica, Armin; Dere, Dorothea; Binder, Sonja; De Souza Silva, Maria Angelica; Huston, Joseph P; Dere, Ekrem

    2016-07-01

    Alzheimer's disease is a neurodegenerative disorder characterized by extracellular amyloid plaque deposits, mainly composed of amyloid-beta peptide and intracellular neurofibrillary tangles consisting of aggregated hyperphosphorylated tau protein. Amyloid-beta represents a neurotoxic proteolytic cleavage product of amyloid precursor protein. The progressive cognitive decline that is associated with Alzheimer's disease has been mainly attributed to a deficit in cholinergic neurotransmission due to the continuous degeneration of cholinergic neurons e.g. in the basal forebrain. There is evidence suggesting that other neurotransmitter systems including neuronal histamine also contribute to the development and maintenance of Alzheimer's disease-related cognitive deficits. Pathological changes in the neuronal histaminergic system of such patients are highly predictive of ensuing cognitive deficits. Furthermore, histamine-related drugs, including histamine 3 receptor antagonists, have been demonstrated to alleviate cognitive symptoms in Alzheimer's disease. This review summarizes findings from animal and clinical research on the relationship between the neuronal histaminergic system and cognitive deterioration in Alzheimer's disease. The significance of the neuronal histaminergic system as a promising target for the development of more effective drugs for the treatment of cognitive symptoms is discussed. Furthermore, the option to use histamine-related agents as neurogenesis-stimulating therapy that counteracts progressive brain atrophy in Alzheimer's disease is considered. This article is part of a Special Issue entitled 'Histamine Receptors'.

  19. Alois Alzheimer and Alzheimer's disease: a centennial perspective.

    PubMed

    Small, David H; Cappai, Roberto

    2006-11-01

    The year 2006 is the centenary of the famous presentation of Alois Alzheimer which first described the neuropathology of Alzheimer's disease (AD). Since this presentation, enormous progress has been made in understanding the biology of AD. The central role of the beta-amyloid protein (Abeta) in the pathogenesis of AD and the relationship between plaque and tangle pathology is now much better understood. In this article, we review the current status of the amyloid hypothesis of AD and its role in the development of future therapy.

  20. 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

  1. Can Infections Cause Alzheimer's Disease?

    PubMed Central

    Mawanda, Francis; Wallace, Robert

    2013-01-01

    Late-onset Alzheimer's disease (AD) is the most prevalent cause of dementia among older adults, yet more than a century of research has not determined why this disease develops. One prevailing hypothesis is that late-onset AD is caused by infectious pathogens, an idea widely studied in both humans and experimental animal models. This review examines the infectious AD etiology hypothesis and summarizes existing evidence associating infectious agents with AD in humans. The various mechanisms through which different clinical and subclinical infections could cause or promote the progression of AD are considered, as is the concordance between putative infectious agents and the epidemiology of AD. We searched the PubMed, Web of Science, and EBSCO databases for research articles pertaining to infections and AD and systematically reviewed the evidence linking specific infectious pathogens to AD. The evidence compiled from the literature linking AD to an infectious cause is inconclusive, but the amount of evidence suggestive of an association is too substantial to ignore. Epidemiologic, clinical, and basic science studies that could improve on current understanding of the associations between AD and infections and possibly uncover ways to control this highly prevalent and debilitating disease are suggested. PMID:23349428

  2. Alzheimer's disease: The role for neurosurgery

    PubMed Central

    Pereira, Julio Leonardo Barbosa; Downes, Angela; Gorgulho, Alessandra; Patel, Vishal; Malkasian, Dennis; De Salles, Antonio

    2014-01-01

    Dementia, most commonly caused by Alzheimer's disease (AD), affects approximately 35 million people worldwide, with the incidence expected to increase as the population ages. After decades of investigation, AD is now understood to be a complex disease that affects behavior and cognition through several mechanisms: Disrupted neuronal communication, abnormal regional tissue metabolism, and impaired cellular repair. Existing therapies have demonstrated limited efficacy, which has spurred the search for specific disease markers and predictors as well as innovative therapeutic options. Deep brain stimulation (DBS) of the memory circuits is one such option, with early studies suggesting that modulation of neural activity in these networks may improve cognitive function. Encapsulated cell biodelivery (ECB) is a device that delivers nerve growth factor to the cholinergic basal forebrain to potentially improve cognitive decline in AD patients. This review discusses the pathogenesis of AD, novel neuroimaging and biochemical markers, and the emerging role for neurosurgical applications such as DBS and ECB. PMID:25289167

  3. Alzheimer's disease: The role for neurosurgery.

    PubMed

    Pereira, Julio Leonardo Barbosa; Downes, Angela; Gorgulho, Alessandra; Patel, Vishal; Malkasian, Dennis; De Salles, Antonio

    2014-01-01

    Dementia, most commonly caused by Alzheimer's disease (AD), affects approximately 35 million people worldwide, with the incidence expected to increase as the population ages. After decades of investigation, AD is now understood to be a complex disease that affects behavior and cognition through several mechanisms: Disrupted neuronal communication, abnormal regional tissue metabolism, and impaired cellular repair. Existing therapies have demonstrated limited efficacy, which has spurred the search for specific disease markers and predictors as well as innovative therapeutic options. Deep brain stimulation (DBS) of the memory circuits is one such option, with early studies suggesting that modulation of neural activity in these networks may improve cognitive function. Encapsulated cell biodelivery (ECB) is a device that delivers nerve growth factor to the cholinergic basal forebrain to potentially improve cognitive decline in AD patients. This review discusses the pathogenesis of AD, novel neuroimaging and biochemical markers, and the emerging role for neurosurgical applications such as DBS and ECB.

  4. A rare duplication on chromosome 16p11.2 is identified in patients with psychosis in Alzheimer's disease.

    PubMed

    Zheng, Xiaojing; Demirci, F Yesim; Barmada, M Michael; Richardson, Gale A; Lopez, Oscar L; Sweet, Robert A; Kamboh, M Ilyas; Feingold, Eleanor

    2014-01-01

    Epidemiological and genetic studies suggest that schizophrenia and autism may share genetic links. Besides common single nucleotide polymorphisms, recent data suggest that some rare copy number variants (CNVs) are risk factors for both disorders. Because we have previously found that schizophrenia and psychosis in Alzheimer's disease (AD+P) share some genetic risk, we investigated whether CNVs reported in schizophrenia and autism are also linked to AD+P. We searched for CNVs associated with AD+P in 7 recurrent CNV regions that have been previously identified across autism and schizophrenia, using the Illumina HumanOmni1-Quad BeadChip. A chromosome 16p11.2 duplication CNV (chr16: 29,554,843-30,105,652) was identified in 2 of 440 AD+P subjects, but not in 136 AD subjects without psychosis, or in 593 AD subjects with intermediate psychosis status, or in 855 non-AD individuals. The frequency of this duplication CNV in AD+P (0.46%) was similar to that reported previously in schizophrenia (0.46%). This duplication CNV was further validated using the NanoString nCounter CNV Custom CodeSets. The 16p11.2 duplication has been associated with developmental delay, intellectual disability, behavioral problems, autism, schizophrenia (SCZ), and bipolar disorder. These two AD+P patients had no personal of, nor any identified family history of, SCZ, bipolar disorder and autism. To the best of our knowledge, our case report is the first suggestion that 16p11.2 duplication is also linked to AD+P. Although rare, this CNV may have an important role in the development of psychosis. PMID:25379732

  5. A biophysical model of brain deformation to simulate and analyze longitudinal MRIs of patients with Alzheimer's disease.

    PubMed

    Khanal, Bishesh; Lorenzi, Marco; Ayache, Nicholas; Pennec, Xavier

    2016-07-01

    We propose a framework for developing a comprehensive biophysical model that could predict and simulate realistic longitudinal MRIs of patients with Alzheimer's disease (AD). The framework includes three major building blocks: i) atrophy generation, ii) brain deformation, and iii) realistic MRI generation. Within this framework, this paper focuses on a detailed implementation of the brain deformation block with a carefully designed biomechanics-based tissue loss model. For a given baseline brain MRI, the model yields a deformation field imposing the desired atrophy at each voxel of the brain parenchyma while allowing the CSF to expand as required to globally compensate for the locally prescribed volume loss. Our approach is inspired by biomechanical principles and involves a system of equations similar to Stokes equations in fluid mechanics but with the presence of a non-zero mass source term. We use this model to simulate longitudinal MRIs by prescribing complex patterns of atrophy. We present experiments that provide an insight into the role of different biomechanical parameters in the model. The model allows simulating images with exactly the same tissue atrophy but with different underlying deformation fields in the image. We explore the influence of different spatial distributions of atrophy on the image appearance and on the measurements of atrophy reported by various global and local atrophy estimation algorithms. We also present a pipeline that allows evaluating atrophy estimation algorithms by simulating longitudinal MRIs from large number of real subject MRIs with complex subject-specific atrophy patterns. The proposed framework could help understand the implications of different model assumptions, regularization choices, and spatial priors for the detection and measurement of brain atrophy from longitudinal brain MRIs.

  6. 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…

  7. 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.

  8. Metaphor comprehension in Alzheimer's disease: novelty matters.

    PubMed

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

    2008-10-01

    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 non-conventional (novel) metaphor comprehension. This ability was not related to global cognitive deterioration or to deficits in the cognitive domains of attention, memory and language comprehension. On the other hand, the impairment in verbal reasoning appeared to be relevant for both novel and conventional metaphor comprehension. The relationship between novel metaphor comprehension and performance in the visual-spatial planning task of the Behavioral Assessment of the Dysexecutive Syndrome (BADS) suggests that executive impairment, possibly related to prefrontal dysfunction, may be responsible for the pAD patients' poor performance in novel metaphor comprehension. The present findings suggest a role of the prefrontal cortex in novel metaphor comprehension.

  9. Implicit memory for music in Alzheimer's disease.

    PubMed

    Halpern, A R; O'Connor, M G

    2000-07-01

    Short, unfamiliar melodies were presented to young and older adults and to Alzheimer's disease (AD) patients in an implicit and an explicit memory task. The explicit task was yes-no recognition, and the implicit task was pleasantness ratings, in which memory was shown by higher ratings for old versus new melodies (the mere exposure effect). Young adults showed retention of the melodies in both tasks. Older adults showed little explicit memory but did show the mere exposure effect. The AD patients showed neither. The authors considered and rejected several artifactual reasons for this null effect in the context of the many studies that have shown implicit memory among AD patients. As the previous studies have almost always used the visual modality for presentation, they speculate that auditory presentation, especially of nonverbal material, may be compromised in AD because of neural degeneration in auditory areas in the temporal lobes.

  10. 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.

  11. Dementia (Including Alzheimer Disease) (Beyond the Basics)

    MedlinePlus

    ... problems are caused by early Alzheimer disease. Normal age-related changes usually cause minor difficulties in short term memory and a slowed ability to learn and process information. These changes are usually mild and do not ...

  12. 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. PMID:26963387

  13. 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.

  14. 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;…

  15. Delaying the onset of Alzheimer disease

    PubMed Central

    Craik, Fergus I.M.; Bialystok, Ellen; Freedman, Morris

    2010-01-01

    Objectives: There is strong epidemiologic evidence to suggest that older adults who maintain an active lifestyle in terms of social, mental, and physical engagement are protected to some degree against the onset of dementia. Such factors are said to contribute to cognitive reserve, which acts to compensate for the accumulation of amyloid and other brain pathologies. We present evidence that lifelong bilingualism is a further factor contributing to cognitive reserve. Methods: Data were collected from 211 consecutive patients diagnosed with probable Alzheimer disease (AD). Patients' age at onset of cognitive impairment was recorded, as was information on occupational history, education, and language history, including fluency in English and any other languages. Following this procedure, 102 patients were classified as bilingual and 109 as monolingual. Results: We found that the bilingual patients had been diagnosed 4.3 years later and had reported the onset of symptoms 5.1 years later than the monolingual patients. The groups were equivalent on measures of cognitive and occupational level, there was no apparent effect of immigration status, and the monolingual patients had received more formal education. There were no gender differences. Conclusions: The present data confirm results from an earlier study, and thus we conclude that lifelong bilingualism confers protection against the onset of AD. The effect does not appear to be attributable to such possible confounding factors as education, occupational status, or immigration. Bilingualism thus appears to contribute to cognitive reserve, which acts to compensate for the effects of accumulated neuropathology. GLOSSARY AD = Alzheimer disease; MMSE = Mini-Mental State Examination. PMID:21060095

  16. Epigenetic Alterations in Alzheimer's Disease.

    PubMed

    Sanchez-Mut, Jose V; Gräff, Johannes

    2015-01-01

    Alzheimer's disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD. PMID:26734709

  17. Regenerative medicine in Alzheimer's disease.

    PubMed

    Felsenstein, Kevin M; Candelario, Kate M; Steindler, Dennis A; Borchelt, David R

    2014-04-01

    Identifying novel, effective therapeutics for Alzheimer's disease (AD) is one of the major unmet medical needs for the coming decade. Because the current paradigm for developing and testing disease-modifying AD therapies is protracted and likely to be even longer, with the shift toward earlier intervention in preclinical AD, it is an open issue whether we can develop, test, and widely deploy a novel therapy in time to help the current at-risk generation if we continue to follow the standard paradigms of discovery and drug development. There is an imperative need to find safe and effective preventive measures that can be distributed rapidly to stem the coming wave of AD that will potentially engulf the next generation. We can define regenerative medicine broadly as approaches that use stem cell-based therapies or approaches that seek to modulate inherent neurogenesis. Neurogenesis, although most active during prenatal development, has been shown to continue in several small parts of the brain, including the hippocampus and the subventricular zone, suggesting its potential to reverse cognitive deficits. If AD pathology affects neurogenesis, then it follows that conditions that stimulate endogenous neurogenesis (eg, environmental stimuli, physical activity, trophic factors, cytokines, and drugs) may help to promote the regenerative and recovery process. Herein, we review the complex logistics of potentially implementing neurogenesis-based therapeutic strategies for the treatment of AD. PMID:24286919

  18. Regenerative Medicine in Alzheimer's Disease

    PubMed Central

    Felsenstein, Kevin M.; Candelario, Kate M.; Steindler, Dennis A.; Borchelt, David R.

    2013-01-01

    Identifying novel, effective therapeutics for Alzheimer's disease (AD) is one of the major unmet medical needs for the coming decade. Because the current paradigm for developing and testing disease modifying AD therapies is protracted and likely to be even longer with the shift towards earlier intervention in pre-clinical AD, it is an open question whether we can develop, test, and widely deploy a novel therapy in time to help the current at-risk generation if we continue to follow the standard paradigms of discovery and drug development. There is an imperative need to find safe and effective preventative measures that can be rapidly deployed to stem the coming wave of AD that will potentially engulf the next generation. We can broadly define regenerative medicine as approaches that use stem-cell-based therapies or approaches that seek to modulate inherent neurogenesis. Neurogenesis, though most active during pre-natal development has been shown to continue in several small parts of the brain, which includes the hippocampus and the subventricular zone, suggesting its potential to reverse cognitive deficits. If AD pathology impacts neurogenesis then it follows that conditions that stimulate endogenous neurogenesis (e.g., environmental stimuli, physical activity, trophic factors, cytokines, and drugs) may help to promote the regenerative and recovery process. Herein, we review the complex logistics of potentially implementing neurogenesis-based therapeutic strategies for the treatment of AD. PMID:24286919

  19. 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…

  20. Deterioration in donepezil-induced PR prolongation after a coadministration of memantine in a patient with Alzheimer's disease.

    PubMed

    Igeta, Hirofumi; Suzuki, Yutaro; Motegi, Takaharu; Sasaki, Aiko; Yokoyama, Yuichi; Someya, Toshiyuki

    2013-01-01

    The side effects and interaction of memantine and donepezil hydrochloride when used concomitantly are currently unknown. We encountered a case of a 77-year-old female with Alzheimer's disease in which the concomitant use of memantine exacerbated the prolonged electrocardiogram PR interval which appeared while donepezil hydrochloride was being orally administered. In terms of the cardiac circulation system side effects caused by donepezil hydrochloride and memantine, bradycardia has been reported. However, clinicians should be also aware of PR prolongation associated with the concomitant use of donepezil and memantine.

  1. Comprehension of Long Distance Number Agreement in Probable Alzheimer's Disease.

    ERIC Educational Resources Information Center

    Almor, Amit; MacDonald, Maryellen C.; Kempler, Daniel; Andersen, Elaine S.; Tyler, Lorraine K.

    2001-01-01

    Two studies are discussed. The first tested the effect of intervening material on the processing of subject-verb number agreement in Alzheimer's Disease patients and in normal elderly adults. The second examined the effect of intervening material on the processing of pronoun-antecedent number agreement in the same patients. (Author/VWL)

  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. 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

  4. 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

  5. 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

  6. LDL-lipids from patients with hypercholesterolaemia and Alzheimer's disease are inflammatory to microvascular endothelial cells: mitigation by statin intervention.

    PubMed

    Dias, H K Irundika; Brown, Caroline L R; Polidori, M Cristina; Lip, Gregory Y H; Griffiths, Helen R

    2015-12-01

    Elevated low-density lipoprotein (LDL) concentration in mid-life increases the risk of developing Alzheimer's disease (AD) in later life. Increased oxidized LDL (oxLDL) modification and nitration is observed during dementia and hypercholesterolaemia. We investigated the hypothesis that statin intervention in mid-life mitigates the inflammatory effects of oxLDL on the microvasculature. Human microvascular endothelial cells (HMVECs) were maintained in transwells to mimic the microvasculature and exposed to patient and control LDL. Blood was obtained from statin-naive, normo- and hyper-lipidaemic subjects, AD with vascular dementia (AD-plus) and AD subjects (n=10/group) at baseline. Only hyperlipidaemic subjects with normal cognitive function received 40 mg of simvastatin intervention/day for 3 months. Blood was re-analysed from normo- and hyper-lipidaemic subjects after 3 months. LDL isolated from statin-naive hyperlipidaemic, AD and AD-plus subjects was more oxidized (agarose gel electrophoretic mobility, protein carbonyl content and 8-isoprostane F2α) compared with control subjects. Statin intervention decreased protein carbonyls (2.5±0.4 compared with 3.95±0.2 nmol/mg; P<0.001) and 8-isoprostane F2α (30.4±4.0 pg/ml compared with 43.5±8.42 pg/ml; P<0.05). HMVEC treatment with LDL-lipids (LDL-L) from hyperlipidaemic, AD and AD-plus subjects impaired endothelial tight junction expression and decreased total glutathione levels (AD; 18.61±1.3, AD-plus; 16.5±0.7 nmol/mg of protein) compared with untreated cells (23.8±1.2 compared with nmol/mg of protein). Basolateral interleukin (IL)-6 secretion was increased by LDL-L from hyperlipidaemic (78.4±1.9 pg/ml), AD (63.2±5.9 pg/ml) and AD-plus (80.8±0.9 pg/ml) groups compared with healthy subject lipids (18.6±3.6 pg/ml). LDL-L isolated after statin intervention did not affect endothelial function. In summary, LDL-L from hypercholesterolaemic, AD and AD-plus patients are inflammatory to HMVECs. In vivo

  7. LDL-lipids from patients with hypercholesterolaemia and Alzheimer's disease are inflammatory to microvascular endothelial cells: mitigation by statin intervention.

    PubMed

    Dias, H K Irundika; Brown, Caroline L R; Polidori, M Cristina; Lip, Gregory Y H; Griffiths, Helen R

    2015-12-01

    Elevated low-density lipoprotein (LDL) concentration in mid-life increases the risk of developing Alzheimer's disease (AD) in later life. Increased oxidized LDL (oxLDL) modification and nitration is observed during dementia and hypercholesterolaemia. We investigated the hypothesis that statin intervention in mid-life mitigates the inflammatory effects of oxLDL on the microvasculature. Human microvascular endothelial cells (HMVECs) were maintained in transwells to mimic the microvasculature and exposed to patient and control LDL. Blood was obtained from statin-naive, normo- and hyper-lipidaemic subjects, AD with vascular dementia (AD-plus) and AD subjects (n=10/group) at baseline. Only hyperlipidaemic subjects with normal cognitive function received 40 mg of simvastatin intervention/day for 3 months. Blood was re-analysed from normo- and hyper-lipidaemic subjects after 3 months. LDL isolated from statin-naive hyperlipidaemic, AD and AD-plus subjects was more oxidized (agarose gel electrophoretic mobility, protein carbonyl content and 8-isoprostane F2α) compared with control subjects. Statin intervention decreased protein carbonyls (2.5±0.4 compared with 3.95±0.2 nmol/mg; P<0.001) and 8-isoprostane F2α (30.4±4.0 pg/ml compared with 43.5±8.42 pg/ml; P<0.05). HMVEC treatment with LDL-lipids (LDL-L) from hyperlipidaemic, AD and AD-plus subjects impaired endothelial tight junction expression and decreased total glutathione levels (AD; 18.61±1.3, AD-plus; 16.5±0.7 nmol/mg of protein) compared with untreated cells (23.8±1.2 compared with nmol/mg of protein). Basolateral interleukin (IL)-6 secretion was increased by LDL-L from hyperlipidaemic (78.4±1.9 pg/ml), AD (63.2±5.9 pg/ml) and AD-plus (80.8±0.9 pg/ml) groups compared with healthy subject lipids (18.6±3.6 pg/ml). LDL-L isolated after statin intervention did not affect endothelial function. In summary, LDL-L from hypercholesterolaemic, AD and AD-plus patients are inflammatory to HMVECs. In vivo

  8. 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.

  9. Aroma and taste perceptions with Alzheimer disease and stroke.

    PubMed

    Aliani, Michel; Udenigwe, Chibuike C; Girgih, Abraham T; Pownall, Trisha L; Bugera, Jacqeline L; Eskin, Michael N A

    2013-01-01

    Chemosensory disorders of smell or taste in humans have been attributed to various physiological and environmental factors including aging and disease conditions. Aroma and taste greatly condition our food preference, selection and, consumption; the decreased appetite in patients with known neurodegenerative diseases may lead to dietary restrictions that could negatively impact nutritional and health status. The decline in olfactory and gustatory systems in patients with Alzheimer disease and various types of stroke are described.

  10. Memory for music in Alzheimer's disease: unforgettable?

    PubMed

    Baird, Amee; Samson, Séverine

    2009-03-01

    The notion that memory for music can be preserved in patients with Alzheimer's Disease (AD) has been raised by a number of case studies. In this paper, we review the current research examining musical memory in patients with AD. In keeping with models of memory described in the non-musical domain, we propose that various forms of musical memory exist, and may be differentially impaired in AD, reflecting the pattern of neuropathological changes associated with the condition. Our synthesis of this literature reveals a dissociation between explicit and implicit musical memory functions. Implicit, specifically procedural musical memory, or the ability to play a musical instrument, can be spared in musicians with AD. In contrast, explicit musical memory, or the recognition of familiar or unfamiliar melodies, is typically impaired. Thus, the notion that music is unforgettable in AD is not wholly supported. Rather, it appears that the ability to play a musical instrument may be unforgettable in some musicians with AD. PMID:19214750

  11. Memory for music in Alzheimer's disease: unforgettable?

    PubMed

    Baird, Amee; Samson, Séverine

    2009-03-01

    The notion that memory for music can be preserved in patients with Alzheimer's Disease (AD) has been raised by a number of case studies. In this paper, we review the current research examining musical memory in patients with AD. In keeping with models of memory described in the non-musical domain, we propose that various forms of musical memory exist, and may be differentially impaired in AD, reflecting the pattern of neuropathological changes associated with the condition. Our synthesis of this literature reveals a dissociation between explicit and implicit musical memory functions. Implicit, specifically procedural musical memory, or the ability to play a musical instrument, can be spared in musicians with AD. In contrast, explicit musical memory, or the recognition of familiar or unfamiliar melodies, is typically impaired. Thus, the notion that music is unforgettable in AD is not wholly supported. Rather, it appears that the ability to play a musical instrument may be unforgettable in some musicians with AD.

  12. 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. PMID:20406252

  13. An anemia of Alzheimer's disease.

    PubMed

    Faux, N G; Rembach, A; Wiley, J; Ellis, K A; Ames, D; Fowler, C J; Martins, R N; Pertile, K K; Rumble, R L; Trounson, B; Masters, C L; Bush, A I

    2014-11-01

    Lower hemoglobin is associated with cognitive impairment and Alzheimer's disease (AD). Since brain iron homeostasis is perturbed in AD, we investigated whether this is peripherally reflected in the hematological and related blood chemistry values from the Australian Imaging Biomarker and Lifestyle (AIBL) study (a community-based, cross-sectional cohort comprising 768 healthy controls (HC), 133 participants with mild cognitive impairment (MCI) and 211 participants with AD). We found that individuals with AD had significantly lower hemoglobin, mean cell hemoglobin concentrations, packed cell volume and higher erythrocyte sedimentation rates (adjusted for age, gender, APOE-ɛ4 and site). In AD, plasma iron, transferrin, transferrin saturation and red cell folate levels exhibited a significant distortion of their customary relationship to hemoglobin levels. There was a strong association between anemia and AD (adjusted odds ratio (OR)=2.43, confidence interval (CI) (1.31, 4.54)). Moreover, AD emerged as a strong risk factor for anemia on step-down regression, even when controlling for all other available explanations for anemia (adjusted OR=3.41, 95% CI (1.68, 6.92)). These data indicated that AD is complicated by anemia, which may itself contribute to cognitive decline. PMID:24419041

  14. 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.

  15. 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

  16. Inhalational Alzheimer's disease: an unrecognized - and treatable - epidemic.

    PubMed

    Bredesen, Dale E

    2016-02-01

    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

  17. 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. PMID:14681160

  18. 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,…

  19. 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. PMID:18580596

  20. 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

  1. 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

  2. No effect of the α1-antichymotrypsin A allele in Alzheimer's disease

    PubMed Central

    Didierjean, O; Martinez, M; Campion, D; Hannequin, D; Dubois, B; Martin, C; Puel, M; Anterion, C; Pasquier, F; Moreau, O; Babron, M; Penet, C; Agid, Y; Clerget-Darpoux, F; Frebourg, T; Brice, A

    1997-01-01

    The apolipoprotein E (ApoE)-ε4 allele is associated in a dose dependent manner to an increased risk for Alzheimer's disease. However, the ApoE-ε4 allele effect does not account for all patients with Alzheimer's disease, and the existence of other genetic risk factors has been postulated. Kamboh et al reported an association between Alzheimer's disease and the A allele of α1-antichymotrypsin (Aact) gene, which was not confirmed in a larger series more recently analysed. The ApoE and Aact genotypes were analysed in 314 patients with Alzheimer's disease and 173 healthy controls, confirming the dose dependent effect of the ApoE-ε4 allele. Nevertheless, even using odds ratios adjusted for age and sex, there was no significant effect of the Aact genotype on Alzheimer's disease or on the ApoE-ε4 allele associated risk for Alzheimer's disease.

 PMID:9221977

  3. Sleep disturbances in Alzheimer's and Parkinson's diseases.

    PubMed

    Rothman, Sarah M; Mattson, Mark P

    2012-09-01

    Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders and exact a burden on our society greater than cardiovascular disease and cancer combined. While cognitive and motor symptoms are used to define AD and PD, respectively, patients with both disorders exhibit sleep disturbances including insomnia, hypersomnia and excessive daytime napping. The molecular basis of perturbed sleep in AD and PD may involve damage to hypothalamic and brainstem nuclei that control sleep-wake cycles. Perturbations in neurotransmitter and hormone signaling (e.g., serotonin, norepinephrine and melatonin) and the neurotrophic factor BDNF likely contribute to the disease process. Abnormal accumulations of neurotoxic forms of amyloid β-peptide, tau and α-synuclein occur in brain regions involved in the regulation of sleep in AD and PD patients, and are sufficient to cause sleep disturbances in animal models of these neurodegenerative disorders. Disturbed regulation of sleep often occurs early in the course of AD and PD, and may contribute to the cognitive and motor symptoms. Treatments that target signaling pathways that control sleep have been shown to retard the disease process in animal models of AD and PD, suggesting a potential for such interventions in humans at risk for or in the early stages of these disorders. PMID:22552887

  4. Absence of aluminium in neuritic plaque cores in Alzheimer's disease.

    PubMed

    Landsberg, J P; McDonald, B; Watt, F

    1992-11-01

    Controversy exists over whether aluminium has a role in the aetiology of Alzheimer's disease. Alzheimer's disease is neuropathologically characterized by the occurrence of a minimum density of neurofibrillary tangles and neuritic plaques in the hippocampus and the association cortex of the brain. The purported association of aluminium with Alzheimer's disease is based on: (1) the experimental induction of fibrillary changes in the neurons of animals by the injection of aluminium salts into brain tissue; (2) reported detection of aluminium in neuritic plaques and tangle-bearing neurons; (3) epidemiological studies linking aluminium levels in the environment, notably water supplies, with an increased prevalence of dementia; and (4) a reported decrease in the rate of disease progression following the administration of desferroxamine, an aluminium chelator, to clinically diagnosed sufferers of Alzheimer's disease. Here we use nuclear microscopy, a new analytical technique involving million-volt nuclear particles, to identify and analyse plaques in postmortem tissue from patients with Alzheimer's disease without using chemical staining techniques and fail to demonstrate the presence of aluminium in plaque cores in untreated tissue. PMID:1436075

  5. 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.

  6. Differential efficacy of treatment with acetylcholinesterase inhibitors in patients with mild and moderate Alzheimer's disease over a 6-month period.

    PubMed

    López-Pousa, S; Turon-Estrada, A; Garre-Olmo, J; Pericot-Nierga, I; Lozano-Gallego, M; Vilalta-Franch, M; Hernández-Ferràndiz, M; Morante-Muñoz, V; Isern-Vila, A; Gelada-Batlle, E; Majó-Llopart, J

    2005-01-01

    There are various anticholinesterase inhibitors (AChEIs) for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). All AChEIs have shown greater efficacy than placebo in randomized, double-blind, parallel-group clinical trials. No differential studies have yet been made of the efficacy between all AChEIs. The study aims to determine the differential efficacy of the AChEIs with respect to a historical sample of patients with AD that were not treated with AChEIs. An open-label, prospective, observational study with a retrospective control group was undertaken to examine the evolution of the cognitive function over a 6-month period. The patients were assessed with the Mini-Mental State Examination (MMSE) at study entry and at 6 months. A general linear model was applied for repeated measurements with the MMSE score as the dependent variable, treatment type as an independent variable and the severity of the deterioration, age and the MMSE baseline score as covariables. Of the sample of 147 patients, 40 initiated treatment with donepezil, 32 with galantamine, 30 with rivastigmine and 45 were part of a historical sample of the memory clinic patients between 1991 and 1996 that had not been treated with AChEIs. The average age was 73.7 years (SD = 6.9; range = 52-86), 67.3% were women, 78.2% of the cases were mild and the MMSE baseline score was 18.1 points (range = 11-27). No significant intergroup differences were observed in these variables. The average doses of donepezil, galantamine and rivastigmine were 5.87 mg/day (SD = 1.92), 14.81 mg/day (SD = 6.25) and 6.41 mg/day (SD = 1.82), respectively. At 6 months, the difference in the MMSE score with respect to the untreated group was 1.6 points for donepezil (95% CI 0.79-2.37; p < 0.001), 0.99 points for galantamine (95% CI 0.14-1.85; p = 0.01) and 0.90 points for rivastigmine (95% CI 0.05-1.74; p = 0.03). No significant differences were observed in the efficacy among the groups treated with AChEIs (p

  7. Aluminium and Alzheimer's disease: An epidemiological approach.

    PubMed

    Martyn, C N

    1990-03-01

    Epidemiological methods have an important role in the investigation of the postulated connection between exposure to aluminium and the development of Alzheimer's disease. We have examined the usefulness of existing data on prevalence and mortality as a resource for studying variations in the rate of the disease with time and geography. Unfortunately, methodological differences between prevalence surveys and errors and biases in mortality data are large. No reliable conclusions can be drawn from these data about geographical differences in rates of dementia in England and Wales nor about time trends in the disease.Aluminium salts are widely used in the UK for the treatment of drinking water. Residual aluminium concentrations vary more than ten fold between different parts of the country. We have estimated diagnostic rates of pre-senile Alzheimer's disease in seven geographical areas and examined the correlation between rates of Alzheimer's disease and water aluminium concentration. PMID:24202582

  8. Changes in chromatin structure associated with Alzheimer's disease.

    PubMed

    Lewis, P N; Lukiw, W J; De Boni, U; McLachlan, D R

    1981-11-01

    The enzyme micrococcal nuclease was used to examine the accessibility of chromatin extracted from brains of 13 patients with senile and presenile dementia of the Alzheimer type. Compared with chromatin extracted from brains of 8 patients without neurological signs or brain pathology and brains of 7 patients with nonAlzheimer dementia, Alzheimer chromatin was less accessible to this enzyme. Reduced accessibility was reflected by a reduced yield of mononucleosomes in comparison with dinucleosomes and larger oligomers. Both neuronal and glial chromatin were found to be similarly affected. The reduced yield of mononucleosomes from Alzheimer chromatin is not due to their increased breakdown, but is probably related to protein associated with the internucleosomal linker region that retards nuclease action. Dinucleosomes isolated from control and Alzheimer nuclease digests were examined for their protein complement. Three perchloric acid-soluble proteins situated in the histone H1 region of sodium dodecyl sulfate (SDS) gels were present in elevated levels in Alzheimer dinucleosomes. These results represent the first example of altered chromosomal proteins associated with a diseased state of the brain.

  9. 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).

  10. The micron stroke hypothesis of Alzheimer's disease and dementia.

    PubMed

    Orehek, Allen J

    2012-05-01

    Alzheimer's disease as currently described in the medical literature is often more a description of dementia rather than a specific disease. In over a century of scientific work there has been no proven theory as to the precise pathogenesis of Alzheimer's disease and dementia. As there is no efficient treatment for patients with Alzheimer's disease, prevention or attenuation of the disease is of substantial value. An intricate collection of hypotheses, studies, research, and experience has made it complicated for one to completely understand this disease. The purpose of this hypothesis is to illustrate new concepts and work to link those concepts to the present understanding of an obscure disease. The search for a single unifying hypothesis on the etiology of Alzheimer's disease has been elusive. Many hypotheses associated to Alzheimer's disease have not survived their testing to become theory. Suggested here is that the elusive nature of etiology of dementia is not from one cause, but rather the causes are numerous. Medical terminology used freely for decades is rarely evaluated in the light of a new hypothesis. At the foundation of this work is the suggestion of a new medical term: Micron Strokes. The Micron Stroke Hypothesis of Alzheimer's Disease and Dementia include primary and secondary factors. The primary factors can be briefly described as baseline brain tissue, atrial fibrillation, hypercoaguable state, LDL, carotid artery stenosis, tobacco exposure, hypertension diabetes mellitus, and the presence of systemic inflammation. Dozens of secondary factors contribute to the development of dementia. Most dementia is caused by nine primary categories of factors as they interact to cause micron strokes to the brain.

  11. 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.

  12. 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.

  13. 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.

  14. Adding Memantine to Rivastigmine Therapy in Patients With Mild-to-Moderate Alzheimer's Disease: Results of a 12-Week, Open-Label Pilot Study

    PubMed Central

    Riepe, Matthias W.; Adler, Georg; Ibach, Bernd; Weinkauf, Birgit; Gunay, Ibrahim; Tracik, Ferenc

    2006-01-01

    Objective: At present, inhibition of cholines-terase is the treatment of choice for subjects with mild-to-moderate Alzheimer's disease (AD). Memantine, a noncompetitive antagonist at N-methyl-d-aspartate receptors, is currently used to treat subjects with moderate-to-severe AD. The goal of this multicenter, open-label pilot study was to investigate whether combination therapy with memantine added to rivastigmine is safe and beneficial in subjects with mild-to-moderate AD. Method: Patients with a DSM-IV diagnosis of dementia of the Alzheimer's type (N = 95), who were treated with rivastigmine (6–12 mg/day) for a maximum duration of 24 weeks prior to baseline, received memantine (5–20 mg/day) in combination with rivastigmine for 12 weeks. The primary efficacy variable was the change in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total score at the end of 12 weeks compared with baseline. The study was conducted between September 15, 2003, and May 27, 2004. Results: There was a statistically significant difference between baseline and week 12 for the ADAS-cog total score, showing a positive effect of combination therapy. Combination therapy did not evidence any unexpected safety concerns and was well-tolerated by most patients. Conclusion: Memantine in combination with rivastigmine appears to be safe and beneficial in patients with mild-to-moderate AD. Our results need to be confirmed in a large, long-term, randomized, double-blind, placebo-controlled clinical trial. PMID:17235381

  15. Potential Role of Aminoprocalcitonin in the Pathogenesis of Alzheimer Disease.

    PubMed

    Tavares, Eva; Antequera, Desiree; López-González, Irene; Ferrer, Isidro; Miñano, Francisco J; Carro, Eva

    2016-10-01

    Increasing evidence suggests that inflammatory responses cause brain atrophy and play a prominent and early role in the progression of Alzheimer disease. Recent findings show that the neuroendocrine peptide aminoprocalcitonin (NPCT) plays a critical role in the development of systemic inflammatory response; however, the presence, possible function, regulation, and mechanisms by which NPCT may be involved in Alzheimer disease neuropathology remain unknown. We explored the expression of NPCT and its interaction with amyloid-β (Aβ), and proinflammatory and neurogenic effects. By using brain samples of Alzheimer disease patients and APP/PS1 transgenic mice, we evaluated the potential role of NPCT on Aβ-related pathology. We found that NPCT is expressed in hippocampal and cortical neurons and Aβ-induced up-regulation of NPCT expression. Peripherally administered antibodies against NPCT decreased microglial activation, decreased circulating levels of proinflammatory cytokines, and prevented Aβ-induced neurotoxicity in experimental models of Alzheimer disease. Remarkably, anti-NPTC therapy resulted in a significant improvement in the behavioral status of APP/PS1 mice. Our results indicate a central role of NPCT in Alzheimer disease pathogenesis and suggest NPCT as a potential biomarker and therapeutic target. PMID:27497681

  16. Memantine Attenuates Alzheimer's Disease-Like Pathology and Cognitive Impairment.

    PubMed

    Wang, Xiaochuan; Blanchard, Julie; Grundke-Iqbal, Inge; Iqbal, Khalid

    2015-01-01

    Deficiency of protein phosphatase-2A is a key event in Alzheimer's disease. An endogenous inhibitor of protein phosphatase-2A, inhibitor-1, I1PP2A, which inhibits the phosphatase activity by interacting with its catalytic subunit protein phosphatase-2Ac, is known to be upregulated in Alzheimer's disease brain. In the present study, we overexpressed I1PP2A by intracerebroventricular injection with adeno-associated virus vector-1-I1PP2A in Wistar rats. The I1PP2A rats showed a decrease in brain protein phosphatase-2A activity, abnormal hyperphosphorylation of tau, neurodegeneration, an increase in the level of activated glycogen synthase kinase-3beta, enhanced expression of intraneuronal amyloid-beta and spatial reference memory deficit; littermates treated identically but with vector only, i.e., adeno-associated virus vector-1-enhanced GFP, served as a control. Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer's disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer's disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1PP2A rats. These findings provide new clues into the possible mechanism of the beneficial therapeutic effect of memantine in Alzheimer's disease patients.

  17. Potential Role of Aminoprocalcitonin in the Pathogenesis of Alzheimer Disease.

    PubMed

    Tavares, Eva; Antequera, Desiree; López-González, Irene; Ferrer, Isidro; Miñano, Francisco J; Carro, Eva

    2016-10-01

    Increasing evidence suggests that inflammatory responses cause brain atrophy and play a prominent and early role in the progression of Alzheimer disease. Recent findings show that the neuroendocrine peptide aminoprocalcitonin (NPCT) plays a critical role in the development of systemic inflammatory response; however, the presence, possible function, regulation, and mechanisms by which NPCT may be involved in Alzheimer disease neuropathology remain unknown. We explored the expression of NPCT and its interaction with amyloid-β (Aβ), and proinflammatory and neurogenic effects. By using brain samples of Alzheimer disease patients and APP/PS1 transgenic mice, we evaluated the potential role of NPCT on Aβ-related pathology. We found that NPCT is expressed in hippocampal and cortical neurons and Aβ-induced up-regulation of NPCT expression. Peripherally administered antibodies against NPCT decreased microglial activation, decreased circulating levels of proinflammatory cytokines, and prevented Aβ-induced neurotoxicity in experimental models of Alzheimer disease. Remarkably, anti-NPTC therapy resulted in a significant improvement in the behavioral status of APP/PS1 mice. Our results indicate a central role of NPCT in Alzheimer disease pathogenesis and suggest NPCT as a potential biomarker and therapeutic target.

  18. 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

  19. 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

  20. Cannabinoids in late-onset Alzheimer's disease.

    PubMed

    Ahmed, Aia; van der Marck, M A; van den Elsen, Gah; Olde Rikkert, Mgm

    2015-06-01

    Given the lack of effective treatments for late-onset Alzheimer's disease (LOAD) and the substantial burden on patients, families, health care systems, and economies, finding an effective therapy is one of the highest medical priorities. The past few years have seen a growing interest in the medicinal uses of cannabinoids, the bioactive components of the cannabis plant, including the treatment of LOAD and other physical conditions that are common in older people. Several in vitro and in vivo studies have demonstrated that cannabinoids can reduce oxidative stress, neuroinflammation, and the formation of amyloid plaques and neurofibrillary tangles, the key hallmarks of LOAD. In addition, in population-based studies, cannabinoids reduced dementia-related symptoms (e.g., behavioral disturbances). The current article provides an overview of the potential of cannabinoids in the treatment of LOAD and related neuropsychiatric symptoms in older people. We also discuss the efficacy, safety, and pharmacokinetics of cannabinoid-based drugs in older people with dementia.

  1. 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. PMID:23904110

  2. Alzheimer's disease care and management: role of information technology.

    PubMed

    Thota, Hanuman; Rao, Allam Appa; Reddi, Kiran Kumar; Akula, Sivaprasad; Changalasetty, Suresh Babu; Srinubabu, Gedela

    2007-01-01

    Alzheimer's disease (AD) an ailment that is supposed to affect people in old age. There are evidences that it might affect others also. The number of elders is increasing as the average life expectancy is increasing. AD afflicts its patients with the dementia and AD might increase in malignance over time. People with cognitive disabilities can be overwhelmed through cognitive prosthetics. With the help of information technology we can enhance the quality of life. Significant achievements are possible with an interdisciplinary approach that includes genomic, genetic, technological and therapeutic measures. The combination and coordination of Bioinformatics facilitates generation of various diagnostic tools for the people who are suffering from Alzheimer's disease. These tools help the care providers also. In this article, we emphasize the literature regarding the use of technology and its methodologies to improve the quality of care for the people with Alzheimer's disease.

  3. 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…

  4. 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…

  5. 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…

  6. Effects of an elastic band resistance exercise program on lower extremity muscle strength and gait ability in patients with Alzheimer's disease.

    PubMed

    Ahn, Nayoung; Kim, Kijin

    2015-06-01

    [Purpose] This study examined the effects of a resistance exercise programs aiming to improve muscular function in order to prevent and treat Alzheimer's disease in elderly people. [Subjects and Methods] Elderly patients with mild dementia were randomly assigned to an elastic band resistance exercise group (74.21±6.09 years). The experimental group (n=23) performed upper and lower extremity exercises three times per week for five months. Physical fitness was measured according to chair leg squat, one-leg stance, timed up-and-go test, 2-minute walking test, and gait ability before and after exercise. [Results] Static balance ability in which the participant stood on one foot with eyes open (left and right) increased significantly, but the dynamic balancing ability in the timed up-and-go test did not improve significantly. Cardiorespiratory function and gait speed improved significantly. [Conclusion] The five-month elastic band resistance exercise program improved muscle strength and endurance, cardiovascular function, and gait speed. Therefore, it may be an effective rehabilitation program for elderly patients with Alzheimer's disease. PMID:26180356

  7. Is Alzheimer's disease a homogeneous disease entity?

    PubMed

    Korczyn, Amos D

    2013-10-01

    The epidemic proportions of dementia in old age are a cause of great concern for the medical profession and the society at large. It is customary to consider Alzheimer's disease (AD) as the most common cause of dementia, and vascular dementia (VaD) as being the second. This dichotomous view of a primary neurodegenerative disease as opposed to a disorder where extrinsic factors cause brain damage led to separate lines of research in these two entities. New biomarkers, particularly the introduction of modern neuroimaging and cerebrospinal fluid changes, have, in recent years, helped to identify anatomical and chemical changes of VaD and of AD. Nevertheless, there is a substantial difference between the two entities. While it is clear that VaD is a heterogeneous entity, AD is supposed to be a single disorder. Nobody attempts to use CADASIL as a template to develops treatment for sporadic VaD. On the other hand, early-onset AD is used to develop therapy for sporadic AD. This paper will discuss the problems relating to this false concept and its consequences. PMID:23933662

  8. Recommended minimum data to be collected in research studies on Alzheimer's disease. The MRC (UK) Alzheimer's Disease Workshop Steering Committee.

    PubMed Central

    Wilcock, G K; Hope, R A; Brooks, D N; Lantos, P L; Oppenheimer, C; Reynolds, G P; Rossor, M N; Davies, M B

    1989-01-01

    In order to be able to compare the results of research work carried out in different centres on Alzheimer's disease and dementia, it is necessary for there to be standardised assessment methods. The Medical Research Council organised a workshop in order to see whether workers in Britain in the field of dementia research could agree on such standardised assessment methods. The workshop agreed guidelines for the minimum data which should be collected, in clinical and pathological studies, on patients with presumed Alzheimer's disease and dementia. These recommendations are compared with other approaches based on research diagnostic criteria. PMID:2664087

  9. Alzheimer's disease drug development: translational neuroscience strategies.

    PubMed

    Cummings, Jeffrey L; Banks, Sarah J; Gary, Ronald K; Kinney, Jefferson W; Lombardo, Joseph M; Walsh, Ryan R; Zhong, Kate

    2013-06-01

    Alzheimer's disease (AD) is an urgent public health challenge that is rapidly approaching epidemic proportions. New therapies that defer or prevent the onset, delay the decline, or improve the symptoms are urgently needed. All phase 3 drug development programs for disease-modifying agents have failed thus far. New approaches to drug development are needed. Translational neuroscience focuses on the linkages between basic neuroscience and the development of new diagnostic and therapeutic products that will improve the lives of patients or prevent the occurrence of brain disorders. Translational neuroscience includes new preclinical models that may better predict human efficacy and safety, improved clinical trial designs and outcomes that will accelerate drug development, and the use of biomarkers to more rapidly provide information regarding the effects of drugs on the underlying disease biology. Early translational research is complemented by later stage translational approaches regarding how best to use evidence to impact clinical practice and to assess the influence of new treatments on the public health. Funding of translational research is evolving with an increased emphasis on academic and NIH involvement in drug development. Translational neuroscience provides a framework for advancing development of new therapies for AD patients.

  10. 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

  11. Transcription factor NF-κB is activated in primary neurons by amyloid β peptides and in neurons surrounding early plaques from patients with Alzheimer disease

    PubMed Central

    Kaltschmidt, Barbara; Uherek, Martin; Volk, Benedikt; Baeuerle, Patrick A.; Kaltschmidt, Christian

    1997-01-01

    Amyloid β peptide (Aβ)-containing plaques are a hallmark of Alzheimer disease. Here, we show that the neurotoxic Aβ, a major plaque component, is a potent activator of the transcription factor NF-κB in primary neurons. This activation required reactive oxygen intermediates as messengers because an antioxidant prevented Aβ-induced NF-κB activation. Maximal activation of NF-κB was found with 0.1 μM Aβ-(1–40) and 0.1 μM Aβ-(25–35) fragments, making a role for NF-κB in neuroprotection feasible. Using an activity-specific mAb for the p65 NF-κB subunit, activation of NF-κB also was observed in neurons and astroglia of brain sections from Alzheimer disease patients. Activated NF-κB was restricted to cells in the close vicinity of early plaques. Our data suggest that the aberrant gene expression in diseased nervous tissue is at least in part due to Aβ-induced activation of NF-κB, a potent immediate–early transcriptional regulator of numerous proinflammatory genes. PMID:9122249

  12. Brainstem morphological changes in Alzheimer's disease.

    PubMed

    Lee, Ji Han; Ryan, John; Andreescu, Carmen; Aizenstein, Howard; Lim, Hyun Kook

    2015-05-01

    As brainstem nuclei are interconnected with several cortical structures and regulate several autonomic, cognitive, and behavioral functions, it might be important to place the brainstem within an important pathologic core in the progression of Alzheimer's disease (AD). Although there have been several postmortem studies reporting neuropathological alterations of the brainstem in AD, there has been no in-vivo structural neuroimaging study of the brainstem in the patients with AD. The aim of this study was to investigate differences in the brainstem volume and shape between patients with AD and elderly normal controls. Fifty AD patients (the Clinical Dementia Rating Scale ≥ 1) and 50 normal controls were recruited, and the brainstem volumes and deformations were compared between the AD and the controls. Patients with AD showed significant total volume [(mean ± SD) 21007 ± 1640 mm] reduction in the brainstem compared with the controls [(mean ± SD) 22530 ± 1750 mm] (P<0.001). In addition, AD patients showed significant brainstem deformations in the upper posterior brainstem corresponding to the midbrain compared with the healthy individuals (false discovery rate corrected P<0.05). This study is the first to explore brainstem volume change and deformations in AD. These structural changes in the midbrain areas might be at the core of the underlying neurobiological mechanisms of brainstem dysfunction with relevance to their various cognitive and behavioral symptoms such as memory impairment, sleep, and emotional disturbance in AD. However, further longitudinal studies might be needed to confirm these findings. PMID:25830491

  13. [Alzheimer's disease: a public health problem: yes, but a priority?].

    PubMed

    Dartigues, J F; Helmer, C; Dubois, B; Duyckaerts, C; Laurent, B; Pasquier, F; Touchon, J

    2002-03-01

    Alzheimer's Disease is a major Public Health problem for many reasons. First, it is a frequent disease since, in France, the prevalence was estimated at about 400.000 cases, and the annual incidence at 100.000 cases. The frequency of the disease increases, in particular due to the ageing of the population. This disease has major consequences on the life of the patient and his/her caretaker. The cost of the disease is important, estimated at about 50 milliards of French francs. Pharmaceutical treatment and other interventions are possible in particular to delay the nursing home placement. On the other hand, this disease is often ignored, under-diagnosed, underestimated and exposed to inequality in resorting to care. In summary, Alzheimer's Disease (AD) has all the criteria required for a major public health problem. In spite of this observation, AD is not yet considered as a priority for health authorities, although attitudes are changing.

  14. 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 ...

  15. 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.

  16. 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.

  17. Explorative and targeted neuroproteomics in Alzheimer's disease.

    PubMed

    Brinkmalm, Ann; Portelius, Erik; Öhrfelt, Annika; Brinkmalm, Gunnar; Andreasson, Ulf; Gobom, Johan; Blennow, Kaj; Zetterberg, Henrik

    2015-07-01

    Alzheimer's disease (AD) is a progressive brain amyloidosis that injures brain regions involved in memory consolidation and other higher brain functions. Neuropathologically, the disease is characterized by accumulation of a 42 amino acid peptide called amyloid β (Aβ42) in extracellular senile plaques, intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles, and neuronal and axonal degeneration and loss. Biomarker assays capturing these pathologies have been developed for use on cerebrospinal fluid samples but there are additional molecular pathways that most likely contribute to the neurodegeneration and full clinical expression of AD. One way of learning more about AD pathogenesis is to identify novel biomarkers for these pathways and examine them in longitudinal studies of patients in different stages of the disease. Here, we discuss targeted proteomic approaches to study AD and AD-related pathologies in closer detail and explorative approaches to discover novel pathways that may contribute to the disease. This article is part of a Special Issue entitled: Neuroproteomics: Applications in neuroscience and neurology.

  18. 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.

  19. Alzheimer's disease: rhythm, timing and music as therapy.

    PubMed

    Aldridge, D

    1994-01-01

    Active music-making provides a form of therapy for the Alzheimer's patient which may stimulate cognitive activities such that areas subject to progressive failure are maintained. Anecdotal evidence suggests that quality of life of Alzheimer's patients is significantly improved with music therapy, accompanied by the overall social benefits of acceptance and sense of belonging gained by communicating with others. Music therapy, when based on clear treatment objectives can reduce the individual prescription of tranquilizing medication, reduce the use of hypnotics and help overall goals of rehabilitation. Mood improvement and self-expression, the stimulation of speech and organisation of mental processes; and sensory stimulation and motor integration are promoted. Given that the rate of deterioration in Alzheimer's disease is not predictable, a series of single case experimental designs would generate valuable empirical data concerning treatment outcome and promote basic research into the timing functions required for the co-ordination of cognition, physiology, motor ability and the integrity of behaviour.

  20. Alzheimer disease immunotherapeutics: then and now.

    PubMed

    Jindal, Harashish; Bhatt, Bhumika; Sk, Shashikantha; Singh Malik, Jagbir

    2014-01-01

    Dementia is a public health priority and one of the major contributors to morbidity and global non-communicable disease burden, thus necessitating the need for significant health-care interventions. Alzheimer disease (AD) is the most common cause of dementia and may contribute to 60-70% of cases. The cause and progression of AD are not well understood but have been thought to be due at least in part to protein misfolding (proteopathy) manifest as plaque accumulation of abnormally folded β-amyloid and tau proteins in brain. There are about 8 million new cases per year. The total number of people with dementia is projected to almost double every 20 years, to 66 million in 2030 and 115 million in 2050. Immunotherapy in AD aimed at β-amyloid covers 2 types of vaccination: active vaccination against Aβ42 in which patients receive injections of the antigen itself, or passive vaccination in which patients receive injections of monoclonal antibodies (mAb) against Aβ42. Three of the peptide vaccines for active immunizations, CAD106, ACC001, and Affitope, are in phase 2 clinical trials. Three of the mAbs solanezumab, gantenerumab, and crenezumab, are or were in phase 2 and 3 clinical studies. While the phase 3 trials failed, one of these may have shown a benefit at least in mild forms of AD. There is a need for a greater initiative in the development of immunotherapeutics. Several avenues have been explored and still to come.

  1. Impairment of homonymous processing in Alzheimer's disease.

    PubMed

    Piccirilli, Massimo; D'Alessandro, Patrizia; Micheletti, Norma; Macone, Sara; Scarponi, Laura; Arcelli, Paola; Petrillo, Stefania Maria; Silvestrini, Mauro; Luzzi, Simona

    2015-08-01

    An important issue in research on language is how concepts are represented and associated with each other in the brain. Many investigations have focused on language ambiguity and the phenomenon of homonymy in which a single lexical item, presenting the same form, is related to different meanings. Our study aims to test the hypothesis that weak association of meaning characterizing homonyms may be especially prone to brain damage. To verify this hypothesis a test of attribution of the meaning of homonymous words, the Humpty Dumpty (HD) test, was applied to 50 patients with Alzheimer's disease (AD) and 50 healthy subjects. Results show that AD patients are impaired in the HD test in an early phase of disease and that performance correlates with naming ability and phonological fluency. The data are in keeping with a growing body of literature that supports dual impairment to the semantic system in AD, i.e., to semantic knowledge and active processing and access to the semantic field. The evaluation of the ability to resolve homonymous ambiguity, using the HD test, may provide a useful and quick clinical tool to detect the anomalies of the semantic network linked to either a loss of the core system where meaning of words is stored or an impairment of the access to an intact semantic representation.

  2. Ethical issues in Alzheimer's disease: an overview.

    PubMed

    Leuzy, Antoine; Gauthier, Serge

    2012-05-01

    Alzheimer's disease (AD) accounts for the majority of dementia cases and leaves clinicians, patients, family members, caregivers, and researchers faced with numerous ethical issues that vary and evolve as a function of disease stage and severity. While the disclosure of a diagnosis of AD dementia is difficult enough, advances in the neurobiology of AD--embodied in the recent revisions to the AD diagnostic guidelines--have translated into an increasing shift toward the diagnosis being made in its pre-dementia stages, when patients have full insight into their prognosis. Genetic issues in AD are significant in the case of rare families with an early onset (before age 65) form of the disease, owing to the presence of deterministic mutations. While genetic testing for the apolipoprotein E (APOE) gene--a risk factor for sporadic AD--is widely debated, it may become necessary in the context of novel disease-modifying drugs. The current symptomatic drugs--cholinesterase inhibitors (CIs) and the NMDA receptor antagonist memantine--are relatively simple to use but their access is limited in many countries by economic considerations and therapeutic nihilism. Although their efficacy is modest, they influence the design of protocols for new drugs since placebo treatment in clinical trials involving patients with established dementia is rarely allowed beyond 3 months. Driving privileges are lost in the moderate stages of dementia, with this decision ideally reached using a standardized assessment algorithm. Physical restraints are still overused in moderate-to-severe stages, but the alternative non-pharmacological therapies and caregiver training programs are not yet fully validated using randomized studies. End-of-life care is slowly moving towards a palliative care approach similar to that for end-stage cancer. There will be new drugs in the near future, some of which will delay progression from prodromal stages to dementia, but their use will require careful stopping rules

  3. Qualitative neuropsychological performance characteristics in frontotemporal dementia and Alzheimer's disease

    PubMed Central

    Thompson, J; Stopford, C; Snowden, J; Neary, D

    2005-01-01

    Background: Frontotemporal dementia (FTD) and Alzheimer's disease are clinically distinct disorders, yet neuropsychological studies have had variable success in distinguishing them. A possible reason is that studies typically rely on overall accuracy scores, which may obscure differences in reasons for failure. Objectives: To explore the hypothesis that analysis of qualitative performance characteristics and error types, in addition to overall numerical scores, would enhance the neuropsychological distinction between FTD and Alzheimer's disease. Methods: 38 patients with FTD and 73 with Alzheimer's disease underwent assessment of language, visuospatial abilities, memory, and executive function, using a neuropsychological screening instrument and standard neuropsychological tests. In each of these cognitive domains, performance characteristics and error types were documented, in addition to numerical scores on tests. Results: Whereas comparison of neuropsychological test scores revealed some group differences, these did not occur consistently across tests within cognitive domains. However, analysis of performance characteristics and error types revealed qualitative differences between the two groups. In particular, FTD patients displayed features associated with frontal lobe dysfunction, such as concrete thought, perseveration, confabulation, and poor organisation, which disrupted performance across the range of neuropsychological tests. Conclusions: Numerical scores on neuropsychological tests alone are of limited value in differentiating FTD and Alzheimer's disease, but performance characteristics and error types enhance the distinction between the two disorders. FTD is associated with a profound behavioural syndrome that affects performance on cognitive assessment, obscuring group differences. Qualitative information should be included in neuropsychological research and clinical assessments. PMID:15965196

  4. 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.

  5. 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.

  6. White Matter Lesion Load Is Associated With Resting State Functional MRI Activity and Amyloid PET but not FDG in Mild Cognitive Impairment and Early Alzheimer's Disease Patients

    PubMed Central

    Zhou, Yongxia; Yu, Fang; Duong, Timothy Q.

    2014-01-01

    Purpose To quantify and investigate the interactions between multimodal MRI/positron emission tomography (PET) imaging metrics in elderly patients with early Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy controls. Materials and Methods Thirteen early AD, 17 MCI patients, and 14 age-matched healthy aging controls from the Alzheimer's Disease Neuroimaging Initiative database were selected based on availability of data. Default mode network (DMN) functional connectivity and fractional amplitude of low frequency fluctuation (fALFF) were obtained for resting state functional MRI (RS-fMRI). White matter lesion load (WMLL) was quantified from MRI T2-weighted FLAIR images. Amyloid deposition with PET [18F]-Florbetapir tracer and metabolism of glucose by means of [18F]-fluoro-2-deoxyglucose (FDG) images were quantified using ratio of standard uptake values (rSUV). Results Whole-brain WMLL and amyloid deposition were significantly higher (P < 0.005) in MCI and AD patients compared with controls. RS-fMRI results showed significantly reduced (corrected P < 0.05) DMN connectiv ity and altered fALFF activity in both MCI and AD groups. FDG uptake results showed hypometabolism in AD and MCI patients compared with controls. Correlations (P < 0.05) were found between WMLL and amyloid load, FDG uptake and amyloid load, as well as between amyloid load (rSUV) and fALFF. Conclusion Our quantitative results of four MRI and PET imaging metrics (fALFF/DMN, WMLL, amyloid, and FDG rSUV values) agree with published values. Signifi-cant correlations between MRI metrics, including WMLL/ functional activity and PET amyloid load suggest the potential of MRI and PET-based biomarkers for early detection of AD. PMID:24382798

  7. 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.

  8. Word Association in Early Alzheimer's Disease

    ERIC Educational Resources Information Center

    Gollan, Tamar H.; Salmon, David P.; Paxton, Jessica L.

    2006-01-01

    The hypothesis that Alzheimer's disease (AD) degrades semantic representations predicts that AD qualitatively alters spontaneous thoughts. In two experiments contrasting free associations to words with strong (e.g., "bride-groom") versus weak (e.g., "body-leg") associates participants with AD produced less common responses (e.g., "bride-pretty")…

  9. Dementia and Alzheimer's Disease in the Elderly.

    ERIC Educational Resources Information Center

    Frazier, Billie H.; Kirkland, Glenn I.

    This document contains two brief bibliographies of peer-reviewed literature, with abstracts, on dementia and Alzheimer's disease in the elderly, one written for the educator and the other for the consumer. They are two of 12 bibliographies on aging prepared by the National Agricultural Library for its "Pathfinders" series of publications. Topics…

  10. Chromatin structure in scrapie and Alzheimer's disease.

    PubMed

    McLachlan, D R; Lukiw, W J; Cho, H J; Carp, R I; Wisniewski, H

    1986-11-01

    Scrapie affected brains exhibit a number of pathological features in common with the human neurodegenerative condition, Alzheimer's disease. The present report describes studies on chromatin structure seen in these two disease processes. Chromatin associated proteins influence transcriptional activity of DNA through an effect upon chromatin structure. We examined chromatin structure by: measuring the capacity of the enzyme micrococcal nuclease to release mono- and dinucleosomes from isolated nuclei and measuring DNA-histone interactions by examining the effect of ambient tonicity upon the release of chromatin proteins. In two strains of mice infected with two strains of scrapie agent there was reduced accessibility to micrococcal nuclease and an increased content on dinucleosomes of the histone H1 and H1(0) types. These changes precede clinical signs of scrapie and resemble those found in the human conditions of Alzheimer's and Pick's disease. Scrapie mouse brain differs from Alzheimer brain in that scrapie does not alter histone-DNA interactions as monitored by ionically induced histone release from chromatin. Despite similarities, the scrapie agent appears to operate upon different molecular mechanisms than those found in Alzheimer's disease.

  11. 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. PMID:19949162

  12. Alzheimer's disease: diverse aspects of mitochondrial malfunctioning

    PubMed Central

    Santos, Renato X; Correia, Sónia C; Wang, Xinglong; Perry, George; Smith, Mark A; Moreira, Paula I; Zhu, Xiongwei

    2010-01-01

    Alzheimer's disease is a progressive neurodegenerative disorder, either assuming a sporadic, age-associated, late-onset form, or a familial form, with early onset, in a smaller fraction of the cases. Whereas in the familial cases several mutations have been identified in genes encoding proteins related with the pathogenesis of the disease, for the sporadic form several causes have been proposed and are currently under debate. Mitochondrial dysfunction has surfaced as one of the most discussed hypotheses acting as a trigger for the pathogenesis of Alzheimer's disease. Mitochondria assume central functions in the cell, including ATP production, calcium homeostasis, reactive oxygen species generation, and apoptotic signaling. Although their role as the cause of the disease may be controversial, there is no doubt that mitochondrial dysfunction, abnormal mitochondrial dynamics and degradation by mitophagy occur during the disease process, contributing to its onset and progression. PMID:20661404

  13. 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.

  14. 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.

  15. 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

  16. Beyond amyloid: getting real about nonamyloid targets in Alzheimer's disease.

    PubMed

    Herrup, Karl; Carrillo, Maria C; Schenk, Dale; Cacace, Angela; Desanti, Susan; Fremeau, Robert; Bhat, Ratan; Glicksman, Marcie; May, Patrick; Swerdlow, Russell; Van Eldik, Linda J; Bain, Lisa J; Budd, Samantha

    2013-07-01

    For decades, researchers have focused primarily on a pathway initiated by amyloid beta aggregation, amyloid deposition, and accumulation in the brain as the key mechanism underlying the disease and the most important treatment target. However, evidence increasingly suggests that amyloid is deposited early during the course of disease, even prior to the onset of clinical symptoms. Thus, targeting amyloid in patients with mild to moderate Alzheimer's disease (AD), as past failed clinical trials have done, may be insufficient to halt further disease progression. Scientists are investigating other molecular and cellular pathways and processes that contribute to AD pathogenesis. Thus, the Alzheimer's Association's Research Roundtable convened a meeting in April 2012 to move beyond amyloid and explore AD as a complex multifactorial disease, with the goal of using a more inclusive perspective to identify novel treatment strategies. PMID:23809366

  17. 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.

  18. Circulating Biomarker Panels in Alzheimer's Disease.

    PubMed

    Zafari, Sachli; Backes, Christina; Meese, Eckart; Keller, Andreas

    2015-01-01

    The early diagnosis of diseases frequently represents an important unmet clinical need supporting in-time treatment of pathologies. This also applies to neurodegenerative diseases such as Alzheimer's disease (AD), the most common form of dementia, estimated to affect millions of individuals worldwide. The respective diagnostic and prognostic markers, especially for the preclinical stages of AD, are expected to improve patients' outcome significantly. In the last decades, many approaches to detecting AD have been developed, including markers to discover changes in amyloid-β levels [from cerebrospinal fluid (CSF) or using positron emission tomography] or other brain imaging technologies such as structural magnetic resonance imaging (MRI), functional-connectivity MRI or task-related functional MRI. A major challenge is the detection of AD using minimally or even noninvasive biomarkers from body fluids such as plasma or serum. Circulating biomarker candidates based on mRNAs or proteins measured from blood cells, plasma or serum have been proposed for various pathologies including AD. As for other diseases, there is a tendency to use marker signatures obtained by high-throughput approaches, which allow the generation of profiles of hundreds to thousands of biomarkers simultaneously [microarrays, mass spectrometry or next-generation sequencing (NGS)]. Beyond mRNAs and proteins, recent approaches have measured small noncoding RNA (so-called microRNA) profiles in AD patients' blood samples using NGS or array-based technologies. Generally, the development of marker panels is in its early stages and requires further, substantial clinical validation. In this review, we provide an overview of different circulating AD biomarkers, starting with a brief summary of CSF markers and focusing on novel biomarker signatures such as small noncoding RNA profiles.

  19. Genetic determinants of disease progression in Alzheimer's disease.

    PubMed

    Wang, Xingbin; Lopez, Oscar L; Sweet, Robert A; Becker, James T; DeKosky, Steven T; Barmada, Mahmud M; Demirci, F Yesim; Kamboh, M Ilyas

    2015-01-01

    There is a strong genetic basis for late-onset Alzheimer's disease (LOAD); thus far 22 genes/loci have been identified that affect the risk of LOAD. However, the relationships among the genetic variations at these loci and clinical progression of the disease have not been fully explored. In the present study, we examined the relationships of 22 known LOAD genes to the progression of AD in 680 AD patients recruited from the University of Pittsburgh Alzheimer's Disease Research Center. Patients were classified as "rapid progressors" if the Mini-Mental State Examination (MMSE) changed ≥3 points in 12 months and "slow progressors" if the MMSE changed ≤2 points. We also performed a genome-wide association study in this cohort in an effort to identify new loci for AD progression. Association analysis between single nucleotide polymorphisms (SNPs) and the progression status of the AD cases was performed using logistic regression model controlled for age, gender, dementia medication use, psychosis, and hypertension. While no significant association was observed with either APOE*4 (p = 0.94) or APOE*2 (p = 0.33) with AD progression, we found multiple nominally significant associations (p < 0.05) either within or adjacent to seven known LOAD genes (INPP5D, MEF2C, TREM2, EPHA1, PTK2B, FERMT2, and CASS4) that harbor both risk and protective SNPs. Genome-wide association analyses identified four suggestive loci (PAX3, CCRN4L, PIGQ, and ADAM19) at p < 1E-05. Our data suggest that short-term clinical disease progression in AD has a genetic basis. Better understanding of these genetic factors could help to improve clinical trial design and potentially affect the development of disease modifying therapies.

  20. Immunolocalization of Kisspeptin Associated with Amyloid-β Deposits in the Pons of an Alzheimer's Disease Patient.

    PubMed

    Chilumuri, Amrutha; 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.

  1. 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.

  2. The music therapy assessment tool in Alzheimer's patients.

    PubMed

    Glynn, N J

    1992-01-01

    1. Empirical research is needed to evaluate immediate and sustained physiological, psychological, and psychosocial therapeutic effects, if any, of music therapy on behavioral patterns of elderly institutionalized Alzheimer's patients. 2. The Music Therapy Assessment Tool (MTAT) was specifically designed and developed to assess the effects of music therapy on behavioral patterns of Alzheimer's disease patients. 3. Preliminary testing of the MTAT suggests that it has fairly high internal consistency and inter-rater reliability and warrants consideration as a research tool. 4. Musical intervention included familiar music to facilitate communication and socialization, ethnic and nostalgic music to stimulate reminiscence, and melodies with distinctive rhythmic patterns to enhance movement and behavioral repatterning.

  3. In vivo target bio-imaging of Alzheimer's disease by fluorescent zinc oxide nanoclusters.

    PubMed

    Lai, Lanmei; Zhao, Chunqiu; Su, Meina; Li, Xiaoqi; Liu, Xiaoli; Jiang, Hui; Amatore, Christian; Wang, Xuemei

    2016-07-21

    Alzheimer's disease (AD) is an irreversible neurodegenerative disease which is difficult to cure. When Alzheimer's disease occurs, the level of zinc ions in the brain changes, and the relevant amount of zinc ions continue decreasing in the cerebrospinal fluid and plasma of Alzheimer's patients with disease exacerbation. In view of these considerations, we have explored a new strategy for the in vivo rapid fluorescence imaging of Alzheimer's disease through target bio-labeling of zinc oxide nanoclusters which were biosynthesized in vivo in the Alzheimer's brain via intravenous injection of zinc gluconate solution. By using three-month-old and six-month-old Alzheimer's model mice as models, our observations demonstrate that biocompatible zinc ions could pass through the blood-brain barrier of the Alzheimer's disease mice and generate fluorescent zinc oxide nanoclusters (ZnO NCs) through biosynthesis, and then the bio-synthesized ZnO NCs could readily accumulate in situ on the hippocampus specific region for the in vivo fluorescent labeling of the affected sites. This study provides a new way for the rapid diagnosis of Alzheimer's disease and may have promising prospects in the effective diagnosis of Alzheimer's disease.

  4. [Alzheimer's disease and diabetes - the common pathogenesis].

    PubMed

    Halmos, Tamas; Suba, Ilona

    2016-03-01

    Epidemiological studies presented evidence that Alzheimer's disease and type 2 diabetes share common features in their pathophysiology and clinical patterns. Insulin resistance is a characteristic feature of both diseases. According to the pathomechanism, inflammatory, metabolic, and an atypical form based on the deficiency of zinc ions can be distinguished. Glucose metabolic disorders, related to Alzheimer's disease, are type 2 diabetes, and prediabetes/metabolic syndrome. Based on the common pathophysiological patterns of these two diseases, Alzheimer's disease is customary called type 3 diabetes. In the research on dementias, insulin resistance stands in the highlight for its documented harmful effects on cognitive function and causes dementia. Insulin-like growth factor also influences cognitive functions. Reduced input of this hormone into the brain may also cause dementia, however literary data are controversial. In Alzheimer's disease, deposition of amyloid ß in the brain, hyperphosphorylation of tau proteins and dysruption of neurofibrilles are characteristic. Amyloid ß is co-secreted in the ß-cells of the pancreas with insulin. Amyloid ß and hyperphosphorylated tau protein were detected in the Langerhans islets by autopsy. Amyloid deposits, found in the pancreas and brain presented similarities. As a consequence of hyperglycemia, glycation endproducts cause the development of amyloid plaques, dysruption of neurofibrilles, and activated microglia, all are typical to Alzheimer's disease. Continuous hyperglycemia leads to oxidative stress, which used to play significant role in the development of both diseases. Low-grade inflammation is also a significant pathophysiological factor in both disorders. The sources of inflammation are proinflammatorical adipocytokines, dysbacteriosis, metabolic endotoxaemia, caused by lipopolysaccharides, and high fat diet which also lead to insulin resistance. Based on recent data, microbial amyloid, the main product of

  5. 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

  6. 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.

  7. Deregulation of sphingolipid metabolism in Alzheimer's disease

    PubMed Central

    He, Xingxuan; Huang, Yu; Li, Bin; Gong, Cheng-Xing; Schuchman, Edward H.

    2010-01-01

    Abnormal sphingolipid metabolism has been previously reported in Alzheimer's disease (AD). To extend these findings, several sphingolipids and sphingolipid hydrolases were analyzed in brain samples from AD patients and age-matched normal individuals. We found a pattern of elevated acid sphingomyelinase (ASM) and acid ceramidase (AC) expression in AD, leading to a reduction in sphingomyelin and elevation of ceramide. More sphingosine also was found in the AD brains, although sphingosine-1-phosphate (S1P) levels were reduced. Notably, significant correlations were observed between the brain ASM and S1P levels and the levels of amyloid beta peptide (Aβ) and phosphorylated tau protein. Based on these findings, neuronal cell cultures were treated with Aβ oligomers, which were found to activate ASM, increase ceramide, and induce apoptosis. Pre-treatment of the neurons with purified, recombinant AC prevented the cells from undergoing Aβ-induced apoptosis. We propose that ASM activation is an important pathological event leading to AD, perhaps due to Aβ deposition. The downstream consequences of ASM activation are elevated ceramide, activation of ceramidases, and production of sphingosine. The reduced levels of S1P in the AD brain, together with elevated ceramide, likely contribute to the disease pathogenesis. PMID:18547682

  8. Early neuropsychological detection of Alzheimer's disease.

    PubMed

    Bastin, C; Salmon, E

    2014-11-01

    Lifestyle modification offers a promising way of preventing or delaying Alzheimer's disease (AD). In particular, nutritional interventions can contribute to decrease the risk of dementia. The efficacy of such interventions should be assessed in individuals thought to be prone to AD. It is therefore necessary to identify markers that may help detecting AD as early as possible. This review will focus on subtle neuropsychological changes that may already exist in the predementia phase, and that could point to individuals at risk of dementia. Episodic memory decline appears consistently as the earliest sign of incipient typical AD. An episodic memory test that ensures deep encoding of information and assesses retrieval with free as well as cued recall appears as a useful tool to detect patients at an early stage of AD. Beyond the memory domain, category verbal fluency has been shown to decline early and to predict progression to AD. Moreover, in line with current diagnosis criteria for prodromal AD, combining neuropsychological scores and neuroimaging data allows a better discrimination of future AD patients than neuroimaging or neuropsychological data alone. Altogether, the detection of cognitive changes that are predictive of the typical form of probable AD already in the predementia stage points to at risk people who are the best target for therapeutic interventions, such as nutrition or physical exercise counseling or dietary interventions. PMID:25182019

  9. [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. PMID:26009241

  10. Apathy in Alzheimer's Disease: Any Effective Treatment?

    PubMed Central

    Fasanaro, Angiola M.

    2014-01-01

    Objective. This review has evaluated the effectiveness of pharmacological treatment of apathy in patients with Alzheimer's disease (AD). Methods. A systematic literature search was conducted on published clinical trials assessing the effects of pharmacological treatment on apathy in AD over the last 10 years. Results. Fourteen studies considered of good quality were included in the analysis (4 randomized controlled trials, 9 open-label studies, and 1 retrospective analysis). Cholinesterase inhibitors were investigated in 9 studies, monoaminergic compounds such as methylphenidate and modafinil in two trials and one trial, respectively, and Ginkgo biloba (EGb 761 extract) and citalopram in one study each. Cholinesterase inhibitors did not show statistical significant effect in 1 RCT study but were associated to improvement in 3 open-label studies. Methylphenidate elicited a small but significant activity accompanied by relevant side effects such as high blood pressure, cough, and osteoarticular pain. EGb 761 was well tolerated and countered apathy. Other treatments induced modest improvements or were ineffective. Conclusions. Apathy treatment remains a challenge and there is no evident advantage of any specific pharmacotherapy tested so far. The development of controlled studies according to updated guidelines for the diagnosis of apathy in patients with AD is desirable. PMID:24672318

  11. Alzheimer disease: current concepts & future directions.

    PubMed

    Musiek, Erik S; Schindler, Suzanne E

    2013-01-01

    Alzheimer disease (AD) is the most common cause of dementia in individuals over age 65, and is expected to cause a major public health crisis as the number of older Americans rapidly expands in the next three decades. Herein, we review current strategies for diagnosis and management of AD, and discuss ongoing clinical research and future therapeutic directions in the battle against this devastating disease.

  12. Cortical metabolism, acetylcholinesterase staining and pathological changes in Alzheimer's disease.

    PubMed

    McGeer, E G; McGeer, P L; Kamo, H; Tago, H; Harrop, R

    1986-11-01

    The local cerebral metabolic rate for glucose (LCMRgl) was determined by positron emission tomography (PET) using the 18F-fluorodeoxyglucose method in a series of Alzheimer patients and normal controls. The LCMRgl declined in the cerebral cortex with age, but the decrement was significantly greater in the clinically diagnosed Alzheimer's cases. Comparison of PET and psychological data indicated that, as the disease progressed clinically, the reduction in cortical LCMRgl and the number of cortical regions involved also increased. Variable regions of cortex were involved in the early stages but the temporal, parietal and frontal regions were most typically affected. One case coming to autopsy showed that the severity of the LCMRgl decline paralleled loss of neurons in the cortex and their replacement with astroglia. A case of Pick's disease coming to autopsy had shown a different and highly characteristic pattern of cortical metabolic defect. In this case also a poor metabolic rate was associated with extensive g